<<

USOO8647676B2

(12) United States Patent (10) Patent No.: US 8,647,676 B2 Nygaard et al. (45) Date of Patent: Feb. 11, 2014

(54) ANTIMICROBIAL COMPOSITION FROM Haug, T. et al., “Antibacterial activity in four marine crustacean COPEPODS decapods'; Fish & Shelfish Immunology, 12, pp. 371-385; 2002. (75) Inventors: Halvor Nygaard, Bones (NO): Eyolf Kattner et al; "Lipid composition of Calanus finmarchicus from the Langmyhr, Bergen (NO) north Sea and the arctic. A comparative study; Comp. Biochem and Physiol, vol. 94, No. 1, pp. 185-188, 1989. (73) Assignee: Nofima Ingrediens, Fyllingsdalen (NO) Khattab Rafat MA. etal; "Screening for antibacterial and antifungal activities in some selected marine organisms of the Suez Canal and (*) Notice: Subject to any disclaimer, the term of this Red Sea.”: Egypt. J. Exp. Biol. (Zool.), vol. 4; pp. 223-228; 2008. patent is extended or adjusted under 35 Li C. et al.; "Strongylocins, novel antimicrobial peptides from the U.S.C. 154(b) by 354 days. green sea urchin, Strongylocentrotus droebachiensis.'; Dev. Comp. Immunol., vol. 32(12); pp. 1430-1440; 2008. (21) Appl. No.: 13/124,756 Marcus N. H. et al.; "A guide to the meso-scale production of the copecod Acartia tonsa.; Florida Sea Grant, http://www.filseagrant. (22) PCT Filed: Oct. 28, 2009 org/program areas/aquaculture? copepod/index.htm, 2007. R. M. Bond; “Digestive enzymes of the pelagic copepod, Calanus (86). PCT No.: PCT/EP2009/064229 finmarchicus'; Biol. Bull. Mar. Biol. Labs (Woods hole, Mass.), 67. pp. 461–465; 1934. S371 (c)(1), Smith V. J. et al.; “Crustins: Enigmatic WAP domain-containing (2), (4) Date: Jul. 6, 2011 antibacterial proteins from crustaceans'; Developm, and Comp. Immunol. 32: pp. 758-772; 2008. (87) PCT Pub. No.: WO2010/049454 Solgaard G. et al., “Proteolytic activities and protease classes in the PCT Pub. Date: May 6, 2010 Zooplankton Calanus finmarchicus'; Comp. Biochem and Physiology, part B 147, pp. 475-481, 2007. (65) Prior Publication Data Sperstad SV, et al.; "Characterization of crustins from the hemocytes US 2011 FO256232A1 Oct. 20, 2011 of the spider crab, Hyasaraneus, and the red king crab, Paralithodes camtschaticus.”: Dev. Comp. Immunol. vol. 33(4); pp. 583-581; (30) Foreign Application Priority Data 2009. Stensvág K. et al.; "Arasin 1, a proline-arginine-rich antimicrobial Oct. 28, 2008 (NO) ...... 20084555 peptide isolated from the spider crab, Hyasaraneus.”: Dev. Comp. Immunol., vol. 32(3): pp. 275-285; 2008. (51) Int. Cl. Strom et al; "Biosynthesis off trimethylamine oxide in Calanus A6 IK 35/56 (2006.01) finmarchicus. Properties of a soluble trimethylamine A6IP3/04 (2006.01) monooxygenase'; Comp Biochem and Physiol, vol. 65, No. 2, pp. 243-249, 1980. (52) U.S. Cl. Yusuf A. A. et al.; "Seasonal Variations in the Physical Characteristics USPC ...... 424/520; 514/2.4 of the Copecod Calanus finmarchicus (Gunnerus) Along the North (58) Field of Classification Search Atlantic.”; Journ. Biol. Sciences, vol. 8(1); pp. 95-100; 2008. USPC ...... 424/520; 514/2.4 See application file for complete search history. Primary Examiner — Rosanne Kosson (56) References Cited (74) Attorney, Agent, or Firm — Gifford, Krass, Sprinkle, U.S. PATENT DOCUMENTS Anderson & Citkowski, P.C. 2009, O1301.49 A1 5, 2009 Raa et al. (57) ABSTRACT FOREIGN PATENT DOCUMENTS The present invention relates to an antimicrobial composi tion, and to a process for the preparation of Such a composi WO WO 2009/067020 5, 2009 tion. The invention also relates to the use of Such an antimi OTHER PUBLICATIONS crobial composition. The present invention further relates to the use of the antimicrobial composition as a pharmaceutical. Destoumieux D, et al.; “Penaeidins, a family of antimicrobial peptides from penaeid Schrimp (Crustacea, Decapoda)”; CMLS; Cell. Mol Life Sci. 57, pp. 1260-1271, 2000. 16 Claims, 12 Drawing Sheets U.S. Patent US 8,647,676 B2

eÐpeqsnup U.S. Patent US 8,647,676 B2

(sunou)au?L U.S. Patent Feb. 11, 2014 Sheet 3 of 12 US 8,647,676 B2

o m

5 S s .9 C

t

E. - -E=a-s-E-L-

------...--

th (uug() AllSuelu U.S. Patent Feb. 11, 2014 Sheet 4 of 12 US 8,647,676 B2

e

s

s s 3. S s

S

s U.S. Patent Feb. 11, 2014 Sheet 5 of 12 US 8,647,676 B2

8

R

S

s i i U.S. Patent Feb. 11, 2014 Sheet 6 of 12 US 8,647,676 B2

S

S

s S S 3. U.S. Patent Feb. 11, 2014 Sheet 7 of 12 US 8,647,676 B2

N

O

N ----- e r N In in C N es U.S. Patent Feb. 11, 2014 US 8,647,676 B2

·------…:…···---···---·····H··

Tyrres 1- is "serrierrerrrrrrrrrr.

r L o s .

gzeu Jo

U.S. Patent Feb. 11, 2014 Sheet 9 of 12 US 8,647,676 B2

6(61-)

sdo "Aisuelu U.S. Patent Feb. 11, 2014 Sheet 10 of 12 US 8,647,676 B2

rócz

v?dz

Staffy sueyu U.S. Patent US 8,647,676 B2

sdo "A Sueu U.S. Patent Feb. 11, 2014 Sheet 12 of 12 US 8,647,676 B2

US 8,647,676 B2 1. 2 ANTMICROBAL COMPOSITION FROM and to the use of a composition obtained from Calanus fin COPEPODS marchicus in the treatment of microbial in an indi vidual in need thereof. CROSS-REFERENCE TO RELATED APPLICATIONS DEFINITIONS This application is the U.S. National Phase of PCT/ The term proteinaceous is defined as any molecule com EP2009/064229 filed Oct. 28, 2009, which claims priority of prising amino acids connected by amide (peptide) bonds. Norwegian Patent Application 20084555 filed Oct. 28, 2008. Non-proteinaceous is any molecule, which does not comprise 10 amino acids connected by amide (peptide) bonds. All patent and non-patent references cited in the present A protein in the present context is an organic macromol application, are also hereby incorporated by reference in their ecule made of amino acids. A protein is a biopolymer. Pro entirety. teins consist of one or more polypeptide molecules. The norwegian patent application 20084555 and the refer A peptide in the present context is defined as a molecule ences cited herein are hereby incorporated in the patent appli 15 consisting of 2 or more amino acids. Peptides are Smaller than cation in its entirety. proteins. The dividing line between a peptide and a protein/ polypeptide is at about 50 amino acids. Depending on the FIELD OF INVENTION number of amino acids, peptides are called dipeptides, trip eptides, tetrapeptides, and so on. The present invention relates to an antimicrobial composi A nucleotide is composed of a nucleobase (nitrogenous tion obtained from the marine copepod Calanus finnarchi base), a five-carbon sugar (either ribose or 2'-deoxyribose), cus, and to a process for the preparation of Such a composi and one to three phosphate groups. Together, the nucleobase tion. The invention also relates to the use of such an and Sugar comprise a nucleoside. The phosphate groups form antimicrobial composition. bonds with either the 2, 3, or 5-carbon of the sugar, with the 25 5-carbon site most common. Ribonucleotides are nucleotides BACKGROUND OF INVENTION where the Sugar is ribose, and deoxyribonucleotides contain the Sugar deoxyribose. Nucleotides can contain either a Copepods are a group of small crustaceans found in the sea purine or pyrimidine base. Nucleic acids are polymeric mac and nearly every freshwater habitat. According to the classi romolecules made from nucleotide monomers. In DNA, the fication system of Martin and Davies (2001), the copepods 30 purine bases are adenine and guanine, while the pyrimidines form a subclass belonging to the Subphylum Crustacea (crus are thymine and cytosine. RNA uses uracil in place of thym taceans). Subphylum Crustacea is a large group of the phylum ine. Arthropoda, comprising almost 52,000 described species. Six A nucleic acid is a macromolecule or a biopolymer com classes of the Crustaceans are usually recognized. Subclass posed of chains of monomeric nucleotides. A non-nucleic Copepoda of the class Maxillopoda comprise ten orders, of 35 acid is a molecule which does not contain nucleotides. An or aerobe is an organism that can which the order Calanoida include 43 families with about Survive and grow in an oxygenated environment. Obligate 2000 species. Many species are planktonic (drifting in Sea aerobes require oxygen for aerobic cellular respiration. Fac waters), but more are benthic (living on the ocean floor), and ultative anaerobes can use oxygen, but also have anaerobic Some continental species may live in limno-terrestrial habi 40 methods of energy production. are organ tats and other wet terrestrial places, such as Swamps, under isms that may use oxygen, but only at low concentrations. leaf fall in wet forests, bogs, springs, ephemeral ponds and Aerotolerant organisms can Survive in the presence of oxy puddles, damp moss, or water-filled recesses (phytotelmata) gen, but they are anaerobic because they do not use it as a of plants such as bromeliads and pitcher plants. Many live terminal electron acceptor. underground in marine and freshwater caves, sinkholes, or 45 An anaerobic organism or anaerobe is any organism that stream beds. does not require oxygen for growth and may even die in its Two of the most abundant northern calanoid species is C. presence. There are three types: obligate anaerobes, which finnarchicus which is commonly regarded as a northern cannot use oxygen for growth and are even harmed by it; boreal species inhabiting North Atlantic Ocean, while C. aerotolerant organisms, which cannot use oxygen for growth, hyperboreus is an arctic species. 50 but tolerate the presence of it; and facultative anaerobes, The evolution of -resistant pathogenic which can grow without oxygen, but if present can utilize it. has stimulated the search for alternative antimicrobial agents A microorganism or microbe is an organism that is micro from natural sources. Antimicrobial activity has previously Scopic. been detected in several decapod crustaceans, including lob Microorganisms are very diverse; they include bacteria, ster, crabs, shrimps and freshwater crayfish. The search for 55 fungi, archaea, and protists; microscopic plants novel compounds displaying antimicrobial activity has led to (called green algae); and animals such as plankton and the the identification of several antimicrobial peptides and pro planarian. Pathogenic microorganisms cause . teins in decapod crustaceans (Haug et al., 2002). Bacteria can be classified on the basis of cell structure, cellular metabolism or on differences in cell components SUMMARY OF INVENTION 60 Such as DNA, fatty acids, pigments, antigens and quinones. By combining morphology and Gram-staining, most bacteria The present invention relates to an antimicrobial composi can be classified as belonging to one of four groups: Gram tion from a marine copepod. Such as Calanus finnarchicus, positive cocci, Gram-positive bacilli, Gram-negative cocci and to a process for the preparation of Such a composition. and Gram-negative bacilli. Bacteria can be aerobic, anaero The invention also relates to the use of such an antimicrobial 65 bic, or facultative anaerobic. composition. The present invention further relates to a phar An antimicrobial is a substance that kills or inhibits the maceutical composition obtained from Calanus finmarchicus growth of microorganisms such as bacteria, fungi, or proto US 8,647,676 B2 3 4 Zoans, as well as destroying viruses. Antimicrobial drugs trons known as a full molecular orbital. Due to the polar either kill microbes (microbicidal) or prevent the growth of nature of the water molecule itself, polar molecules are gen microbes (microbistatic). The main classes of antimicrobial erally able to dissolve in water. A non-polar compound occurs agents are (antibacterials), antivirals and antifun when there is an equal sharing of electrons between different gals targeting bacteria, viruses and fungi respectively. atoms. Examples of household non-polar compounds include The term broad-spectrum antibiotic refers to an antibiotic fats, oil and petrol/gasoline. Therefore (per the “oil and with activity against a wide range of disease-causing bacteria. water rule of thumb), most non-polar molecules are water It is also means that it acts against both Gram-positive and insoluble (hydrophobic) at room temperature. However many Gram-negative bacteria. This is in contrast to a narrow-spec non-polar organic solvents, such as turpentine, are able to trum antibiotic which is effective against only specific fami 10 lies of bacteria. dissolve polar Substances. Antiseptics are antimicrobial Substances that are applied to An infection is the colonization of a host organism by a living tissue/skin to reduce the possibility of infection, sepsis, foreign species, usually a microorganism. In an infection, the or putrefaction. infecting organism seeks to utilize the host’s resources to A preservative is a compound that is added to products such 15 multiply, usually at the expense of the host. The infecting as foods, pharmaceuticals, paints, biological samples, wood, organism, or , interferes with the normal functioning etc. to prevent decomposition by microbial growth or by of the host. Primary and secondary infection may either refer undesirable chemical changes. to Succeeding infections or different stages of one and the Disinfectants are antimicrobial agents that are applied to same infection. non-living objects to destroy microorganisms, the process of A fungus is any member of a large group of eukaryotic which is known as disinfection. Disinfection may be defined organisms that includes microorganisms such as yeasts and as: Cleaning an article of some or all of the pathogenic organ molds, as well as the more familiar mushrooms. isms which may cause infection. An antifungal is defined as any compound capable of kill Small molecules are low molecular weight organic com ing or inhibiting the growth of a fungus. pounds, which by definition are not polymers. The upper 25 Anti-fouling: The effect of controlling, reducing and/or molecular weight limit for a small molecule is approximately eliminating over time the number of undesirable microorgan 1000 Daltons (Da). Biopolymers such as nucleic acids, pro isms in a bio-film. teins, and polysaccharides (such as starch or cellulose) are not Bio-film: Habitation of microbial organisms on a solid or Small molecules. Very Small oligomers are also usually con semi-solid Surface. sidered Small molecules, such as dinucleotides, Small pep 30 Resistance or drug resistance is the reduction in effective tides such as the antioxidant glutathione, and disaccharides ness of a drug in curing a disease or improving a patients such as sucrose. One group of small molecules are known as secondary metabolites. symptoms. When the drug is not intended to kill or inhibit a Secondary metabolites are Small organic compounds of pathogen, then the term is equivalent to dosage failure or drug metabolism that are not directly involved in the normal 35 tolerance. More commonly, the term is used in the context of growth, development, or reproduction of organisms. diseases caused by . Pathogens are said to be drug A biomolecule is any organic molecule that is produced by resistant when drugs meant to neutralize them have reduced a living organism, including large polymeric molecules Such effect. When an organism is resistant to more than one drug, as proteins, polysaccharides, and nucleic acids as well as it is said to be multi-resistant. Drug resistance is an example Small molecules Such as primary metabolites, secondary 40 of evolution in microorganisms. Individuals that are not Sus metabolites, and natural products. ceptible to the drug effects are capable of Surviving drug Organic compounds are molecules that contain carbon treatment, and therefore have greater fitness than Susceptible with the exception of a few types of compounds such as individuals. By the process of natural selection, drug resistant carbonates, simple oxides of carbon and cyanides, as well as traits are selected for in Subsequent offspring, resulting in a the allotropes of carbon, which are considered inorganic. 45 population that is drug resistant. They can be either natural or synthetic organic compounds. A gel is a semirigid colloidal dispersion of a solid prefer Based upon the size of organic compounds, they can be clas ably with a liquid. A gel can further be defined as a solid, sified as either Small molecules or polymers. jelly-like material that can have properties ranging from Soft A solvent is a liquid, Solid, or gas that dissolves another and weak to hard and tough. Gels are defined as a Substan Solid, liquid, or gaseous Solute, resulting in a solution. The 50 tially dilute crosslinked system, which exhibits no flow when most common solvent in everyday life is water. in the steady-state. Chemical Polarity refers to a separation of electric charge A lotion is a low- to medium-viscosity, topical preparation leading to a molecule having an electric dipole. Polar mol intended for application to unbroken skin; creams and gels ecules can bond together due to dipole-dipole intermolecular have a higher viscosity than lotions. forces between one molecule (or part of a large molecule) 55 with asymmetrical charge distribution and another molecule BRIEF DESCRIPTION OF DRAWINGS also with asymmetrical charge distribution. Molecular polar ity is dependent on the difference in electronegativity FIG. 1. shows the phylogeny of the Crustacea. between atoms in a compound and the asymmetry of the FIG. 2. shows the Development of the number of viable compounds structure. For example, a molecule of water is 60 Salmonella berta cells. polar because of the unequal sharing of its electrons in a FIG. 3. HPLC-chromatogram of the anion exchange “bent' structure, whereas methane is considered non-polar eXtract. because the carbon shares the electrons with the hydrogen FIG. 4. Comparison of analytic chromatography of early atoms uniformly. A molecule may be polar either as a result of fractions re-chromatographed on a conventional C18 (left), or polar bonds due to differences in electronegativity as 65 polar endcapped C18 (right). described above, or as a result of an asymmetric arrangement FIG. 5. Chromatogram of the semipreparativ C18-purifi of non-polar covalent bonds and non-bonding pairs of elec cation. US 8,647,676 B2 5 6 FIG. 6. Isocratic normal phase chromatography of the bio In addition to C. finnarchicus, species of Calanus include: active fraction from the semi-preparative reversed phase puri Calanus brevicornis, Calanus glacialis, Calanus helgolandi fication (FIG. 5). cus, Calanus hyperboreus, Calanus marshallae, Calanus FIG. 7. Isocratic normal phase chromatography of the pacificus, Calanus propinquus, Calanus simillimus, Calanus active peak from the semi-preparative reversed phase frac 5 S.C.S. tionation (FIG. 5). Methods for Obtaining the Antimicrobial Composition from FIG. 8. UV-spectra of the various peaks from the normal C. finnarchicus phase chromatography shown in FIG. 7. The antimicrobial composition of the present invention can FIG.9. MS-analysis of fraction 4 from FIG. 8. be prepared form C. finmarchicus by any method suitable for FIG. 10. MSMS-analysis of the 245-ion. 10 obtaining a composition with antimicrobial activity from C. finnarchicus. FIG. 11. MSMS-analysis of the 347-ion. In one embodiment the present invention relates to a pro FIG. 12. The structure of penostatin with a mass=346 Da. cess for producing a composition comprising one or more DETAILED DESCRIPTION OF THE INVENTION antimicrobial compounds, said process comprising the steps 15 of: i) providing a sample comprising C. finnarchicus or parts The present invention was discovered through the Surpris of C. finmarchicus, ing observation that samples of the marine copepod Calanus ii) performing one or more purification steps and/or isola finnarchicus (crustacea) could be stored for several days at tion steps and/or concentration steps resulting in purifi ambient temperature without developing off-odors or other cation and/or isolation and/or concentration from said signs of spoilage. Furthermore, it was observed that the sample of a composition comprising one or more anti samples did not contain bacteria detectable by the standard microbial compounds, wherein at least Some of said methods for enumeration of aerobic micro-organisms, and antimicrobial compounds are preferably non-proteina that an extract from Calanus finmarchicus possesses antimi ceous and non-nucleic acid antimicrobial compounds. crobial activity directed against various bacterial strains and 25 The purpose of the purification step is the removal of unde Some fungi. sirable substances. Undesirable substances in the present Another copepod species, C. hyperboreus, was also inves context are any substances that do not contribute directly or tigated for antimicrobial activity. Antimicrobial activity was indirectly to the antimicrobial effect of the composition. not detected in the C. hyperboreus, suggesting that the anti Undesirable substances can be, but are not limited to salts, microbial activity discovered in C. finmarchicus extracts is 30 natural environmental compounds, structural elements of the specific for this species of Calanus copepods. copepods not exhibiting antimicrobial activity, etc. In one The present invention thus relates in one embodiment to an embodiment purification can be performed by dividing the antimicrobial composition, wherein the composition is sample into two or more fractions or phases and discarding obtained from copepods, such as Calanus species, particu the fraction or phase not comprising the antimicrobial com 35 position. larly the marine copepod Calanus finnarchicus. The purpose of the isolation step is to retain desirable In the present invention the antimicrobial composition Substances. Desirable Substances in the present context are comprises one or more identical or different antimicrobial any substances that directly or indirectly contribute to the compounds. antimicrobial effect of the composition. The isolation can be In one embodiment the antimicrobial composition com 40 performed by isolating or separating the one or more antimi prises a single antimicrobial compound. crobial compounds according to chemical and/or physical In other embodiments the antimicrobial composition com properties. Examples of chemical properties include affinity prises two or more different antimicrobial compounds. Such for one or more compounds and chemical stability. Examples as three, for example four, Such as five, for example six, Such of physical properties include mass or size, charge, Solubility, as seven, for example eight, Such as nine, for example ten 45 polarity, distribution, melting point, boiling point and absor different antimicrobial compounds. bance. Calanus finnarchicus The purpose of the concentration step is to remove solvents Calanus is a of marine copepod in the family fully or partly to obtain a composition with a higher antimi Calanidae (Order Calanoida). Calimidae is the largest taxo crobial activity than before said concentration step was per nomic family of calanoid copepods. The genus Calanus may 50 formed. The solvent can be any liquid, wherein the one or be the most abundant animal genus on Earth. Copepods of the more antimicrobial compounds are comprised. Concentra genera Calanus and Neocalanus are ecologically important in tion can in one embodiment be performed by evaporation of the Arctic and Subarctic regions of the world’s oceans. the solvent. Calanus finnarchicus is a Zooplankton species, which is In one embodiment, an aqueous Solution comprising the found in enormous amounts in the North Sea. The body 55 antimicrobial composition is obtained by performing at least length is up to 5.4 mm for females and 3.6 mm for males. C. one physical processing step. Such as by centrifugation. finnarchicus is high in protein and contains valuable omega-3 The invention in one embodiment relates to a process for fatty acids. It contains also high amounts of antioxidant. producing an antimicrobial composition, wherein a sample Calanus finnarchicus is the dominant copepod in the north comprising C. finnarchicus is subjected to the following pro ern North Atlantic, it plays a vital role in economy of the 60 cess steps; oceans, forming middle link in food chain leading from phy i) providing a sample comprising C. finnarchicus or parts toplankton up to commercially important fish species, many of C. finmarchicus, of which feed on this species either as larvae or as adults. ii) separating said sample into at least two. Such as three Plays equally important role in global carbon cycle, since phases by centrifugation, i.e. at least two of a sediment large proportion of fixed carbon dioxide passes through oce 65 phase, an oil phase and an aqueous phase, anic food web as phytoplankton consumed by C. finnarchi iii) and isolation of said aqueous phase, wherein said aque C.S. ous phase comprises the antimicrobial composition. US 8,647,676 B2 7 8 The invention in one embodiment relates to a process for marchicus is a previously processed C. finnarchicus sample, producing an antimicrobial composition, wherein a sample Such as comprising crushed C. finnarchicus. In one embodi comprising C. finnarchicus is subjected to the following pro ment the C finnarchicus sample is a C. finnarchicus homo cess steps: genate obtained by state of the art methods. The C. finmar i) providing a sample comprising C. finnarchicus or parts chicus homogenate can in one embodiment comprise and/or of C. finmarchicus, consist of particles with an average diameter of less than 1 ii) separating said sample into at least two, such as three mm, 0.5mm, 0.25 mm, 0.1 mm, 0.05 mm and/or 0.01 mm. In phases by centrifugation, i.e. at least two of a sediment one embodiment the C. finnarchicus homogenate can be use phase, an oil phase and an aqueous phase, as an antimicrobial composition. In one embodiment the C. iii) and isolation of said sediment phase, wherein said 10 finnarchicus homogenate is used for treatment of an indi sediment phase comprises the antimicrobial composi vidual in need thereof. tion. In one embodiment, the sample comprising whole C. fin The invention in one embodiment relates to a process for marchicus is dried prior to the extraction step. Drying may be producing an antimicrobial composition, wherein a sample performed in any suitable way. In a preferred embodiment the comprising C. finnarchicus is subjected to the following pro 15 drying is performed by freeze-drying. Other drying methods cess steps: may be used Such as e.g. heat pump drying, hot air drying, i) providing a sample comprising C. finnarchicus or parts indirect and direct steam drying. of C. finmarchicus, The extraction in step ii) above may be performed in any ii) separating said sample into at least two, such as three Suitable way. In a preferred embodiment the extraction agent phases by centrifugation, i.e. at least two of a sediment or solvent used is methanol. In other embodiments acetone phase, an oil phase and an aqueous phase, and/or ethanol may be used as the extraction agent. iii) and isolation of said oil phase, wherein said oil phase The removal of the extraction agent or solvent may in one comprises the antimicrobial composition. embodiment be performed by evaporation. The solvent may In one embodiment of the present invention, a concentrated be removed fully or partly. Evaporation of the solvent can be extract with increased antimicrobial activity as compared to 25 performed in any Suitable way known in the art. In one the antimicrobial activity of the aqueous phase is obtained by embodiment, evaporation of the solvent is performed by performing an extraction of a sample comprising C. fimmar vacuum evaporation. In another embodiment atmospheric chicus, using an extraction agent Such as methanol. evaporation is used. Accordingly, the invention in another embodiment relates The concentrated extract obtained in step iv) above can be to a process for the isolation or extraction of an antimicrobial 30 dissolved in any suitable solvent. In one embodiment, the composition, wherein a sample comprising C. finnarchicus is Solvent is an aqueous solvent. In a preferred embodiment of subjected to the following method steps: the present invention, the solvent is water, more preferred i) providing a sample comprising C. finnarchicus or parts deionised water. of C. finmarchicus, In one embodiment, the antimicrobial composition is ii) extracting said sample using one or more extraction 35 obtained by a process comprising a step of deproteinisation, agents, i.e. removing proteinaceous compounds from the composi iii) removing said one or more extraction agents to obtain a tion. In one example the deproteinisation could be performed concentrated extract, and optionally by a method comprising the step of acetone precipitation iv) dissolving the concentrated extract, and/or salting out. Salting out is a method of separating pro thereby obtaining a concentrated antimicrobial composition 40 teins based on the principle that proteins are less soluble at comprising one or more antimicrobial compounds. high salt concentrations. The salt concentration needed for The invention in another embodiment relates to a process the protein to precipitate out of the solution differs from for the isolation or extraction of an antimicrobial composi protein to protein. Dialysis can be used to remove the salt if tion, wherein a sample comprising C. finnarchicus is Sub needed. jected to the following method steps: 45 In one embodiment, the preparation of the antimicrobial i) providing a sample comprising C. finnarchicus or parts composition according to the present invention further com of C. finmarchicus, prises the step offiltering the obtained solution containing the ii) extracting said sample using one or more extraction antimicrobial composition. Filtering can be performed on or agents, more times using one or more filter types. Filtering methods iii) removing said one or more extraction agents to obtain a 50 are known in the art and can for example be performed by concentrated extract, and optionally filtering through a glass fiber filter and/or a microporous iv) dissolving the concentrated extract, cellulose acetate filter or any other suitable filtering proce V) further subjecting said concentrated extract to one or dure as determined by the skilled person. In a particular more fractionation steps and/or one or more purification embodiment, a microporous cellulose acetate filter with pore steps and/or one or more isolation steps, thereby obtain 55 size 0.2 Lum is used. ing a concentrated antimicrobial composition compris According to the present invention, filtering can be per ing one or more antimicrobial compounds. The one or formed using filters selected from the group consisting of more fractionation steps and/or one or more purification purified cotton filters, glass fiber filters, paper filters and steps and/or one or more isolation steps comprises one microporous cellulose acetate filters. or more of the following steps: HPLC, Wessel-Flügge 60 In one embodiment of the present invention, the one or extraction, size exclusion, anion exchange, cation more antimicrobial compounds comprised within the antimi exchange, reversed phase chromatography, semi-pre crobial composition are further isolated by performing one or parative reversed phase chromatography. more further extraction steps. In one embodiment the sample comprising C. finnarchicus In one embodiment, the one or more further extraction step preferably comprises whole C. finmarchicus and/or whole C. 65 comprises a Wessel-Flügge extraction. finnarchicus cells and/or disrupted/degrated C. finnarchicus In one embodiment, the one or more further extraction step cells. In other embodiments the sample comprising C. fin comprises one or more chromatography steps, such as one US 8,647,676 B2 10 further chromatography extraction, for example two further a solid phase extraction (anion exchange) step, a solid chromatography extractions, such as three further chroma phase extraction (reverse phase) step; and a high pres tography extractions. sure liquid chromatography (HPLC) step (with or with In one embodiment, the further extraction step comprises a out polar end-capping); including reverse phase HPLC Solid-phase extraction, such as QMA anion exchange or and normal phase HPLC. reverse-phase column chromatography. The m/z values in a mass spectroscopical analysis of a) The present invention is also directed at the further isola from 235 to 255 mentioned above can in one embodiment be tion of the one or more antimicrobial compounds comprised from 235 to 240, and/or from 240 to 245, and/or from 245 to within the antimicrobial composition by performing one or 250, and/or 250 to 255. more chromatography steps, such as by HPLC, and selecting 10 the fractions wherein the antimicrobial activity is retained. The m/z values in a mass spectroscopical analysis of b) In one embodiment of the present invention, the antimicro from 335 to 360 mentioned above can in one embodiment be bial composition is further analysed by mass spectroscopy. from 335 to 340, and/or 340 to 345, and/or 345 to 350, and/or In one embodiment the present invention is directed to an 350 to 355 and/or 355 to 360. antimicrobial composition comprising one or more C. fin 15 Chemical Polarity of Compounds marchicus antimicrobial compounds, wherein said composi The antimicrobial composition according to the present tion is obtained or obtainable by a process comprising the invention preferably comprises one or more polar compounds steps of: exhibiting an antimicrobial activity. i) providing a sample comprising C. finnarchicus or parts The polarity of a compound is dependent on the difference thereof, in electronegativity between atoms in a compound and the ii) performing one or more purification steps and/or isola asymmetry of the compounds structure. In a non-polar com tion steps and/or concentration steps resulting in purifi pound the electrons of the molecule are distributed uniformly, cation and/or isolation and/or concentration from said whereas in a polar compound, the electrons are distributed sample of a composition comprising one or more anti asymmetrically giving rise to a molecule with an asymmetri microbial compounds, wherein at least some of said 25 cal charge distribution. antimicrobial compounds are preferably non-proteina Polarity underlies a number of physical properties includ ceous and non-nucleic acid antimicrobial compounds. ing Surface tension, Solubility, and melting- and boiling In another embodiment the present invention is directed to points. Polarity of a compound can e.g. be assessed by its an antimicrobial composition comprising one or more C. ability to dissolve inacqueous solvents, such as water. A water finnarchicus antimicrobial compounds, wherein said compo 30 soluble compound is polar, whereas a compound which is not sition is obtained or obtainable by any process mentioned in this applications. soluble in water is non-polar. The invention further relates to a method for producing one The polarity of a particular compound or composition can or more anti-microbial compounds, said method comprising be estimated by a range of different methods. the steps of: 35 In organic chemistry and the pharmaceutical Sciences, a i) providing an extractor a homogenate of C. finnarchicus, partition—(P) or distribution coefficient (D) is the ratio of and concentrations of a compound in the two phases of a mixture ii) isolating from said extract or homogenate one or more of two immiscible solvents at equilibrium. Hence these coef anti-microbial compounds, ficients are a measure of differential solubility of the com wherein said one or more anti-microbial compounds are 40 pound between these two solvents. characterised by exhibiting m/z values in a mass spec Normally one of the solvents chosen is water while the troscopical analysis of a) from 235 to 255 and/or fromb) second is hydrophobic such as octanol. Hence both the par 335 to 360, essentially as illustrated in FIG. 9. tition and distribution coefficient are measures of how hydro The compounds are preferably isolated by one or more philic (“water loving') or hydrophobic (“water fearing) a chromatographical purification steps; such as purification 45 chemical Substance is, in other words how polar a compound steps selected from, but not limited to, a Wessel-Flügge is. Partition coefficients are useful for example in estimating extraction step, a solid phase extraction (anion exchange) distribution of drugs within the body. Hydrophobic drugs step, a solid phase extraction (reverse phase) step; and a high with high partition coefficients are preferentially distributed pressure liquid chromatography (HPLC) step (with or with to hydrophobic compartments such as lipid bilayers of cells out polar end-capping); including reverse phase HPLC and 50 while hydrophilic drugs (low partition coefficients) preferen normal phase HPLC. tially are found in hydrophilic compartments such as blood The invention also relates to one or more anti-microbial S. agent(s) or a composition comprising same, said agent(s) or The partition coefficient is a ratio of concentrations of said composition being obtainable by a method comprising un-ionized compound between the two solutions. To measure the steps of: 55 the partition coefficient of ionizable solutes, the pH of the 1. providing an extractor a homogenate of C. finnarchicus, aqueous phase is adjusted Such that the predominant form of and the compound is un-ionized. The logarithm of the ratio of the 2. isolating from said extract or homogenate said one or concentrations of the un-ionized solute in the solvents is more anti-microbial compounds, called log P: wherein said one or more anti-microbial compounds are 60 characterised by exhibiting m/z values in a mass spec troscopical analysis of a) from 235 to 255 and/or fromb) solute 335 to 360, essentially as illustrated in FIG. 9. logPoctivat = lostin-ionized wherein said one or more anti-microbial compounds are Solute preferably isolated by one or more chromatographical 65 purification steps; such as purification steps selected Reverse phase HPLC can be used to estimate log P of a from, but not limited to, a Wessel-Flügge extraction step, compound and/or a composition. US 8,647,676 B2 11 12 In one embodiment of the present invention, the log P of the In one embodiment the antimicrobial composition is both one or more antimicrobial compounds in the composition of cidic and lytic. the present invention is in the range of -3 to 6, more preferred In a preferred embodiment of the present invention, the -1.5 to 4. Such as in the range of -1.5 to -1.4, for example antimicrobial composition of the present invention is bacte -1.4 to -1.3, Such as -1.3 to -1.2, for example -1.2 to -1.1, riocidic. such as -1.1 to -1.0, for example -1.0 to -0.9, such as -0.9 to In another embodiment of the present invention, the anti -0.8, for example -0.8 to -0.7, such as -0.7 to -0.6, for microbial composition of the present invention is not bacte example -0.6 to -0.5, such as -0.5 to -0.4, for example -0.4 riolytic. to -0.3, such as -0.3 to -0.2, for example -0.2 to -0.1, such The anti-fungal activity of the antimicrobial composition 10 of the present invention is either static, cidic or lytic. as -0.1 to 0.0, for example 0.0 to 0.1, such as 0.1 to 0.2, for The type of antimicrobial action of a particular compound example 0.2 to 0.3, such as 0.3 to 0.4, for example 0.4 to 0.5, or composition can be determined by several different ways such as 0.5 to 0.6, for example 0.6 to 0.7, such as 0.7 to 0.8, for known in the art. example 0.8 to 0.9, such as 0.9 to 1.0, for example 1.0 to 1.1, Characteristics of the Antimicrobial Composition such as 1.1 to 1.2, for example 1.2 to 1.3, such as 1.3 to 1.4, for 15 In one embodiment the antimicrobial composition com example 1.4 to 1.5, such as 1.5 to 1.6, for example 1.6 to 1.7, prises one or more compounds with the chemical character such as 1.7 to 1.8, for example 1.8 to 1.9, such as 1.9 to 2.0, for istics disclosed in the examples and figures of the present example 2.0 to 2.1, such as 2.1 to 2.2, for example 2.2 to 2.3, invention. such as 2.3 to 2.4, for example 2.4 to 2.5, such as 2.5 to 2.6, for In one embodiment the antimicrobial composition of the example 2.6 to 2.7, such as 2.7 to 2.8, for example 2.8 to 2.9. present invention comprises one or more antimicrobial com such as 2.9 to 3.0, for example 3.0 to 3.1, such as 3.1 to 3.2, for pounds. example 3.2 to 3.3, such as 3.3 to 3.4, for example 3.4 to 3.5, In one embodiment, the antimicrobial composition is water such as 3.5 to 3.6, for example 3.6 to 3.7, such as 3.7 to 3.8, for soluble. example 3.8 to 3.9, such as 3.9 to 4.0. In one embodiment the antimicrobial composition com In another embodiment the log Pvalue is less than 2, such 25 prises one or more polar antimicrobial compounds. as less than 1.9 for example less than 1.8, such as less than 1.7, In one embodiment, the one or more antimicrobial com for example less than 1.6, Such as less than 1.5, for example pounds of the present invention is/are heat stable. In one less than 1.4. Such as less than 1.3, for example less than 1.2, example the antimicrobial composition fully or partially Such as less than 1.1, for example less than 1.0. Such as less retains its antimicrobial activity after heating. Heating of the than 0.9, for example less than 0.8, such as less than 0.7, for 30 antimicrobial composition can be performed at 60-130°C., example less than 0.6, Such as less than 0.5, for example less such as in the range of 60-65°C., 65-70° C., 70-75°C., 75-80° than 0.4, such as less than 0.3, for example less than 0.2, such C., 80-850 C., 85-90° C.,90-950 C., 95-100° C., 100-1050 C., as less than 0.1, for example less than 0.0, Such as less than 105-110° C., 110-115° C., 115-120° C., 120-125° C., 125 -0.1, for example less than -0.2, such as less than -0.3, for 130° C. example less than -0.4, Such as less than -0.5, for example 35 In one embodiment heating is performed at about 65-75° less than -0.6, such as less than -0.7, for example less than C., more preferred at about 70° C. -0.8, such as less than -0.9, for example less than -1.0, such In one embodiment heating is performed at about 90-110 as less than -1.1, for example less than -1.2. Such as less than C., more preferred at about 100° C. -1.3. In yet another embodiment heating is performed at about Type of Action 40 120-125° C., more preferred at about 121° C. Overall, there are three types of action of antimicrobial According to the present invention, heating can be per agents: i) static action where growth is inhibited, ii) cidal formed for shorter or longer periods of time, such as from a action where organisms are killed and iii) lytic action where minute to several hours. Heating can for example be per organisms are killed and lysed. formed for a few minutes such as in the range of about 1-5 If a compound is static or biostatic, the growth of the 45 minutes, 5-10 minutes, 10-15 minutes, 15-20 minutes, 20-25 microorganism is inhibited, but it is not killed by the treat minutes, 25-30 minutes, 30 minutes-1 hour. ment. If a population of microorganisms is treated with a In a preferred embodiment, heating is performed for about static antimicrobial compound, the number of viable micro 5-20 minutes, more preferred for about 10-15 minutes. organisms is not decreased by the treatment compared to the In one embodiment heating is performed at about 65-75° total number of microorganisms. 50 C., more preferred at about 70° C. such as for about 10-15 If a compound is cidic or biocidic, the microorganism is minutes. killed by the treatment. If a population of microorganisms is In one embodiment heating is performed at about 90-110 treated with a cidic antimicrobial compound, the number of C., more preferred at about 100° C. Such as for about 10-15 viable microorganisms is decreased compared to the total minutes. number of microorganisms. 55 In yet another embodiment heating is performed at about If a compound is lytic or biolytic, the microorganism is 120-125° C., more preferred at about 121° C. such as for lysed and killed by the treatment. If a population of microor about 10-15 minutes. ganisms is treated with a lytic antimicrobial compound, both In one embodiment, the one or more antimicrobial com the number of viable and the total number of microorganisms pounds are not proteinaceous compounds, i.e. they are not is decreased to a similar extent. 60 peptides or proteins. In one example, the antimicrobial com In relation to bacteria, the terms used are bacteriostatic, position is resistant to proteolytic enzymes, thereby indicat bacteriocidic and bacteriolytic, respectively. ing that the compound does not contain amide or peptide According to the present invention the antimicrobial com bonds. position can be static, cidic or lytic. In one example, the antimicrobial composition is resistant In one embodiment the antimicrobial composition is static. 65 to pepsin treatment, meaning that the antimicrobial compo In one embodiment the antimicrobial composition is cidic. sition fully retains its antimicrobial activity following pepsin In one embodiment the antimicrobial composition is lytic. treatment. US 8,647,676 B2 13 14 In another example, the antimicrobial composition is resis than 10%, such as less than 8%, for example less than 6%, tant to alcalase treatment, meaning that the antimicrobial such as less 4%, for example less than 1%. composition fully retains its antimicrobial activity following In one embodiment the antimicrobial composition com alcalase treatment. prises less that 20% (weight/weight %) carbohydrate, for In another example, the antimicrobial composition is resis example less than 10%, such as less than 8%, for example less tant to Proteinase K treatment, meaning that the antimicrobial than 6%, such as less 4%, for example less than 1%. composition fully retains its antimicrobial activity following In one embodiment the antimicrobial composition com Proteinase K treatment. prises a compound with mass 346 and/or a m/z of 347 as In one embodiment the antimicrobial composition does not depicted in FIG. 12. 10 In one embodiment the antimicrobial composition com contain an antimicrobial compound in the form of a nucle prises a compound with UV-spectra similar or identical to the otide or nucleic acids, i.e. it is a non-nucleic acid. UV spectra depicted in FIG. 8. In one embodiment the antimicrobial composition con In one embodiment the antimicrobial composition com tains one or more antimicrobial nucleotides or nucleic acids. prises penostatin or a similar compound. In one embodiment the one or more antimicrobial com 15 Secondary Metabolites pounds are proteinaceous compounds, such as one or more Secondary metabolites, also known as natural products, are cyclic peptides. those products (chemical compounds) of metabolism that are Examples of known cyclic peptides include, but are not not essential for normal growth, development or reproduction limited to amanitins, Bacitracin, colistin, cyclosporine, of an organism. In this sense they are 'secondary'. cyclotide, dactinomycin, daptomycin, nisin, polymyxin b, Secondary metabolites, including antibiotics, are produced pristinamycin, octreotide, valinomycin. in nature and serve Survival functions for the organisms pro Carbohydrates are simple organic compounds that are ducing them. Secondary metabolites serve: (i) as competitive aldehydes or ketones with many hydroxyl groups added, usu weapons used against bacteria, fungi, amoebae, plants, ally one on each carbon atom that is not part of the aldehyde insects, and large animals; (ii) as metal transporting agents; or ketone functional group. The basic carbohydrate units are 25 (iii) as agents of symbiosis between microbes and plants, called monosaccharides. nematodes, insects, and higher animals; (iv) as sexual hor In one embodiment at least one of the one or more antimi mones; and (v) as differentiation effectors. crobial compounds of the present invention comprises a car The function or importance of these compounds to the bohydrate. organism's development is usually of ecological nature as In another embodiment at least one of the one or more 30 they are used as defence against predators (herbivores, patho antimicrobial compounds of the present invention does not gens etc.), for interspecies competition, and to facilitate the comprise a carbohydrate. reproductive processes. In one embodiment, the one or more antimicrobial com Contrary to primary metabolites these compounds are not pounds comprised within the antimicrobial composition is ubiquitous in the living organisms who produce them nor are not a strong anionic compound. 35 they necessarily expressed continuously. Although plants are In one embodiment the one or more antimicrobial com better known as a source of secondary metabolites, bacteria, pounds comprised within the antimicrobial composition is a fungi and many marine organisms (sponges, tunicates, corals, Small molecule. Snails) are very interesting Sources, too. In one embodiment the size of the one or more antimicro Secondary metabolites can be classified by their chemical bial compounds is less than 1 kDa. In other embodiments the 40 structure or physical properties into one or more of the fol size of the antimicrobial compound is less than 900 Da, for lowing groups: alkaloids, terpenoids, polyketides, aliphatic, example less than 800 Da, such as less than 700 Da, for aromatic, and heteroaromatic organic acids, phenols, iri example less than 600 Da, such as less than 500 Da, for doids, Steroids, Saponins, peptides, ethereal oils, resins and example less than 400 Da, such as less than 300 Da, for balsams. example less than 200 Da, such as less than 100 Da. 45 In one embodiment of the present invention at least one of In other embodiments, the size of the one or more antimi the one or more antimicrobial compounds comprises or con crobial compounds comprised within the antimicrobial com sists of a secondary metabolite Such as one or more com position is in the range of 100 Da-1 kDa, such as 100-200 Da. pounds selected from the group consisting of alkaloids, ter for example 200-300 Da, such as 300-400 Da, for example penoids, polyketides, aliphatic, aromatic, and heteroaromatic 400-500 Da, such as 500-600 Da, for example 700-800 Da. 50 organic acids, phenols, iridoids, Steroids, Saponins, peptides, such as 800-900 Da, for example 900-1000 Da (1 kDa). ethereal oils, resins and balsams. In other embodiments the size of the one or more antimi Industrial Uses of the Antimicrobial Composition from C. crobial compounds is close to 1 kDa, but not necessarily less finnarchicus than 1 kDa, for example less than 1.1 kDa, such as less than Antiseptics 1.2 kDa, for example less than 1.3 kDa, such as less than 1.4 55 In one embodiment the antimicrobial composition is an kDa, for example less than 1.5 kDa, such as less than 1.6 kDa, antiseptic. Antiseptics are antimicrobial Substances that are for example less than 1.7 kDa, such as less than 1.8 kDa. applied to living tissue/skin to reduce the possibility of infec In one embodiment the antimicrobial composition com tion and/or sepsis, and/or putrefaction. Antiseptics are gener prises less that 20% (weight/weight%) protein, for example ally distinguished from antibiotics by their ability to be trans less than 10%, such as less than 8%, for example less than 6%, 60 ported through the lymphatic system to destroy bacteria such as less 4%, for example less than 1%. within the body, and from disinfectants, which destroy micro In one embodiment the antimicrobial composition com organisms found on non-living objects. prises less that 20% (weight/weight%) ash, for example less The microbial composition according to the present inven than 10%, such as less than 8%, for example less than 6%, tion can be a true germicides, capable of destroying microbes such as less 4%, for example less than 1%. 65 (bacteriocidal), or bacteriostatic and only prevent or inhibit In one embodiment the antimicrobial composition com their growth. Antibacterials are antiseptics that have the prises less that 20% (weight/weight%) lipid, for example less proven ability to act against bacteria especially if they target US 8,647,676 B2 15 16 systems which kill only bacteria. Microbicides which kill shown to retard the seawater flow through the pipe and has to particles are called viricides or antivirals. The antimi be removed with the tube cleaning process. crobial composition of the present invention can be a true In one preferred embodiment the surface for application of germicide, an antibacterial, a microbicide, a viricide and/or the anti-fouling composition is a Surface that is at least occa an antiviral. sionally immersed in water, wherein said water includes Disinfectant fresh, salt or brackish water. The surface can be selected from In one embodiment the antimicrobial composition is a the group consisting of the Surfaces of vessels including boats disinfectant. In one embodiment the antimicrobial composi and ships, ship hulls, off-shore equipment, pipes, Substruc tion can be used in cleaning of hospitals such as in cleaning of tures of bridges, piers and aquacultural apparatuses including an operating room and/or Surgery equipment. 10 fish farming nets. Disinfectants should generally be distinguished from anti The methods and compositions disclosed herein may be biotics that destroy microorganisms within the body, and used on a variety of surfaces, including but not limited to boat from antiseptics, which destroy microorganisms on living hulls, marine markers, bulkheads, pilings, water inlets, floors, tissue. Sanitizers are substances that reduce the number of roofs, and shingles. For example, the methods and composi microorganisms to a safe level. One official and legal defini 15 tions may be used to minimize fouling of marine markers. tion states that a sanitizer must be capable of killing 99.999%, Such markers constitute a large category of floating objects known as a 5 log reduction, of a specific bacterial test popu and are greatly impaired by the accumulation of marine lation, and to do so within 30 seconds. The main difference growth. Similarly, the methods and compositions may be between a sanitizer and a disinfectant is that at a specified use used on marine bulkheads. The accumulation of marine dilution, the disinfectant must have a higher kill capability for growth on bulkhead structures is detrimental to the bulkhead compared to that of a sanitizer. Very few structure over the long term. Furthermore, the growth causes disinfectants and sanitizers can sterilize (the complete elimi significant short term effects that are aesthetically displeasing nation of all microorganisms), and those that can depend and dangerous. Moreover, the harsh abrasive characteristics entirely on their mode of application. Bacterial of the hard growth can result in major damage to vessels. are most resistant to disinfectants, however Some viruses and 25 Similarly, the present invention can be used to minimize bacteria also possess some tolerance. The present invention blockages due to fouling by marine growth of heat exchang relates in one embodiment to use of the antimicrobial com ers, evaporators, condensers and fire and flushing systems, position as a sanitizer and/or a disinfectant. thus resulting in significant decreases in maintenance costs Preservative for all categories of marine structures. The invention also relates to the use of the antimicrobial 30 The antimicrobial composition can in one embodiment be composition as a preservative, such as in nutritional and/or included in a paint Such as a paint for marine vessels. Paints pharmaceutical composition. A preservative is a natural or according to the invention include the antimicrobial compo synthetic chemical that is added to products such as foods, sition in an amount effective to reduce the growth of pharmaceuticals, paints, biological samples, wood, etc. to unwanted or undesirable microorganisms. Such composi prevent decomposition by microbial growth or by undesirable 35 tions and/or paints may be in a variety of forms, including chemical changes. paints, lacquers, pastes, laminates, epoxies, resins, waxes, An embodiment relates to the use of the antimicrobial gels, and glues in addition to otherforms known to one of skill composition as a preservative in a feed composition/food in the art. conservation. The antimicrobial composition according to the present Anti-Fouling 40 invention can be used for prevention and/or inhibition of any In one embodiment the antimicrobial composition is used type of fouling including the types mentioned above. for anti-fouling. Anti-fouling is the process of removing or The antimicrobial composition can also be used for con inhibiting the accumulation of biofouling. Biofouling or bio servation of e.g. food/feed, drinkS/beverages, pharmaceuti logical fouling is the undesirable accumulation of microor cals and cosmetics. ganisms, plants, algae, and animals on Surfaces such as Sub 45 Anti-Bacterial Effect merged structures like ships' hulls. In another preferred embodiment the antimicrobial com The antimicrobial composition can be used for controlling, position has an anti-bacterial effect. The antibacterial effect reducing and/or eliminating over time the number of unde can in one embodiment be employed in food production Such sirable microorganisms in a bio-film. as in the dairy industry. In another embodiment the antimi Biofouling is also found in membrane systems, such as 50 crobial composition can be used in hospitals such as in an membrane bioreactors and reverse osmosis spiral wound operating room. membranes. In the same manner it is found as fouling in In one embodiment the antimicrobial composition accord cooling water cycles of large industrial equipments and ing to the present invention is a C. finnarchicus homogenate power stations. Biofouling is divided into microfouling— for use as a medicament. biofilm formation and bacterial adhesion—and macrofoul 55 In one embodiment the antimicrobial composition accord ing—attachment of larger organisms, of which the main cul ing to the present invention can be used for inhibition and/or prits are barnacles, mussels, polychaete worms, bryozoans, prevention of growth of or more bacteria Such as one or more and seaweed. Together, these organisms form a fouling com bacteria selected from the group consisting of Acetobacter munity. aurantius, Acinetobacter species: , Biofouling can occur on any Surface Submerged in water 60 Acinetobacter calcoaceticus, Acinetobacter johnsonii, Such as for example on ships. Other examples of surfaces that Acinetobacter junii, Acinetobacter lwofii, Acinetobacter can be exposed to biofouling are any installations, mem radioresistens, Acinetobacter septicus, Acinetobacter schin branes, nets, measuring equipment or other equipment in dleri, Acinetobacter ursingii; Actinomyces species: Actino aquaculture. myces bovis, Actinomyces bowdenii, Actinomyces canis, Acti Biofouling can also occur in groundwater wells where 65 nomyces cardiffensis, Actinomyces catuli, Actinomyces buildup can limit recovery flow rates, and in the exterior and coleocanis, Actinomyces dentalis, Actinomyces denticolens, interior of ocean-laying pipes. In the latter case it has been Actinomyces europaeus, Actinomyces funkei, Actinomyces US 8,647,676 B2 17 18 georgiae, Actinomyces gerencseriae, Actinomyces grae (), Bordetella petri, Bordetella trematum, venitzii, Actinomyces hongkongensis, Actinomyces hordeo Borrelia species: Borrelia burgdorferi, Borrelia afzelii, Bor vulneris, Actinomyces howellii, Actinomyces humiferus, Acti relia anserina, Borrelia garinii, Borrelia valaisiana, Borrelia nomyces hyovaginalis, Actinomyces israelii, Actinomyces hermsii, Borrelia Parkeri, Borrelia recurrentis, Bosea spe marinammalium, Actinomyces meyeri, Actinomyces cies, Bradyrhizobium species, Brenneria species, naeslundii, Actinomyces nasicola, Actinomyces neuii, Acti species: , Brucella Canis, Brucella meliten nomyces Odontolyticus, Actinomyces Oricola, Actinomyces sis, Brucella neotomae, Brucella ovis, Brucella suis, Brucella radicidentis, Actinomyces radingae, Actinomyces slackii, pinnipediae, Buchnera species, Budvicia species, Burkhold Actinomyces Streptomycini, Actinomyces suinastitidis, Acti eria species: Burkholderia cepacia (Pseudomonas cepacia), nomyces suis, Actinomyces turicensis, Actinomyces urogeni 10 (Pseudomonas mallei/ talis, Actinomyces vaccinaxillae, Actinomyces viscosus, mallei), Burkholderia pseudomallei (Pseudomonas Actinobacillus species: Actinobacillus actinomycetemcomi pseudomalilei); Buttiauxella species, Calymmatobacterium tans, Actinobacillus arthritidis, Actinobacillus capsulatus, granulomatis, Campylobacter species: Campylobacter coli, Actinobacillus delphinicola, Actinobacillus equuli, Actino Campylobacter concisus, Campylobacter curvus, Campylo hominis, Actinobacillus indolicus, Actinobacillus 15 bacter fetus, Campylobacter gracilis, Campylobacter hel lignieresi, Actinobacillus minor; Actinobacillus muris, Acti veticus, Campylobacter hominis, Campylobacter hyointesti nobacillus pleuropneumoniae, Actinobacillus porcinus, Acti nalis, Campylobacter insulaenigrae, , nobacillus rossii, Actinobacillus Scotiae, Actinobacillus Campylobacter lanienae, Campylobacter lari, Campylo seminis, Actinobacillus succinogenes, Actinobacillus suis, bacter mucosalis, Campylobacter rectus, Campylobacter Actinobacillus ureae, Aeromonas species: Aeromonas Showae, Campylobactersputorum, Campylobacter upsalien allosaccharophila, Aeromonas bestiarum, Aeromonas sis, Capnocytophaga canimorsus (Dysgonic fermenter type bivalvium, Aeromonas encheleia, Aeromonas enteropelo 2), Corynebacterium species, , genes, Aeromonas euchrenophila, , Cedecea species, species: Chlamydia trachoma Aeromonas ichthiosmia, Aeromonas jandaei, Aeromonas tis (), Chlamydia muridarum, media, Aeromonas molluscorum, Aeromonas popoffii, Aero 25 Chlamydia suis, Chlamydophila species: Chlamydophila monas punctata, Aeromonas Salmonicida, Aeromonas Schu pneumoniae, Chlamydophila psittaci (Psittacosis), Chlamy bertii, Aeromonas Sharmana, Aeromonas simiae, Aeromonas dophila pecorum, Chlamydophila abortus, Chlamydophila sobria, , Afipia felis, Agrobacterium spe felis, Chlamydophila caviae, Citrobacter species: Citro cies: Agrobacterium radiobacter, Agrobacterium rhizogenes, bacter amalonaticus, Citrobacter braakii, Citrobacter farm Agrobacterium rubi, Agrobacterium tumefaciens, Agrono 30 eri, , Citrobacter gillenii, Citrobacter nas species, Alcaligenes species: Alcaligenes aquatilis, intermedius, aka Citrobacter diversus, Alcaligenes eutrophus, Alcaligenes faecalis, Alcaligenes Citrobacter murliniae, Citrobacter rodentium, Citrobacter latus, Alcaligenes xylosoxidans, Alishewanella species, Sedlaki, Citrobacter werkmanii, Citrobacter youngae, Alterococcus species, Anaplasma phagocytophilum, Ana Clostridium species: Clostridium botulinum, Clostridium dif plasma marginale, Aquamonas species, Arcanobacterium 35 ficile, Clostridium novyi, Clostridium septicum, Clostridium haemolyticum, Aranicola species, Arsenophonus species, tetani (Tetanus), Clostridium welchii (Clostridium perfirin Azotivirga species, Azotobacter vinelandii, Azotobacter gens); Corynebacterium species: Corynebacterium diphthe chroococcum, Bacillary (), Bacillus riae (Diphtheria), Corynebacterium amycolatum, Coryne species: Bacillus abortus (Brucella melitensis biovar abor bacterium aquaticum, Corynebacterium bovis, tus), Bacillus anthracis (Anthrax), Bacillus brevis, Bacillus 40 Corynebacterium equi, Corynebacterium flavescens, cereus, Bacillus coagulans, Bacillus fusiformis, Bacillus glo Corynebacterium glutamicum, Corynebacterium haemolyti bigii, Bacillus licheniformis, Bacillus megaterium, Bacillus cum, Corynebacterium jeikeiun (corynebacteria of group mycoides, Bacillus natto, Bacillus Stearothermophilus, JK), Corynebacterium minutissimum (Erythrasma), Coryne Bacillus subtilis, Bacillus sphaericus, Bacillus thuringiensis, bacterium parvum (also called Propionibacterium acnes), Bacteroides species: Bacteroides forsythus (Tannerella for 45 Corynebacterium pseudodiptheriticum (also called Coryne sythensis), Bacteroides acidifaciens, Bacteroides distasonis bacterium hofinannii), Corynebacterium pseudotuberculosis (reclassified as Parabacteroides distasonis), Bacteroides gin (also called Corynebacterium Ovis), Corynebacterium pyo givalis, Bacteroides gracilis, Bacteroides fragilis, Bacteroi genes, Corynebacterium urealyticum (corynebacteria of des Oris, Bacteroides ovatus, Bacteroides putredinis, group D2), Corynebacterium renale, Corynebacterium stria Bacteroides pyogenes, Bacteroides Stercoris, Bacteroides 50 tum, Corynebacterium tenuis (Trichomycosis palmellina, Tri suis, Bacteroides tectus, Bacteroides thetaiotaomicron, chomycosis axillaris), Corynebacterium ulcerans, Coryne Bacteroides vulgatus, species: Bartonella bacterium xerosis, (Q ), Cronobacter alsatica, , Bartonella birtlesii, Bar species: Cronobacter Sakazakii, Cronobacter malonaticus, tonella bovis, Bartonella capreoli, Bartonella clarridgeiae, Cronobacter turicensis, Cronobacter muytjensii, Crono , , Bartonella gra 55 bacter dublimensis, Delftia acidovorans (Comamonas aci hamii, (cat scratch fever), Bartonella dovorans), Dickeya species, Edwardsiella species, Eikenella koehlerae, Bartonella muris, , Bar corrodens, Enterobacter species: Enterobacter aerogenes, tonella quintana, Bartonella rochalinae, Bartonella Schoen– , Enterobacter Sakazaki Enterococcus buchii, , Bartonella taylorii, Bartonella tri species: Enterococcus avium, Enterococcus durans, Entero bocorum, Bartonella vinsonii spp. Arupensis, Bartonella 60 coccus faecalis (Streptococcus faecalis/Streptococcus Group vinsonii spp. Berkhofii, Bartonella vinsonii spp. Vinsonii, D), Enterococcus faecium, Enterococcus solitarius, Entero Bartonella washoensis; BCG (Bacille Calmette-Guerin), coccus gallinarum, Enterococcus maloratus, Ehrlichia Bergeyella zoohelicum (Weeksella zoo helcum), Bifidobacte chafeensis, Erysipelothrix rhusiopathiae, Erwinia species, rium bifidum, Blastobacter species, Blochmannia species, Escherichia species: Escherichia adecarboxylata, Escheri Bordetella species: , , 65 chia albertii, Escherichia blattae, , Escheri Bordetella bronchiseptica, , Bordetella chia fergusonii, Escherichia hermannii, Escherichia vuln holmesii, , eris, Ewingella species, Flavobacterium species: US 8,647,676 B2 19 20 Flavobacterium aquatile, Flavobacterium branchiophilum, gasseri, Lactobacillus gastricus, Lactobacillus ghanensis, Flavobacterium columnare, Flavobacterium flevense, Fla Lactobacillus graminis, Lactobacillus hammesii, Lactobacil vobacterium gondwanense, Flavobacterium hydatis, Fla lus hamsteri, Lactobacillus harbinensis, Lactobacillus haya vobacterium johnsoniae, Flavobacterium pectinovorum, kitensis, Lactobacillus helveticus, Lactobacillus hilgardii, Flavobacterium psychrophilum, Flavobacterium saccharo 5 Lactobacillus homohiochii, Lactobacillus iners, Lactobacil philum, Flavobacterium salegens, Flavobacterium scoph lus inglu viei, Lactobacillus intestinalis, Lactobacillus jens thalmum, Flavobacterium succinans, enii, Lactobacillus johnsonii, Lactobacillus kalixensis, Lac (Tularaemia), Francisella novicida, Francisella philomira tobacillus kefiranofaciens, Lactobacillus Refiri, gia, Fusobacterium species: Fusobacterium necrophorum Lactobacillus kimchii, Lactobacillus kitasatonis, Lactobacil (Lemierre Syndrome/Sphaerophorus necrophorus), Fuso 10 lus kunkeei, Lactobacillus leichmannii, Lactobacillus lind bacterium nucleatum, Fusobacterium polymorphum, Fuso neri, Lactobacillus malefermentans, Lactobacillus mali, Lac bacterium novum, Fusobacterium mortiferum, Fusobacte tobacillus manihotivorans, Lactobacillus mindensis, rium varium, Gardnerella vaginalis, Gemella haemolysans, Lactobacillus mucosae, Lactobacillus murinus, Lactobacil Gemella morbillorum (Streptococcus morbillorum), Gri lus nagelii, Lactobacillus namurensis, Lactobacillus manten montella species, species: Haemophilus aegyp 15 sis, Lactobacillus Oligofermentans, Lactobacillus Oris, Lac tius (Koch-Weeks bacillus), Haemophilus aphrophilus, Hae tobacillus panis, Lactobacillus pantheris, Lactobacillus mophilus avium, (), parabrevis, Lactobacillus parabuchneri, Lactobacillus para Haemophilus felis, Haemophilus haemolyticus, Haemophi collinoides, Lactobacillus parafarraginis, Lactobacillus par lus influenzae (Pfeiffer bacillus), Haemophilus paracunicu akefiri, Lactobacillus parallimentarius, Lactobacillus para lus, Haemophilus parahaemolyticus, Haemophilus parain plantarum, Lactobacillus pentosus, Lactobacillus perolens, fluenzae, Haemophilus paraphrophilus (Aggregatibacter Lactobacillus plantarum, Lactobacillus pontis, Lactobacil aphrophilus), Haemophilus pertussis, Haemophilus pittma lus psittaci, Lactobacillus rennini, Lactobacillus reuteri, niae, Haemophilus Somnus, Haemophilus vaginalis, Hafinia Lactobacillus rhamnosus, Lactobacillus rimae, Lactobacil species, Hafnia alvei, species: Helicobacter lus rogosae, Lactobacillus rossiae, Lactobacillus ruminis, acinonychis, Helicobacter anseris, Helicobacter aurati, 25 Lactobacillus Saerimneri, Lactobacillus sakei, Lactobacillus , Helicobacter bizzozeronii, Helicobacter salivarius, Lactobacillus Sanfranciscensis, Lactobacillus brantae, , , Heli satsumensis, Lactobacillus secaliphilus, Lactobacillus cobacter cholecystus, , Helicobacter sharpeae, Lactobacillus Siliginis, Lactobacillus spicheri, cynogastricus, , Helicobacter fennelliae, Lactobacillus Suebicus, Lactobacillus thailandensis, Lacto Helicobacterganmani, Helicobacter heilmannii (Gastrospir 30 bacillus ultunensis, Lactobacillus vaccinostercus, Lactoba illum hominis), , Helicobacter cillus vaginalis, Lactobacillus versmoldensis, Lactobacillus mesocricetorum, Helicobacter marmotae, Helicobacter vini, Lactobacillus vitulinus, Lactobacillus zeae, Lactobacil muridarum, Helicobacter mustelae, Helicobacter pameten lus zymae, Leclercia species, species: Legionella sis, , (stomach adelaidensis, , , ulcer), Helicobacter rappini, , Heli 35 Legionella birminghamensis, Legionella bOzemanii, cobacter Salomonis, , Helicobacter , , Legionella typhlonius, Helicobacter winghamensis; Human granulo cherrii, Legionella cincinnatiensis, , cytic (Anaplasma phagocytophilum/Ehrlichia Legionella drancourti, Legionella drozanski, Legionella phagocytophila), Human monocytotropic ehrlichiosis erythra, Legionella fairfieldensis, , (Monocytic ehrlichiosis/Ehrlichia chafeensis), 40 Legionella feelei, , Legionella genomo species: (Calymmatobacterium species, , , granulomatis), Klebsiella mobilis, Klebsiella Ornithinolytica, , , Legionella , Klebsiella ozaenae, Klebsiella planti israelensis, Legionella jamestowniensis, 'Candidatus cola, , Klebsiella rhinoscleromatis, Legionella jeonii, , Legionella lansin Klebsiella Singaporensis, Klebsiella terrigena, Klebsiella 45 gensis, , , trevisani, Klebsiella varicola, , Kluyvera , , Legionella species, Lactobacillus species: Lactobacillus acetotolerans, micdadei, , , Lactobacillus acidifarinae, Lactobacillus acidipiscis, Lacto , , Legionella bacillus acidophilus (Doderlein bacillus), Lactobacillus agi pneumophila, , Legionella quinliva lis, Lactobacillus algidus, Lactobacillus alimentarius, Lac 50 nii, , , tobacillus amylolyticus, Lactobacillus amylophilus, , , Legionella Lactobacillus amylotrophicus, Lactobacillus amylovorus, Shakespearei, , Legionella Steiger Lactobacillus animalis, Lactobacillus antri, Lactobacillus waltii, , , apodemi, Lactobacillus aviarius, Lactobacillus bifermen , , Legionella tans, Lactobacillus brevis, Lactobacillus buchneri, Lactoba 55 worsleiensis, , Leminorella species, cillus camelliae, Lactobacillus casei, Lactobacillus cat Leptospira species: Leptospira interrogans, Leptospira kir enaformis, Lactobacillus ceti, Lactobacillus coleohominis, Schneri, Leptospira noguchii, Leptospira alexanderi, Lep Lactobacillus collinoides, Lactobacillus composti, Lactoba to spira weilii, Leptospira genomospecies 1, Leptospira borg cillus concavus, Lactobacillus coryniformis, Lactobacillus petersenii, Leptospira Santarosai, Leptospira inadai, crispatus, Lactobacillus crustorum, Lactobacillus curvatus, 60 Leptospira fainei, Leptospira broomii, Leptospira licerasiae, Lactobacillus delbrueckii, Lactobacillus delbrueckii subsp. Leptospira biflexia, Leptospira meyeri, Leptospira wolbachii, Bulgaricus, Lactobacillus delbrueckii Subsp. Lactis, Lacto Leptospira genomospecies 3, Leptospira genomospecies 4, bacillus diolivorans, Lactobacillus equi, Lactobacillus Leptospira genomospecies 5; Lepromatous leprosy (Daniels equigenerosi, Lactobacillus farraginis, Lactobacillus far sen-Boeck disease), Leptospira canicola, Leptospira hebdo ciminis, Lactobacillus fermentum, Lactobacillus formicalis, 65 madis, Leptospirosis (Weil disease/Leptospira icterohaemor Lactobacillus fructivorans, Lactobacillus frumenti, Lactoba rhagiae/Leptospira interrogans SOWa. cillus fitchuensis, Lactobacillus gallinarum, Lactobacillus icterohaemorrhagiae), Leptotrichia, Leuconostoc species: US 8,647,676 B2 21 22 Leuconostoc carnosum, Leuconostoc citreum, Leuconostoc Mycobacterium neoaurum, Mycobacterium newOrleansense, durionis, Leuconostoc fallax, Leuconostocficulneum, Leu Mycobacterium nonchromogenicum, Mycobacterium novo conostoc fructosum, Leuconostoc garlicum, Leuconostoc castrense, Mycobacterium obuense, Mycobacterium palus gasicomitatum, Leuconostoc gelidum, Leuconostoc inhae, tre, Mycobacterium parafortuitum, Mycobacterium paras Leuconostoc kimchii, Leuconostoc lactis, Leuconostoc 5 crofulaceum, Mycobacterium parmense, Mycobacterium mesenteroides, Leuconostoc pseudoficulneum, Leuconostoc peregrinum, Mycobacterium phlei, Mycobacterium phocai pseudomesenteroides, Listeria species: Listeria grayi, List cum, Mycobacterium pinnipedii, Mycobacterium porcinum, eria innocua, Listeria ivanovii, Listeria monocytogenes Mycobacterium poriferae, Mycobacterium pseudoshottsii, (Listeriosis), Listeria Seeligeri, Listeria wellshimeri; Metha Mycobacterium pulveris, Mycobacterium psychrotolerans, nobacterium extroquens, Microbacterium multiforme, 10 Mycobacterium pyrenivorans, Mycobacterium rhodesiae, Micrococcus species: Micrococcus antarcticus, Micrococcus Mycobacterium Saskatchewanense, Mycobacterium scrofit flavus, Micrococcus luteus, Micrococcus lylae, Micrococcus laceum, Mycobacterium Senegalense, Mycobacterium Seou mucilaginosis, Micrococcus roseus, Micrococcus seden lense, Mycobacterium septicum, Mycobacterium Shimoidei, tarius, Mobiluncus, Moellerella species, Morganella species, Mycobacterium shottsii, Mycobacterium simiae, Mycobacte Moraxella species: Moraxella atlantae, Moraxella boevrei, 15 rium Smegmatis, Mycobacterium sphagni, Mycobacterium , Moraxella canis, Moraxella caprae, Szulgai, Mycobacterium terrae, Mycobacterium thermore (Branhamella catarrhalis), Moraxella sistibile, Mycobacterium tokaiense, Mycobacterium triplex, caviae, Moraxella cuniculi, Moraxella equi, Moraxella lacu Mycobacterium triviale, Mycobacterium tuberculosis (major nata, Moraxella lincolnii, Moraxella nonliquefaciens, cause of human tuberculosis), Mycobacterium bovis, Myco Moraxella Oblonga, Moraxella Osloensis, Moraxella saccha bacterium africanum, Mycobacterium canetti, Mycobacte rolytica, Morganella morganii, Mycobacterium species: rium caprae, Mycobacterium pinnipedii, Mycobacterium Mycobacterium abscessus, Mycobacterium africanum, tusciae, Mycobacterium ulcerans (causes Bairnsdale ulcer/ Mycobacterium agri, Mycobacterium aichiense, Mycobacte Buruli ulcer), Mycobacterium vaccae, Mycobacterium van rium alvei, Mycobacterium arupense, Mycobacterium asiati baalenii, Mycobacterium wolinskyi, Mycobacterium xenopi; cum, Mycobacterium aubagnense, Mycobacterium aurum, 25 Mycoplasma species: Mycoplasma fermentans, Mycoplasma Mycobacterium austroafricanum, Mycobacterium avium genitalium, , Mycoplasma penetrans, (Battey disease/Lady Windermere syndrome), Mycobacte Mycoplasma phocacerebrale, Mycoplasma pneumoniae, rium avium paratuberculosis (implicated in Crohn's disease Nanukayami (Seven-day fever/Gikiyami), Neisseria species: in humans and Johne's disease in sheep), Mycobacterium Neisseria gonorrhoea (Gonococcus/), Neisseria avium Silvaticum, Mycobacterium avium "hominissuis', 30 meningiditis (Meningococcus), Neisseria sicca, Neisseria Mycobacterium colombiense, Mycobacterium boenickei, cinerea, Neisseria elongata, Neisseria flavescens, Neisseria Mycobacterium bohemicum, Mycobacterium boiletii, Myco lactanica, Neisseria mucosa, Neisseria polysaccharea, Neis bacterium botniense, Mycobacterium bovis (Bovine tubercu seria subflava, Nitrobacter species, Nocardia species: losis), Mycobacterium branderi, Mycobacterium brisban Nocardia asteroides, Nocardia brasiliensis, Nocardia ense, Mycobacterium brumae, Mycobacterium canariasense, 35 caviae; Noma (cancrum oriS/gangrenous stomatitis), Obe Mycobacterium caprae, Mycobacterium cellatum, Mycobac sumbacterium, Oligotropha species, terium chelonae, Mycobacterium chimaera, Mycobacterium (Scrub ), Oxalobacter formigenes, Pantoea species: chitae, Mycobacterium chlorophenolicum, Mycobacterium Pantoea agglomerans, Pantoea ananatis, Pantoea citrea, chubuense, Mycobacterium conceptionense, Mycobacterium Pantoea dispersa, Pantoea punctata, Pantoea Stewartii, Pan confluentis, Mycobacterium conspicuum, Mycobacterium 40 toea terrea, species: Pasteurella aerogenes, Pas cookii, Mycobacterium cosmeticum, Mycobacterium diern teurella anatis, Pasteurella avium, Pasteurella bettvae, Pas hoferi, Mycobacterium doricum, Mycobacterium du valii, teurella caballi, , , Mycobacterium elephantis, Mycobacterium fallax, Myco Pasteurella gallicida, Pasteurella gallinarum, Pasteurella bacterium farcinogenes, Mycobacterium flavescens, Myco granulomatis, Pasteurella langaaensis, Pasteurella lymphan bacterium florentinum, Mycobacterium fluoroanthenivorans, 45 gitidis, Pasteurella mairii, , Pasteurella Mycobacterium fortuitum, Mycobacterium fortuitum Subsp. pneumotropica, Pasteurella Skyensis, , Acetamidolyticum, Mycobacterium federiksbergense, Pasteurella testudinis, Pasteurella trehalosi, Pasteurella tulla Mycobacterium gadium, Mycobacterium gastri, Mycobacte rensis, Pasteurella ureae, Pasteurella volantium, Pediococ rium genavense, Mycobacterium gilvium, Mycobacterium cus species: Pediococcus acidilactici, Pediococcus cellicola, goodi, Mycobacterium gordonae (Mycobacterium aquae), 50 Pediococcus claussenii, Pediococcus damnosus, Pediococ Mycobacterium haemophilum, Mycobacterium hassiacum, cus dextrinicus, Pediococcus ethanolidurans, Pediococcus Mycobacterium heckeshornense, Mycobacterium heidelber inopiniatus, Pediococcus parvulus, Pediococcuspentosaceus, gense, Mycobacterium hiberniae, Mycobacterium hodleri, Pediococcus stilesii Peptostreptococcus species: Peptostrep Mycobacterium holsaticum, Mycobacterium houstonense, tococcus anaerobius, Peptostreptococcus asaccharolyticus, Mycobacterium immunogenium, Mycobacterium interjectum, 55 Peptostreptococcus harei, Peptostreptococcus hydrogenalis, Mycobacterium intermedium, Mycobacterium intracellulare, Peptostreptococcus indoliticus, Peptostreptococcus ivorii, Mycobacterium kansasii, Mycobacterium komossense, Peptostreptococcus lacrimalis, Peptostreptococcus lactolyti Mycobacterium kubicae, Mycobacterium kumamotonense, cus, Peptostreptococcus magnus, Peptostreptococcus micros, Mycobacterium lacus, Mycobacterium lentiflavum, Myco Peptostreptococcus Octavius, Peptostreptococcus previotii, bacterium leprae (causes leprosy or Hansen disease/Hans 60 Peptostreptococcus tetradius, Peptostreptococcus vaginalis, eniasis), Mycobacterium lepraemurium, Mycobacterium Photorhabdus species, Photorhizobium species, Plesiomo madagascariense, Mycobacterium mageritense, Mycobacte nas Shigelloides, Porphyromonas gingivalis, Pragia species, rium malmoense, Mycobacterium marinum (Fish tank granu Prevotella, Propionibacterium species: Propionibacterium loma), Mycobacterium massiliense, Mycobacterium microti, acnes, Propionibacterium propionicus, Proteus species: Pro Mycobacterium monacense, Mycobacterium montefiorense, 65 teus mirabilis, Proteus morganii, Proteus penneri, Proteus Mycobacterium moriokaense, Mycobacterium mucogeni rettgeri, , Providencia species: Providencia cum, Mycobacterium murale, Mycobacterium nebraskense, friedericiana, , Pseudomonas species: US 8,647,676 B2 23 24 , Pseudomonas alcaligenes, ettsia Conorii, , , Rickettsia Pseudomonas anguilliseptica, Pseudomonas argentinensis, mooseri, (Typhus fever), Rickettsia Pseudomonas borbori, Pseudomonas citronellolis, rickettsii, Rickettsia Siberica, , Rickettsia Pseudomonas flavescens, Pseudomonas mendocina, Conorii, , Rickettsia psittaci, Rickettsia Pseudomonas nitroreducens, Pseudomonas Oleovorans, quintana, , Rickettsia trachomae, Rothia Pseudomonas pseudoalcaligenes, Pseudomonas resino dentocariosa, Salmonella species: Salmonella arizonae, Sal vorans, Pseudomonas Straminea, Pseudomonas aurantiaca, monella Bongori, , Salmonella enteridi Pseudomonas aureofaciens, Pseudomonas chlororaphis, tis, Salmonella paratyphi, Salmonella typhi (), Pseudomonas fragi, Pseudomonas lundensis, Pseudomonas Salmonella typhimurium, Salmonella Salamae, Salmonella taetrolens, Pseudomonas Antarctica, Pseudomonas azotofor 10 arizonae, Salmonella diarizonae, Salmonella houtenae, Sal mans, Pseudomonas brassicacearum, Pseudomonas bren monella indica, species, Serratia species: Serratia neri, Pseudomonas Cedrina, Pseudomonas corrugate, entomophila, Serratia ficaria, Serratia fonticola, Serratia Pseudomonas fluorescens, Pseudomonas gessardii, grimesii, Serratia liquefaciens, , Serra Pseudomonas libanensis, Pseudomonas mandelii, tia Odoriferae, Serratia plvmuthica, Serratia proteamacu Pseudomonas marginalis, Pseudomonas mediterranea, 15 lans, Serratia quinivorans, Serratia rubidaea, Serratia ure Pseudomonas meridiana, Pseudomonas migulae, ilytica, Shewanella putrefaciens, , Shigella Pseudomonas mucidolens, Pseudomonas Orientalis, dysenteriae, , , Sodalis spe Pseudomonas panacis, Pseudomonas proteolytica, cies, Spirillum species: Spirillum minus rat bite fever, Staphy Pseudomonas rhodesiae, Pseudomonas synxantha, lococcus species: Staphylococcus aureus, Staphylococcus Pseudomonas thivervalensis, Pseudomonas tolaasii, auricularis, Staphylococcus capitis, Staphylococcus Caprae, Pseudomonas veronii, Pseudomonas denitrificans, Staphylococcus cohnii, Staphylococcus epidermidis, Staphy Pseudomonas pertucinogena, Pseudomonas Cremoricolo lococcus felis, Staphylococcus haemolyticus, Staphylococcus rata, Pseudomonas fulva, Pseudomonas monteilii, hominis, Staphylococcus intermedius, Staphylococcus lug Pseudomonas mosselii, Pseudomonas Oryzihabitans, dunensis, Staphylococcus pettenkoferi, Staphylococcus Pseudomonas parafiulva, Pseudomonas plecoglossicida, 25 Saprophyticus, Staphylococcus Schleiferi, Staphylococcus Pseudomonas putida, Pseudomonas balearica, Pseudomo simulans, Staphylococcus vitulus, Staphylococcus warneri, nas luteola, Pseudomonas Stutzeri, Pseudomonas amygdale, Staphylococcus xylosus, Stenotrophomonas species: Pseudomonas avellanae, Pseudomonas Caricapapayae, Stenotrophomonas acidaminiphila, Stenotrophomonas dok Pseudomonas cichorii, Pseudomonas coronafaciens, donensis, Stenotrophomonas koreensis, Stenotrophomonas Pseudomonas ficuserectae, Pseudomonas meliae, 30 maltophilia, Stenotrophomonas nitritireducens, Stenotroph Pseudomonas Savastanoi, Pseudomonas syringae, Omonas rhizophila, Streptobacillus species: Streptobacillus Pseudomonas viridiflava, Pseudomonas abietaniphila, moniliformis (Streptobacillary rat bite fever); Streptococcus Pseudomonas acidophila, Pseudomonas agarici, Pseudomo species: Streptococcus Group A, Streptococcus Group B, nas alcaliphila, Pseudomonas alkanolytica, Pseudomonas Streptococcus agalactiae, Streptococcus aginosus, Strepto amyloderamosa, Pseudomonas asplenii, Pseudomonas azo 35 coccus avium, Streptococcus bovis, Streptococcus canis, tifigens, Pseudomonas cannabina, Pseudomonas coenobios, Streptococcus Cricetus, Streptococcus faceium, Streptococ Pseudomonas congelans, Pseudomonas costantinii, cus faecalis, Streptococcus ferus, Streptococcus gallinarum, Pseudomonas cruciviae, Pseudomonas delhiensis, Streptococcus lactis, Streptococcus milleri, Streptococcus Pseudomonas excibis, Pseudomonas extremorientalis, mition; Streptococcus mitis, Streptococcus mutans, Strepto Pseudomonas federiksbergensis, Pseudomonas fuscovagi 40 coccus oralis, Streptococcus peroris, Streptococcus pneumo nae, Pseudomonas gelidicola, Pseudomonas grimontii, niae, Streptococcus pyogenes, Streptococcus ratti, Strepto Pseudomonas indica, Pseudomonas jessenii, Pseudomonas coccus salivarius, Streptococcus sanguinis, Streptococcus injuensis, Pseudomonas kilomensis, Pseudomonas knack sobrinus, Streptococcus parasanguinis, Streptococcus suis, mussii, Pseudomonas koreensis, Pseudomonas lini, Streptococcus thermophilus, Streptococcus vestibularis, Pseudomonas lutea, Pseudomonas moraviensis, Pseudomo 45 Streptococcus viridans, Streptococcus uberis, Streptococcus nas Otitidis, Pseudomonas pachastrellae, Pseudomonas pal ZOOepidemicus, Tatumella species, Trabulsiella species, Tre leroniana, Pseudomonas papaveris, Pseudomonas peli, ponema species: Treponema carateum (Pinta), Treponema Pseudomonas perolens, Pseudomonas poae, Pseudomonas denticola, Treponema endemicum (Beel), Treponema palli pohangensis, Pseudomonas psychrophila, Pseudomonas dum (), Treponema pertenue (Yaws); Tropheryma psychrotolerans, Pseudomonas rathonis, Pseudomonas rep 50 whipplei (Whipple disease), Tuberculoid leprosy, Urea tilivora, Pseudomonas resiniphila, Pseudomonas plasma urealyticum, Veillonella, Vibrio species: Vibrio aero rhizosphaerae, Pseudomonas rubescens, Pseudomonas genes, Vibrio aestuarianus, Vibrio agarivorans, Vibrio alben Salomonii, Pseudomonas segitis, Pseudomonas septica, sis, , Vibrio brasiliensis, Vibrio calviensis, Pseudomonas simiae, Pseudomonas suis, Pseudomonas ther Vibrio Campbellii, Vibrio chagasii, (), motolerans, Pseudomonas tremae, Pseudomonas trivialis, 55 Vibrio cincinnatiensis, Vibrio Comma, Vibrio coralliilyticus, Pseudomonas turbinellae, Pseudomonas tuticorinensis, Vibrio crassostreae, Vibrio cyclitrophicus, Vibrio diabolicus, Pseudomonas unsongensis, Pseudomonas vancouverensis, Vibrio diazotrophicus, Vibrio ezurae, Vibrio fischeri, Vibrio Pseudomonas Vranovensis, Pseudomonas xanthomarina, fluvialis, Vibriofortis, Vibrio furnissii, Vibrio gallicus, Vibrio Rahnella species, Ralstonia species: Ralstonia basilensis, gazogenes, Vibrio gigantis, Vibrio hallioticoli, Vibrio harveyi, Ralstonia campinensis, Ralstonia eutropha, Ralstonia gilar 60 Vibrio hepatarius, Vibrio hispanicus, Vibrio ichthyoenteri, dii, Ralstonia insidiosa, Ralstonia mannitolilytica, Ralstonia Vibrio kanaloae, Vibrio lentus, Vibrio litoralis, Vibrio logei, metallidurans, Ralstonia paucula, Ralstonia pickettii, Ral Vibrio mediterranei, Vibrio metschnikovii, Vibrio mimicus, stonia respiraculi, Ralstonia Solanacearum, Ralstonia syzy Vibrio mytili, Vibrio matriegens, Vibrio navarrensis, Vibrio gii, Ralstonia taiwanensis, Raoultella species, Rhodoblastus neonatus, Vibrio neptunius, Vibrio nereis, Vibrio nigripul species, Rhodopseudomonas species, , Rhizo 65 chritudo, Vibrio ordalii, Vibrio Orientalis, Vibrio pacinii, bium radiobacter, Rhodococcus equi, Rickettsia species: , Vibrio pectenicida, Vibrio penaei Rickettsia africae, , , Rick cida, Vibrio pomeroyi, Vibrio ponticus, Vibrio proteolyticus, US 8,647,676 B2 25 26 Vibrio rotiferianus, Vibrio ruber, Vibrio rumoiensis, Vibrio low mottle virus, Common cold virus, Comovirus, Condylo salmonicida, Vibrio scophthalmi, Vibrio splendidus, Vibrio mata accuminata, congenital cytomegalovirus, contagious superstes, Vibrio tapetis, Vibrio tasmaniensis, Vibrio tubi eethyma virus, contagious pustular dermatitis virus, Coro ashii, , Vibrio wodanis, Vibrioxuii, Vogesella navirus, Corriparta virus, coryza virus, cowpea chlorotic indigofera, Wigglesworthia species, Wolbachia species, mottle virus, cowpea mosaic virus, cowpea virus, cowpox Xenorhabdus species, , , virus, coxsackie virus, CPV (cytoplasmic polyhedrosis Yersinia pseudotuberculosis, and Yokenella species. virus), cricket paralysis virus, Crimean-Congo hemorrhagic Antiviral Effects fever virus, croup associated virus, Crypotovirus, Cucumovi In one embodiment the antimicrobial composition accord rus, Cypovirus, Cytomegalovirus (HCMV or Human Herp ing to the present invention can be used for inhibition and/or 10 esvirus 5 HHV-5), cytoplasmic polyhedrosis virus, Cytorhab prevention of growth of or more vira Such as one or more vira dovirus, deer papillomavirus, Deltaretrovirus (Human selected from the group consisting of Abelson murine leuke T-lymphotropic virus), Deformed wing virus DWV. Dengue, mia virus (Ab-MLV, A-MuDV), acute laryngotracheobron Densovirus, Dependovirus, Dhori virus, Dianthovirus, dip chitis virus (or HPIV), Adelaide River virus, Adeno-associ lorna virus, DNA virus, Dobrava-Belgrade Virus, Dog Flu, ated virus group (Dependevirus), Adenovirus, African horse 15 Drosophila C virus, duck B virus, duck hepatitis sickness virus, African swine fever virus, AIDS virus, Aleu virus 1, duck hepatitis virus 2, duovirus, Duvenhage virus, tian mink disease, parvovirus, alfalfa mosaic virus, Alphaher eastern equine encephalitis virus, eastern equine encephalo pesvirinae (including HSV 1 and 2 and varicella), Alpharet myelitis virus, Ebola virus, Ebola-like virus, Echovirus, rovirus (Avian leukosis virus, Rous sarcoma virus), echovirus 10, echovirus 28, echovirus 9, ectromelia virus, Alphavirus, alkhurma virus, ALV related virus, Amapari EEE virus (Eastern equine encephalitis virus), EIA virus virus, Andean potato mottle virus, Aphthovirus, Aquareovi (equine infectious anemia), EMC virus (Encephalomyocardi rus, arbovirus, arbovirus C. arbovirus group A, arbovirus tis), Emiliania huxleyi virus 86, encephalitis virus, encepha group B, Arenavirus group, Argentine hemorrhagic fever lomyocarditis virus, Endogenous retrovirus, Enterovirus, virus, Argentinian hemorrhagic fever virus, Arterivirus, Entomopoxyirinae, Entomopoxvirus A, Entomopoxvirus B, Astrovirus, Ateline herpesvirus group, Aujezky's disease 25 Entomopoxvirus C, enzyme elevating virus, epidemic hem virus, Aura virus, Ausduk disease virus, Australian bat lys orrhagic fever virus, epizootic hemorrhagic disease virus, savirus, Aviadenovirus, avian erythroblastosis virus, avian Epsilonretrovirus, Epstein-Barr virus (EBV: Human herpes infectious bronchitis virus, avian leukemia virus, Avian leu virus 4 HHV-4), equid alphaherpesvirus 1, equid alphaherp kosis virus (ALV), avian lymphomatosis virus, avian myelo esvirus 4, equid herpesvirus 2, equine abortion virus, equine blastosis virus, avian paramyxovirus, avian pneumoencepha 30 arteritis virus, equine encephalosis virus, equine infectious litis virus, avian reticuloendotheliosis virus, avian sarcoma anemia virus, equine morbillivirus, equine rhinopneumonitis virus, avian type C retrovirus group, Avihepadnavirus, Avi virus, equine rhinovirus, Eubenangu virus, European elk pap poxvirus, B virus (Cercopithecine herpesvirus 1), B19 virus illomavirus, European Swine fever virus, Everglades virus, (Parvovirus B19), Babanki virus, baboon herpesvirus, bacte Eyach virus, Fabavirus, felid herpesvirus 1, feline calicivirus, rial virus, baculovirus, barley yellow dwarf virus, Barmah 35 feline fibrosarcoma virus, feline herpesvirus, feline immuno Forest virus, bean pod mottle virus, bean rugose mosaic virus, deficiency virus, feline infectious peritonitis virus, feline leu Bebaru virus, Berrimah virus, Betaherpesvirinae, betaretro kemia/sarcoma virus, feline leukemia virus, feline panleuko virus, Bird flu, Birnavirus, Bittner virus, BK virus, Black penia virus, feline parvovirus, feline sarcoma virus, feline Creek Canal virus, bluetongue virus, Bolivian hemorrhagic syncytial virus, Fijivirus, Filovirus, Flanders virus, Flavivi fever virus, Bomadisease virus, border disease of sheep virus, 40 rus, foot and mouth disease virus, Fort Morgan virus, Four borna virus, bovine alphaherpesvirus 1, bovine alphaherpes Cornershantavirus, fowladenovirus 1, Fowlpox virus, Friend virus 2, bovine coronavirus, bovine ephemeral fever virus, virus, Furovirus, Gammaherpesvirinae, gammaretrovirus, bovine virus, bovine leukemia virus, GB virus C (GBV-C; formerly Hepatitis G virus), Geminivi bovine leukosis virus, bovine mammillitis virus, bovine pap rus, German measles virus, Getah virus, gibbon ape leukemia illomavirus, bovine papular stomatitis virus, bovine parvovi 45 virus, green monkey virus (mullburg), glandular fever virus, rus, bovine syncytial virus, bovine type Concovirus, bovine goatpox virus, golden shinner virus, Gonometa virus, goose viral diarrhea virus, bracovirus, broad bean mottle virus, parvovirus, granulosis virus, Gross virus, ground Squirrel broad bean stain virus, brome mosaic virus, Bromovirus, virus, group A arbovirus, Guanarito virus, guinea Buggy Creek virus, bullet shaped virus group, Bunyamwera pig cytomegalovirus, guinea pig type C virus, Hantavirus, virus, Bunyavirus, Burkitt's lymphoma virus, Bwamba 50 hard clam reovirus, hare fibroma virus, HCMV (human Fever, Bwattany hetero virus, CA virus (Croup-associated cytomegalovirus), helper virus, hemadsorption virus 2, virus/parainfluenza vius type 2), Calicivirus, California hemagglutinating virus of Japan, hemorrhagic fever virus, encephalitis virus, camelpox virus, canarypox virus, canid Hendra virus, Henipaviruses, Hepadnavirus, hepatitis A herpesvirus, canine coronavirus, canine distemper virus, virus, , hepatitis C virus, hepatitis D (delta) canine herpesvirus, canine minute virus, canine parvovirus, 55 virus, hepatitis E virus, hepatitis F virus, hepatitis G virus, Cano Delgadito virus, Capillovirus, caprine arthritis virus, hepatitis nonA nonB virus, hepatoencephalomyelitis reovirus caprine encephalitis virus, Caprine Herpes Virus, Capripox 3, Hepatovirus, heron hepatitis B virus, herpes B virus, Her virus, Cardiovirus, Carlavirus, Carmovirus, carrot mottle pes simplex virus, virus 1, , Cassia yellow blotch virus, Caulimovirus, Cauliflower virus 2, Herpesvirus, Herpes Zoster, Herpes virus 6. Herpes mosaic virus, caviid herpesvirus 1, Cercopithecine herpesvi 60 virus 7. Herpes virus 8, Herpesvirus ateles, Herpesvirus rus 1, Cercopithecine herpesvirus 2, cereal yellow dwarf hominis, Herpesvirus Saimiri, Herpesvirus Suis, Herpesvirus virus, Chandipura virus, Changuinola virus, channel catfish varicellae, Highlands J virus, Hirame rhabdovirus, HIV-1, virus, Charleville virus, chickenpox virus, Chikungunya hog cholera virus, Hordeivirus, Horse Flu, HTLV-1, HTLV-2, virus, chimpanzee herpesvirus, Chordopoxyirinae, chub human adenovirus 2, human alphaherpesvirus 1, human reovirus, chum salmon virus, Closterovirus, Cocal virus, 65 alphaherpesvirus 2, human alphaherpesvirus 3, human B Coho Salmon reovirus, coital exanthema virus, Colorado tick lymphotropic virus, human betaherpesvirus 5, human coro fever virus, Coltivirus Columbia SK virus, Commelina yel navirus, Human enterovirus A, Human enterovirus B. Human US 8,647,676 B2 27 Flu, human foamy virus, humangammaherpesvirus 4., human Omsk hemorrhagic fever virus, oncogenic virus, oncogenic gammaherpesvirus 6, human hepatitis. A virus, human herp viruslike particle, oncornavirus, Orbivirus, Orf virus, esvirus 1 group, human herpesvirus 2 group, human herpes Oropouche virus, Orthohepadnavirus, orthomyxovirus, virus 3 group, human herpesvirus 4 group, human herpesvi Orthopoxvirus, Orthoreovirus, Orungo, ovine papillomavi rus 6, human herpesvirus 8, human immunodeficiency virus rus, Ovine catarrhal fever virus, owl monkey herpesvirus, (HIV), human immunodeficiency virus 1, human immunode Palyam virus, Papillomavirus, Papillomavirus Sylvilagi, ficiency virus 2, Human metapneumovirus, human papillo Papovavirus, Parainfluenza virus human (HPIV), parainflu mavirus, human T cell leukemia virus, human T cell leukemia enza virus type 1 human (HPIV-1), parainfluenza virus type 2 virus I, human T cell leukemiavirus II, human T cell leukemia human (HPIV-2), parainfluenza virus type 3 human (HPIV virus III, human T cell lymphoma virus I, human T cell 10 3), parainfluenza virus type 4 human (HPIV-4), Paramyxovii lymphoma virus II, human T cell lymphotropic virus type 1, rus, Parapoxvirus, paravaccinia virus, parsnip yellow fleck human T cell lymphotropic virus type 2, human T lympho virus, Parvovirus, Parvovirus B19, pea enation mosaic virus, tropic virus I, human T lymphotropic virus II, human T lym Pestivirus, Phlebovirus, phocine distemper virus, Phytoreovi photropic virus III, ichnovirus, larvirus, infantile gastroen rus, Picodnavirus, Picornavirus, pig cytomegalovirus, teritis virus, infectious bovine rhinotracheitis virus, 15 pigeonpox virus, Piry virus, Pixuna virus, plant rhabdovirus infectious haematopoietic necrosis virus, infectious pancre group, plant virus, virus of mice, Pneumovirus, atic necrosis virus, influenza virus, influenzavirus A, influen Poliomyelitis virus, Poliovirus, Polydnavirus, polyhedral Zavirus B, influenzavirus C, influenzavirus D, influenzavirus virus, Polyoma virus, Polyomavirus, Polyomavirus bovis, pr8, insect iridescent virus, insect virus, interfering virus, Polyomavirus cercopitheci, Polyomavirus hominis 2, Polyo iridovirus, Isavirus, Japanese B virus, Japanese encephalitis mavirus maccacae 1, Polyomavirus muris 1, Polyomavirus virus, JC virus, Junin virus, Johnson grass mosaic virus, muris 2, Polyomavirus papionis 1, Polyomavirus papionis 2. Kaposi's sarcoma-associated herpesvirus, Kemerovo virus, Polyomavirus Sylvilagi, Pongine herpesvirus 1, porcine epi Kilham's rat virus, Klamath virus, Kolongo virus, Korean demic diarrhea virus, porcine hemagglutinating encephalo hemorrhagic fever virus, kumba virus, Kumlinge virus, Kun myelitis virus, porcine parvovirus, porcine transmissible gas jin virus, Kyasanur forest disease, Kyzylagach virus, La 25 troenteritis virus, porcine type C virus, Potato leaf roll virus, Crosse virus, lactic dehydrogenase elevating virus, Lagos bat Potato mop top virus, Potato virus Y. Potexvirus, Potyvirus, virus, Lambda phage, langat virus, Langur virus, lapine par Powassan encephalitis virus, Poxvirus, poxvirus variolae, vovirus, Lassa fever virus, Lassa virus, latent rat virus, LCM Prospect Hill virus, provirus, pseudocowpox virus, pseudo virus, Leaky virus, Lentivirus, Leporipoxvirus, leukemia rabies virus, psittacinepox virus, Puumala virus, Qalyub virus, leukovirus, louping ill virus, lumpy skin disease virus, 30 virus, Quail pea mosaic virus, quailpox virus, Queensland Luteovirus, lymphadenopathy associated virus, Lymphocytic fruitfly virus, Quokkapox virus, rabbit fibroma virus, rabbit choriomeningitis virus (LCMV), Lymphocryptovirus, lym kidney vaculolating virus, rabbit papillomavirus, Rabies phocytic choriomeningitis virus, lymphoproliferative virus virus, raccoon parvovirus, raccoonpox virus, radish mosaic group, Lyssavirus, Machupo virus, mad itch virus, maize virus, Ranikhet virus, rat cytomegalovirus, rat parvovirus, rat chlorotic dwarf virus, maize rough dwarf virus, mammalian 35 virus, Rauscher's virus, recombinant vaccinia virus, recom type B oncovirus group, mammalian type B retroviruses, binant virus, Red Clover Necrotic Mosaic Virus, reovirus, mammalian type C retrovirus group, mammalian type D ret reovirus 1, reovirus 2, reovirus 3, reptilian type C virus, roviruses, mammary tumor virus, Mapuera virus, Marafivi Respiratory syncytial virus, respiratory virus, reticuloendot rus, Marburg virus, Marburg-like virus, Mason Pfizer mon heliosis virus, Retrovirus, Rhabdovirus, Rhabdovirus carpia, key virus, Mastadenovirus, Mayaro virus, ME virus, Measles 40 Rhadinovirus, Rhinovirus, Rhizidiovirus, rice dwarf virus, virus, Melandrium yellow fleck virus, Menangle virus, rice gall dwarf virus, rice hoja blanca virus, rice ragged stunt Mengo virus, Mengovirus, Merkel cell polyomavirus, Mid virus, Rift Valley fever virus, Riley's virus, rinderpest virus, delburg virus, milkers nodule virus, mink enteritis virus, RNA tumor virus, RNA virus, Roseolovirus, Ross River minute virus of mice, MLV related virus, MM virus, Mokola virus, Rotavirus, rougeole virus, Rous sarcomavirus, Rubella virus, Molluscipoxvirus, virus, 45 virus, rubeola virus, Rubivirus, Russian autumn encephalitis Moloney murine leukemia virus (M-MuDV), monkey B virus, S6-14-03 virus, SA 11 simian virus, SA 15, SA2 virus, virus, Monkeypox virus, Mononegavirales, Morbillivirus, SA6 virus, SA8 virus, Sabia virus, Sabio virus, Sabo virus, Mount Elgon bat virus, mouse cytomegalovirus, mouse Saboya virus, Sabulodes caberata GV, Sacbrood virus, Sac encephalomyelitis virus, mouse hepatitis virus, mouse K charomyces cerevisiae virus L-A, Saccharomyces cerevisiae virus, mouse leukemia virus, mouse mammary tumor virus, 50 virus La, Saccharomyces cerevisiae virus LBC, Sagiyama mouse minute virus, mouse pneumonia virus, mouse polio virus, Saguaro cactus virus, aimiriine herpesvirus 1, Saimiri myelitis virus, mouse polyomavirus, mouse sarcoma virus, ine herpesvirus 2, Sainpaulia leaf necrosis virus, SaintAbb's mousepox virus, Mozambique virus. Mucambo virus, Head virus, Saint-Floris virus, Sakhalin virus, Sal Vieja virus, mucosal disease virus, Mumps virus, murid betaherpesvirus Salanga virus, Salangapox virus, Salehabad virus, Salivary 1, murid cytomegalovirus 2, murine cytomegalovirus group, 55 gland virus, Salmonid herpesvirus 1, Salmonid herpesvirus 2, murine encephalomyelitis virus, murine hepatitis virus, Salmonis virus, Sambucus vein clearing virus, Samia cynthia murine leukemia virus, murine nodule inducing virus, murine NPV. Samia pryeri NPV. Samia ricini NPV. Sammons polyomavirus, murine sarcoma virus, Muromegalovirus, Opuntia virus, SanAngelo virus, San Juan virus, San Miguel Murray Valley encephalitis virus, myxoma virus, Myxovirus, sealion virus, San Perlita virus, Sand rat nuclear inclusion Myxovirus multiforme, Myxovirus parotitidis, Nairobi sheep 60 agents, Sandfly fever Naples virus, Sandfly fever Sicilian disease virus, Nairovirus, Nanirnavirus, Narivavirus, Ndumo virus, Sandjimba virus, Sango virus, Santa Rosa virus, San virus, Necrovirus, Neethling virus, Nelson Bay virus, Nem tarem virus, Santosai temperate virus, Sapphire II virus, Sap tickVirus, Nepovirus, neurotropic virus, New World Arenavi poro-like virus, Saraca virus, Sarracenia purpurea virus, rus, newborn pneumonitis virus, Newcastle disease virus, SARS virus, satellite virus, Sathuperi virus, Satsuma dwarf Nipah virus, noncytopathogenic virus, Norovirus, Norwalk 65 virus, Saturnia pavonia virus, Saturnia pyri NPV. Saumarez virus, nuclear polyhedrosis virus (NPV), nipple neck virus, O' Reef virus, Sawgrass virus, Sceliodes cordalis NPV. Schef nyongnyong virus, oat sterile dwarf virus, Ockelbo virus, flera ringspot virus, Sciaphila duplex GV, Scirpophaga US 8,647,676 B2 29 30 incertulas NPV. Sciurid herpesvirus, Sciurid herpesvirus 2, virus, Statice virus Y. P. STLV (simian T lymphotropic virus) Scoliopteryx libatrix NPV. Scopelodes contracta NPV. type I, STLV (simian T lymphotropic virus) type II, STLV Scopelodes venosa NPV. Scopula subpunctaria NPV. Scoto (simian T lymphotropic virus) type III, stomatitis papulosa gramma trifolii GV, Scotogramma trifolu NPV. Scrophularia virus, Stratford virus, Strawberry crinkle virus, Strawberry mottle virus, SDAV (sialodacryoadenitis virus), sealpox latent ringspot virus, Strawberry mild yellow edge virus, virus, Selenephera lunigera NPV. Selepa celtis GV, Seletar Strawberry vein banding virus, Streptococcus phage 182, virus, Selidosema Suavis NPV, Semidonta biloba NPV. Streptococcus phage 2BV. Streptococcus phage A25, Strep Semiothisa sexmaculata GV, Semliki Forest Virus, Sena tococcus phage 24, Streptococcus phage PE1, Streptococcus Madureira virus, Sendai virus, SENV-D, SENV-H, Seoul phage VD13, Streptococcus phage fl)8, Streptococcus phage virus, Sepik virus, Serra do Navio virus, Serrano golden 10 CP-1, Streptococcus phage Cvir, Streptococcus phage H39, mosaic virus, Sesame yellow mosaic virus, Sesamia calam Strigid herpesvirus 1, Striped bass reovirus, Striped Jack istis NPV. Sesamia Cretica GV, Sesamia inferens NPV. Sesa nervous, necrosis virus, Stump-tailed macaque virus, Sub mia nonagrioides GV, Setora nitens virus, Shallot latent maxillary virus, Subterranean clover mottle virus, Subterra virus, Shamonda virus, Shark River virus, Sheep associated nean clover mottle virus satellite, Subterranean cloverred leaf malignant catarrhal fever, Sheep papillomavirus, Sheep pull 15 virus, Subterranean clover stunt virus, Sugarcane bacilliform monary adenomatosis associated herpesvirus, sheeppox virus, Sugarcane mild mosaic virus, Sugarcane mosaic virus, virus, Shiant Islands virus, Shokwe virus, Shope fibroma Sugarcane streak virus, Suid alphaherpesvirus 1, Suid herpes virus, Shope papilloma virus, Shuni virus, Siamese cobra virus 2, Suipoxvirus, Sulfolobus virus 1, Sunday Canyon herpesvirus, Sibine fusca densovirus, Sida golden mosaic virus, Sunflower crinkle virus, Sunflower mosaic virus, Sun virus (SiGMV), Sida golden yellow vein virus (SiGYVV), flower rugose mosaic virus, Sunflower yellow blotch virus, Sigma virus, Sikte water-borne virus, Silverwater virus, Sunflower yellow ringspot virus, Sun-hemp mosaic virus, Simbu virus, Simian adenoviruses 1 to 27, Simian agent virus swamp fever virus, Sweet clover necrotic mosaic virus, Sweet 12, Simian enterovirus 1 to 18, simian foamy virus, Simian potato A virus, Sweet potato chlorotic leafspot virus, Sweet hemorrhagic fever virus, simian hepatitis A virus, simian potato feathery mottle virus, Sweet potato internal cork virus, human immunodeficiency virus, simian immunodeficiency 25 Sweet potato latent virus, Sweet potato mild mottle virus, virus, simian parainfluenza virus, Simian rotavirus SA11. Sweet potato russet crack virus, Sweet potato vein mosaic Simian sarcoma virus, simian T cell lymphotrophic virus, virus, Sweet potato yellow dwarf virus, Sweetwater Branch Simian type D virus 1, Simian Vancella herpesvirus, simian virus, Swine cytomegalovirus, Swine Flu, Swine infertility virus, simian virus 40, Simplexvirus, Simulium vittatum and respiratory syndrome virus, Swinepox virus, Swiss densovirus, Sin Nombre virus, Sindbis virus, Sintlems 30 mouse leukemia virus, Sword bean distortion mosaic virus, onion latent virus, Sixgun city virus, Skunkpox virus, Small Synaxis jubararia NPV. Synaxis pallulata NPV. Synetaeris pox virus, Smelt reovirus, Smerinthus ocellata NPV. Smithi tenuifemur virus, Syngrapha selecta NPV. T4 phage. T7 antha virus, Snakehead rhabdovirus, Snowshoe hare virus, phage, TAC virus, Tacaiuma virus, Tacaribe complex virus, Snyder-Theilen feline sarcoma virus, Sobemovirus, Sofyn Tacaribe virus, Tadpole edema virus LT 1-4, Taggert virus, virus, Soil-borne wheat mosaic virus, Sokoluk virus, 35 Tahyna virus, Tai virus, TaiasSui virus, Tamana bat virus, Solanum apical leaf curl virus, Solanum modiflorum mottle Tamarillo mosaic virus, Tamdy virus, Tamiami virus, virus, Solanurn yellows virus, Soldado virus. Somerville Tanapox virus, Tanga virus, Tanjong Rabok virus, Taro bacil virus 4, Sonchus mottle virus, Sonchus virus, Sonchus yellow liform virus, Badnavirus Tataguine virus, Taterapox virus, net virus, Sorghum chlorotic spot virus, Sorghum mosaic Taterapox virus, Teasel mosaic virus, Tehran virus, Telfairia virus, Sorghum virus, Sororoca virus, Soursop yellow blotch 40 mosaic virus, Telok Forest virus, Tembe virus, Tembusu virus, South African passiflora virus, South American hem virus, Tench reovirus, Tensaw virus, Tenvivirus, Tephrosia orrhagic fever viruses, South African passiflora virus, South symptomless virus, Termeil virus, Tete virus, Tetralopha River virus, Southern bean mosaic virus, Southern potato scortealis NPV. Tetropium cinnamopterum NPV. Texas pep latent virus, Sowbane mosaic virus, Sowthistle yellow vein per virus, Thailand virus, Thaumetopoea pityocampa virus, virus, Soybean chlorotic mottle virus, Soybean crinkle leaf 45 Theiler’s encephalomyelitis virus. Theiler's virus. Theophila virus, Soybean dwarf virus, Soybean mosaic virus, SPAr mandarina NPV. Theretra japonica NPV. Thermoproteus 2317 virus, Sparganothis pettitana NPV, sparrowpox virus, virus 1, Thermoproteus virus 2, Thermoproteus virus 3, Ther Spartina mottle virus, Spectacled caimanpox virus, SPH moproteus virus 4. Thiafora virus. Thimiri virus. Thistle 114202 virus, Sphenicid herpesvirus 1, Sphinx ligustri NPV. mottle virus, Thogoto virus, Thormodseyjarklettur virus, Spider monkey herpesvirus, Spilarctia subcarnea NPV. Spi 50 Thosea asigna virus, Thosea baibarana NPV. Thosea sinen lonota ocellana NPV. Spilosoma lubricipeda NPV. Spinach sis GV, Thottapalayam virus, Thylidolpteryx ephemeraefor latent virus, Spinach temperate virus, Spiroplasma phage 1, mis NPV. Thymelicus lineola NPV. Tilbrogargan virus, Ticera Spiroplasma phage 4, Spiroplasma phage aa, Spiroplasma castanea NPV. Tick borne encephalitis virus (TBEV)—Eu phage C1/T52, Spodoptera exempta cypovirus, Spodoptera ropean and Far Eastern subtypes, Tillamook virus, Tilligerry exigua virus, Spodoptera frugiperda virus, Spodoptera lati 55 virus, Timbo virus, Tilmboteua virus, Tilmaroo virus, Tind fascia virus, Spodoptera littoralis, Spodoptera mauritia holmur virus, Tinea pellionella NPV. Tineola hisselliella virus, Spodoptera Ornithogalli virus, Spondweni virus, NPV. Tinpula paludosa NPV. Timracola plagiata NPV. spring beauty latent virus, Spring viremia of carp virus, Spu Tioman virus, Tlacotalpan virus, Tobacco bushy top virus, mavirus (SFV. HFV), Squash leaf curl virus, squash mosaic Tobacco etch virus, Tobacco leaf curl virus, Tobacco mild virus, squirrel fibroma virus, Squirrel monkey herpesvirus, 60 green mosaic virus, tobacco mosaic virus, Tobacco mosaic squirrel monkey retrovirus, SR-11 virus, Sri Lankan passion virus satellite, Tobacco mottle virus, Tobacco necrosis virus, fruit mottle virus, Sripur virus, SSV 1 virus group, StAbbs Tobacco necrosis virus satellite, Tobacco necrosis virus Small Head virus, St. Louis encephalitis virus, Staphylococcus satellite, Tobacco necrotic dwarf virus, tobacco rattle virus, phage 107, Staphylococcus phage 187. Staphylococcus Tobacco ringspot virus, Tobacco streak virus, Tobacco stunt phage 2848A, Staphylococcus phage 3A, Staphylococcus 65 virus, Tobacco vein banding mosaic virus, Tobacco vein dis phage 44A HJD, Staphylococcus phage 77, Staphylococcus torting virus Tobacco vein mottling virus, Tobacco wilt virus, phage B11-M15, Staphylococcus phage Twort, Starlingpox Tobacco yellow dwarf virus, Tobacco yellow net virus, US 8,647,676 B2 31 32 Tobacco yellow vein virus, Tobamovirus Tobravirus, Togavi mosaic virus 2, Weddel water-borne virus, Weldona virus, rus, Tomato apical stunt Viroid, Tomato aspermy virus, Wesselsbron virus, West Nile virus, western equine encepha Tomato black ring virus, Tomato black ring virus satellite, litis virus, western equine encephalomyelitis virus, Wexford Tomato bunchy top viroid, tomato bushy stunt Virus, Tomato virus, Whataroa virus, Wheat American striate mosaic virus, bushy stunt virus satellite, Tomato golden mosaic virus, Wheat chlorotic streak virus, Wheat dwarf virus, Wheat Tomato leaf crumple virus, Tomato leaf curl virus, Tomato rosette stunt virus, Wheat streak mosaic virus. Wheat yellow leafroll virus, Tomato mosaic virus, Tomato mottle virus, leaf virus, Wheat yellow mosaic virus, White bryony virus, Tomato pale chlorosis virus, Tomato planta macho Viroid, White clover cryptic virus 1, White clover cryptic virus 2, Tomato pseudo-curly top virus, Tomato ringspot virus, White clover cryptic virus 3, White clover mosaic virus, Tomato spotted wilt virus, Tomato top necrosis virus, Tomato 10 vein yellowing virus, Tomato yellow dwarf virus, Tomato White lupinrnosaic virus, Wild cucumber mosaic virus, Wild yellow leaf curl virus, Tomato yellow mosaic virus, Tomato potato mosaic virus, Wildbeest herpesvirus, Wineberry latent yellow top virus, Tombusvirus, Tongan vanilla virus, Torovi virus, Winter wheat mosaic virus, Winter wheat Russian rus, Torque teno virus, Tortrix loeflingiana NPV. Tortrix viri mosaic virus, Wiseana cervinata virus, Wiseana signata dana NPV. Toscana virus, Tospovirus, Toxorhynchites brevi 15 virus, Wiseana umbraculata virus, Wissadula mosaic virus, palpis NPV. Trabala vishnou NPV. Tradescantia/Zebrina Wisteria vein mosaic virus. Witwatersrand virus, Wongal virus, Trager duck spleen necrosis virus, Tranosema sp. Virus, virus, Wongorr virus, Winter Vomiting Virus, woodchuck transforming virus, Tree shrew adenovirus 1, Tree shrew her hepatitis B virus, Woodchuck herpesvirus marmota 1, woolly pesvims, Triatoma virus, Tribec virus, Trichiocampus irregu monkey sarcoma virus, wound tumor virus, WRSV virus, laris NPV. Trichiocampus viminalis NPV. Trichomonas vagi WVU virus 2937, WW virus 71 to 212, Wveomyia Smithii nalis virus, Trichoplusia ni cypovirus 5, Trichoplusia ni NPV. Wyeomyia virus, Xanthomonas phage Cf, Xanthomo granulovirus, Trichoplusia ni MNPV. Trichoplusia ni Single nas phage Cflt, Xanthomonas phage RR66, Xanthomonas SNPV. Trichoplusia ni virus, Trichosanthes mottle virus, phage Xf, Xanthomonas phage Xf2, Xanthomonas phage Triticum aestivum chlorotic spot virus, Trivittatus virus, XP5, Xenopus virus T21, Xiburema virus, Xingu virus, Trombetas virus, Tropaeolum virus 1, Tropaeolum virus 2, 25 Xylena curvimacula NPV.Y73 sarcoma virus, Yaba monkey Trubanarnan virus, Tsuruse virus, Tucunduba virus, Tulare tumor virus, Yaba-1 virus, Yaba-7 virus, Yacaaba virus, Yam apple mosaic virus, Tulip band breaking virus, Tulip breaking mosaic virus, Yaounde virus, Yaquina Head virus, Yatapoxvi virus, Tulip chlorotic blotch virus, Tulip top breaking virus, rus, Yellow fever virus, Yogue virus, Yokapox virus, Yokase Tulip virus X, tumor virus, Tupaia virus, Tupaiid herpesvirus virus, Yponomeuta cognatella NPV, Yponomeuta evonymella 1, Turbotherpesvirus, Turbot reovirus, Turkey adenoviruses 1 30 NPV. Yponomeuta malinellus NPV, Yponomeuta padella to 3, Turkey coronavirus, Turkey herpesvirus 1, turkey rhi NPV, Yucca baciliform virus, Yug Bogdanovac virus, Zaliv notracheitis virus, turkeypox virus, Turlock virus, Turnip Terpeniya virus, Zea mays virus, Zegla virus, Zeiraphera crinkle virus, Turnip crinkle virus satellite, Turnip mild yel diniana virus, Zeiraphera pseudotsugana NPV. , lows virus, Turnip mosaic virus, Turnip rosette virus, turnip Zirqa virus, Zoysia mosaic virus, Zucchiniyellow fleck virus, yellow mosaic virus, Turuna virus, Tymovirus, Tyuleniy 35 Zucchini yellow mosaic virus, and Zygocactus virus. virus, type Cretroviruses, type Doncovirus, type D retrovirus In one embodiment the antimicrobial composition accord group, Uasin Gishu disease virus, Uganda S virus, Ugymyia ing to the present invention is used to inhibit, kill, and/or sericariae NPV, ulcerative disease rhabdovirus, Ullucus mild prevent the growth of one or more fungi, such as those mottle virus, Ullucus mosaic virus, Ullucus virus C, Umatilla described elsewhere in the application. virus, Umbre virus, Una virus. Upolu virus, UR2 sarcoma 40 The antimicrobial composition can also be used as an anti virus, Uranotaenia sapphirina NPV. Urbanus proteus NPV. microbial detergent, an antimicrobial hand wash, an antimi Urucuri virus, Ustilago maydis virus 1, Ustilago maydis virus crobial toothpasta, an antimicrobial mouthwash, an antimi 4, Ustilago maydis virus 6. Usutu virus, Uting a virus, Utive crobial textile treatment etc. virus, Uukuniemi virus group, Vaccinia virus, Vaeroy virus, Use of the Composition from C. finmarchicus as a Pharma Vallota mosaic virus, Vanessa atalanta NPV. Vanessa cardui 45 ceutical NPV. Vanessa prorsa NPV. Vanilla mosaic virus, Vanilla In one embodiment, the present invention relates to a phar necrosis virus, Varicella Zoster virus, Varicellovirus, Varicola maceutical composition obtained from Calanus finnarchi virus, variola major virus, variola virus, Vasin Gishu disease C.S. virus, Vellore virus, Velvet tobacco mottle virus, Velvet The composition obtained from Calanus finnarchicus can tobacco mottle virus satellite, Venezuelan equine encephalitis 50 in one embodiment of the present invention be used as a virus, Venezuelan equine encephalomyelitis virus, Venezu medicament. elan hemorrhagic fever virus, Vesicular stomatitis virus, In one embodiment of the present invention a composition Vesiculovirus, Vibriophage 06N-22P, Vibrio phage 06N-58P. obtained from Calanus finnarchicus is used in the treatment Vibrio phage 4996, Vibrio phagea3a, Vibrio phage I, Vibrio of microbial infections in an individual in need thereof. phage II, Vibrio phage m, Vibrio phage IV, Vibrio phage 55 In another embodiment the composition obtained from kappa, Vibrio phage int-1, Vibrio phage OXN-52P. Vibrio Calanus finnarchicus is used for the manufacture of a medi phage OXN-IOOP, Vibriophage v6, Vibriophage Vfl2, Vibrio cament for the treatment microbial infections. phage Vf33, Vibrio phage VP1, Vibrio phage VP11, Vibrio The treatment can be ameliorating, curative or prophylac phage VP3, Vibrio phage VP5, Vibrio phage X29, Vicia cryp tic treatment of one or more infectious diseases. tic virus, Vigna Sinensis mosaic virus, Vilyuisk virus, Vinces 60 An infectious disease is in one embodiment a clinically virus, Viola mottle virus, viper retrovirus, viral haemorrhagic evident disease resulting from the presence of pathogenic septicemia virus, virus-like particle, Visna Maedi virus, Visna agents, including pathogenic viruses, pathogenic bacteria, virus, Voandzeia mosaic virus, Voandzeia necrotic mosaic fungi, , multicellular parasites, and aberrant proteins virus, volepox virus, Wad Medanivirus, Wallal virus, Walleye known as prions. These pathogens are able to cause disease in epidermal hyperplasia, Walrus calicivirus, Wanowrie virus, 65 human beings, animals and/or plants. Microbial infections Warrego virus, Watermelon chlorotic stunt virus, Watermelon include infections caused by bacteria, fungi, protozoans, and curly mottle virus, Watermelon mosaic virus 1, Watermelon viruses. US 8,647,676 B2 33 34 Infectious pathologies are usually qualified as contagious genes, Aeromonas euchrenophila, Aeromonas hydrophila, diseases (also called communicable diseases) due to their Aeromonas ichthiosmia, Aeromonas jandaei, Aeromonas potentiality of transmission from one person or species to media, Aeromonas molluscorum, Aeromonas popoffii, Aero another. Transmission of an infectious disease may occur monas punctata, Aeromonas Salmonicida, Aeromonas Schu through one or more of diverse pathways including physical bertii, Aeromonas Sharmana, Aeromonas simiae, Aeromonas contact with infected individuals. These infecting agents may sobria, Aeromonas veronii, Afipia felis, Agrobacterium spe also be transmitted through liquids, food, body fluids, con cies: Agrobacterium radiobacter, Agrobacterium rhizogenes, taminated objects, airborne inhalation, or through vector Agrobacterium rubi, Agrobacterium tumefaciens, Agrono borne spread. nas species, Alcaligenes species: Alcaligenes aquatilis, The term infectivity describes the ability of an organism to 10 Alcaligenes eutrophus, Alcaligenes faecalis, Alcaligenes enter, survive and multiply in the host, while the infectious latus, Alcaligenes xylosoxidans, Alishewanella species, ness of a disease indicates the comparative ease with which Alterococcus species, Anaplasma phagocytophilum, Ana the disease is transmitted to other hosts. An infection is not plasma marginale, Aquamonas species, Arcanobacterium synonymous with an infectious disease, as an infection may haemolyticum, Aranicola species, Arsenophonus species, not cause important clinical symptoms or impair host func 15 Azotivirga species, Azotobacter vinelandii, Azotobacter tion. chroococcum, (Shigellosis), Bacillus In a preferred embodiment the present invention relates to species: Bacillus abortus (Brucella melitensis biovar abor treatment of bacterial infections. tus), Bacillus anthracis (Anthrax), Bacillus brevis, Bacillus In another preferred embodiment, the present invention cereus, Bacillus coagulans, Bacillus fusiformis, Bacillus glo relates to treatment of fungal infections. bigii, Bacillus licheniformis, Bacillus megaterium, Bacillus In another embodiment, the present invention relates to mycoides, Bacillus natto, Bacillus Stearothermophilus, treatment of viral infections. Bacillus subtilis, Bacillus sphaericus, Bacillus thuringiensis, Bacteria Bacteroides species: Bacteroides forsythus (Tannerella for In one embodiment, the composition of the present inven sythensis), Bacteroides acidifaciens, Bacteroides distasonis tion is directed against a bacteria, i.e. it is antibacterial or an 25 (reclassified as Parabacteroides distasonis), Bacteroides gin antibiotic. givalis, Bacteroides gracilis, Bacteroides fragilis, Bacteroi In one embodiment the antimicrobial composition of the des Oris, Bacteroides ovatus, Bacteroides putredinis, present invention can be used as a broad-spectrum antibiotic. Bacteroides pyogenes, Bacteroides Stercoris, Bacteroides In one embodiment, the antibacterial activity is directed suis, Bacteroides tectus, Bacteroides thetaiotaomicron, against one or more bacteria selected from the group consist 30 Bacteroides vulgatus, Bartonella species: Bartonella ing of Gram positive bacteria, Gram negative bacteria, aero alsatica, Bartonella bacilliformis, Bartonella birtlesii, Bar bic bacteria, anaerobic bacteria. tonella bovis, Bartonella capreoli, Bartonella clarridgeiae, In one embodiment the composition according to the Bartonella doshiae, Bartonella elizabethae, Bartonella gra present invention can be used for treatment of one or more hamii, Bartonella henselae (cat scratch fever), Bartonella diseases caused one or more bacteria Such as one or more of 35 koehlerae, Bartonella muris, Bartonella peromysci, Bar the bacteria selected from the group consisting of Aceto tonella quintana, Bartonella rochalinae, Bartonella Schoen– bacter aurantius, Acinetobacter species: Acinetobacter bau buchii, Bartonella talpae, Bartonella taylorii, Bartonella tri mannii, Acinetobacter calcoaceticus, Acinetobacter johnso bocorum, Bartonella vinsonii spp. Arupensis, Bartonella nii, Acinetobacter junii, Acinetobacter lwofii, Acinetobacter vinsonii spp. Berkhofii, Bartonella vinsonii spp. Vinsonii, radio resistens, Acinetobacter septicus, Acinetobacter schin 40 Bartonella washoensis; BCG (Bacille Calmette-Guerin), dleri, Acinetobacter ursingii; Actinomyces species: Actino Bergeyella zoohelicum (Weeksella zoo helcium), Bifidobacte myces bovis, Actinomyces bowdenii, Actinomyces canis, Acti rium bifidum, Blastobacter species, Blochmannia species, nomyces cardiffensis, Actinomyces Catuli, Actinomyces Bordetella species: Bordetella ansorpii, Bordetella avium, coleocanis, Actinomyces dentalis, Actinomyces denticolens, Bordetella bronchiseptica, Bordetella hinzii, Bordetella Actinomyces europaeus, Actinomyces funkei, Actinomyces 45 holmesii, Bordetella parapertussis, Bordetella pertussis georgiae, Actinomyces gerencseriae, Actinomyces grae (Whooping cough), Bordetella petri, Bordetella trematum, venitzii, Actinomyces hongkongensis, Actinomyces hordeo Borrelia species: Borrelia burgdorferi, Borrelia afzelii, Bor vulneris, Actinomyces howellii, Actinomyces humiferus, Acti relia anserina, Borrelia garinii, Borrelia valaisiana, Borrelia nomyces hyovaginalis, Actinomyces israelii, Actinomyces hermsii, Borrelia Parkeri, Borrelia recurrentis, Bosea spe marinammalium, Actinomyces meyeri, Actinomyces 50 cies, Bradyrhizobium species, Brenneria species, Brucella naeslundii, Actinomyces nasicola, Actinomyces neuii, Acti species: Brucella abortus, Brucella Canis, Brucella meliten nomyces Odontolyticus, Actinomyces Oricola, Actinomyces sis, Brucella neotomae, Brucella ovis, Brucella suis, Brucella radicidentis, Actinomyces radingae, Actinomyces slackii, pinnipediae, Buchnera species, Budvicia species, Burkhold Actinomyces Streptomycini, Actinomyces suinastitidis, Acti eria species: Burkholderia cepacia (Pseudomonas cepacia), nomyces suis, Actinomyces turicensis, Actinomyces urogeni 55 Burkholderia mallei (Pseudomonas mallei/Actinobacillus talis, Actinomyces vaccinaxillae, Actinomyces viscosus, mallei), Burkholderia pseudomallei (Pseudomonas Actinobacillus species: Actinobacillus actinomycetemcomi pseudomalilei); Buttiauxella species, Calymmatobacterium tans, Actinobacillus arthritidis, Actinobacillus capsulatus, granulomatis, Campylobacter species: Campylobacter coli, Actinobacillus delphinicola, Actinobacillus equuli, Actino Campylobacter concisus, Campylobacter curvus, Campylo bacillus hominis, Actinobacillus indolicus, Actinobacillus 60 bacter fetus, Campylobacter gracilis, Campylobacter hel lignieresi, Actinobacillus minor; Actinobacillus muris, Acti veticus, Campylobacter hominis, Campylobacter hyointesti nobacillus pleuropneumoniae, Actinobacillus porcinus, Acti nalis, Campylobacter insulaenigrae, Campylobacter jejuni, nobacillus rossii, Actinobacillus Scotiae, Actinobacillus Campylobacter lanienae, Campylobacter lari, Campylo seminis, Actinobacillus succinogenes, Actinobacillus suis, bacter mucosalis, Campylobacter rectus, Campylobacter Actinobacillus ureae, Aeromonas species: Aeromonas 65 Showae, Campylobactersputorum, Campylobacter upsalien allosaccharophila, Aeromonas bestiarum, Aeromonas sis, Capnocytophaga canimorsus (Dysgonic fermenter type bivalvium, Aeromonas encheleia, Aeromonas enteropelo 2), Corynebacterium species, Cardiobacterium hominis, US 8,647,676 B2 35 36 Cedecea species, Chlamydia species: Chlamydia trachoma niae, Haemophilus Somnus, Haemophilus vaginalis, Hafinia tis (Lymphogranuloma Venereum), Chlamydia muridarum, species, Hafnia alvei, Helicobacter species: Helicobacter Chlamydia suis, Chlamydophila species: Chlamydophila acinonychis, Helicobacter anseris, Helicobacter aurati, pneumoniae, Chlamydophila psittaci (Psittacosis), Chlamy Helicobacter bilis, Helicobacter bizzozeronii, Helicobacter dophila pecorum, Chlamydophila abortus, Chlamydophila brantae, Helicobacter Canadensis, Helicobacter canis, Heli felis, Chlamydophila caviae, Citrobacter species: Citro cobacter cholecystus, Helicobacter cinaedi, Helicobacter bacter amalonaticus, Citrobacter braakii, Citrobacter farm cynogastricus, Helicobacter felis, Helicobacter fennelliae, eri, Citrobacter freundii, Citrobacter gillenii, Citrobacter Helicobacterganmani, Helicobacter heilmannii (Gastrospir intermedius, Citrobacter koseri aka Citrobacter diversus, illum hominis), Helicobacter hepaticus, Helicobacter Citrobacter murliniae, Citrobacter rodentium, Citrobacter 10 mesocricetorum, Helicobacter marmotae, Helicobacter Sedlaki, Citrobacter werkmanii, Citrobacter youngae, muridarum, Helicobacter mustelae, Helicobacter pameten Clostridium species: Clostridium botulinum, Clostridium dif sis, Helicobacter pullorum, Helicobacter pylori (stomach ficile, Clostridium novyi, Clostridium septicum, Clostridium ulcer), Helicobacter rappini, Helicobacter rodentium, Heli tetani (Tetanus), Clostridium welchii (Clostridium perfirin cobacter Salomonis, Helicobacter trogontum, Helicobacter gens); Corynebacterium species: Corynebacterium diphthe 15 typhlonius, Helicobacter winghamensis; Human granulo riae (Diphtheria), Corynebacterium amycolatum, Coryne cytic ehrlichiosis (Anaplasma phagocytophilum/Ehrlichia bacterium aquaticum, Corynebacterium bovis, phagocytophila), Human monocytotropic ehrlichiosis Corynebacterium equi, Corynebacterium flavescens, (Monocytic ehrlichiosis/Ehrlichia chafeensis), Klebsiella Corynebacterium glutamicum, Corynebacterium haemolyti species: Klebsiella granulomatis (Calymmatobacterium cum, Corynebacterium jeikeiun (corynebacteria of group granulomatis), Klebsiella mobilis, Klebsiella Ornithinolytica, JK), Corynebacterium minutissimum (Erythrasma), Coryne Klebsiella Oxytoca, Klebsiella Ozaenae, Klebsiella planti bacterium parvum (also called Propionibacterium acnes), cola, Klebsiella pneumoniae, Klebsiella rhinoscleromatis, Corynebacterium pseudodiptheriticum (also called Coryne Klebsiella Singaporensis, Klebsiella terrigena, Klebsiella bacterium hofinannii), Corynebacterium pseudotuberculosis trevisani, Klebsiella varicola, Kingella kingae, Kluyvera (also called Corynebacterium Ovis), Corynebacterium pyo 25 species, Lactobacillus species: Lactobacillus acetotolerans, genes, Corynebacterium urealyticum (corynebacteria of Lactobacillus acidifarinae, Lactobacillus acidipiscis, Lacto group D2), Corynebacterium renale, Corynebacterium stria bacillus acidophilus (Doderlein bacillus), Lactobacillus agi tum, Corynebacterium tenuis (Trichomycosis palmellina, Tri lis, Lactobacillus algidus, Lactobacillus alimentarius, Lac chomycosis axillaris), Corynebacterium ulcerans, Coryne tobacillus amylolyticus, Lactobacillus amylophilus, bacterium xerosis, Coxiella burnetii (), Cronobacter 30 Lactobacillus amylotrophicus, Lactobacillus amylovorus, species: Cronobacter Sakazakii, Cronobacter malonaticus, Lactobacillus animalis, Lactobacillus antri, Lactobacillus Cronobacter turicensis, Cronobacter muytjensii, Crono apodemi, Lactobacillus aviarius, Lactobacillus bifermen bacter dublimensis, Delftia acidovorans (Comamonas aci tans, Lactobacillus brevis, Lactobacillus buchneri, Lactoba dovorans), Dickeya species, Edwardsiella species, Eikenella cillus camelliae, Lactobacillus casei, Lactobacillus cat corrodens, Enterobacter species: Enterobacter aerogenes, 35 enaformis, Lactobacillus ceti, Lactobacillus coleohominis, Enterobacter cloacae, Enterobacter Sakazakii Enterococcus Lactobacillus collinoides, Lactobacillus composti, Lactoba species: Enterococcus avium, Enterococcus durans, Entero cillus concavus, Lactobacillus coryniformis, Lactobacillus coccus faecalis (Streptococcus faecalis/Streptococcus Group crispatus, Lactobacillus crustorum, Lactobacillus curvatus, D), Enterococcus faecium, Enterococcus solitarius, Entero Lactobacillus delbrueckii, Lactobacillus delbrueckii subsp. coccus gallinarum, Enterococcus maloratus, Ehrlichia 40 Bulgaricus, Lactobacillus delbrueckii Subsp. Lactis, Lacto chafeensis, Erysipelothrix rhusiopathiae, Erwinia species, bacillus diolivorans, Lactobacillus equi, Lactobacillus Escherichia species: Escherichia adecarboxylata, Escheri equigenerosi, Lactobacillus farraginis, Lactobacillus far chia albertii, Escherichia blattae, Escherichia coli, Escheri ciminis, Lactobacillus fermentum, Lactobacillus formicalis, chia fergusonii, Escherichia hermannii, Escherichia vuln Lactobacillus fructivorans, Lactobacillus frumenti, Lactoba eris, Ewingella species, Flavobacterium species: 45 cillus fitchuensis, Lactobacillus gallinarum, Lactobacillus Flavobacterium aquatile, Flavobacterium branchiophilum, gasseri, Lactobacillus gastricus, Lactobacillus ghanensis, Flavobacterium columnare, Flavobacterium flevense, Fla Lactobacillus graminis, Lactobacillus hammesii, Lactobacil vobacterium gondwanense, Flavobacterium hydatis, Fla lus hamsteri, Lactobacillus harbinensis, Lactobacillus haya vobacterium johnsoniae, Flavobacterium pectinovorum, kitensis, Lactobacillus helveticus, Lactobacillus hilgardii, Flavobacterium psychrophilum, Flavobacterium saccharo 50 Lactobacillus homohiochii, Lactobacillus iners, Lactobacil philum, Flavobacterium salegens, Flavobacterium scoph lus inglu viei, Lactobacillus intestinalis, Lactobacillus jens thalmum, Flavobacterium succinans, Francisella tularensis enii, Lactobacillus johnsonii, Lactobacillus kalixensis, Lac (Tularaemia), Francisella novicida, Francisella philomira tobacillus kefiranofaciens, Lactobacillus Refiri, gia, Fusobacterium species: Fusobacterium necrophorum Lactobacillus kimchii, Lactobacillus kitasatonis, Lactobacil (Lemierre Syndrome/Sphaerophorus necrophorus), Fuso 55 lus kunkeei, Lactobacillus leichmannii, Lactobacillus lind bacterium nucleatum, Fusobacterium polymorphum, Fuso neri, Lactobacillus malefermentans, Lactobacillus mali, Lac bacterium novum, Fusobacterium mortiferum, Fusobacte tobacillus manihotivorans, Lactobacillus mindensis, rium varium, Gardnerella vaginalis, Gemella haemolysans, Lactobacillus mucosae, Lactobacillus murinus, Lactobacil Gemella morbillorum (Streptococcus morbillorum), Gri lus nagelii, Lactobacillus namurensis, Lactobacillus manten montella species, Haemophilus species: Haemophilus aegyp 60 sis, Lactobacillus Oligofermentans, Lactobacillus Oris, Lac tius (Koch-Weeks bacillus), Haemophilus aphrophilus, Hae tobacillus panis, Lactobacillus pantheris, Lactobacillus mophilus avium, Haemophilus ducreyi (Chancroid), parabrevis, Lactobacillus parabuchneri, Lactobacillus para Haemophilus felis, Haemophilus haemolyticus, Haemophi collinoides, Lactobacillus parafarraginis, Lactobacillus par lus influenzae (Pfeiffer bacillus), Haemophilus paracunicu akefiri, Lactobacillus parallimentarius, Lactobacillus para lus, Haemophilus parahaemolyticus, Haemophilus parain 65 plantarum, Lactobacillus pentosus, Lactobacillus perolens, fluenzae, Haemophilus paraphrophilus (Aggregatibacter Lactobacillus plantarum, Lactobacillus pontis, Lactobacil aphrophilus), Haemophilus pertussis, Haemophilus pittma lus psittaci, Lactobacillus rennini, Lactobacillus reuteri, US 8,647,676 B2 37 38 Lactobacillus rhamnosus, Lactobacillus rimae, Lactobacil Mycobacterium agri, Mycobacterium aichiense, Mycobacte lus rogosae, Lactobacillus rossiae, Lactobacillus ruminis, rium alvei, Mycobacterium arupense, Mycobacterium asiati Lactobacillus Saerimneri, Lactobacillus sakei, Lactobacillus cum, Mycobacterium aubagnense, Mycobacterium aurum, salivarius, Lactobacillus Sanfranciscensis, Lactobacillus Mycobacterium austroafricanum, Mycobacterium avium satsumensis, Lactobacillus secaliphilus, Lactobacillus (Battey disease/Lady Windermere syndrome), Mycobacte sharpeae, Lactobacillus Siliginis, Lactobacillus spicheri, rium avium paratuberculosis (implicated in Crohn's disease Lactobacillus Suebicus, Lactobacillus thailandensis, Lacto in humans and Johne's disease in sheep), Mycobacterium bacillus ultunensis, Lactobacillus vaccinostercus, Lactoba avium Silvaticum, Mycobacterium avium "hominissuis', cillus vaginalis, Lactobacillus versmoldensis, Lactobacillus Mycobacterium Colombiense, Mycobacterium boenickei, vini, Lactobacillus vitulinus, Lactobacillus zeae, Lactobacil 10 Mycobacterium bohemicum, Mycobacterium boiletii, Myco lus zymae, Leclercia species, Legionella species: Legionella bacterium botniense, Mycobacterium bovis (Bovine tubercu adelaidensis, Legionella anisa, Legionella beliardensis, losis), Mycobacterium branderi, Mycobacterium brisban Legionella birminghamensis, Legionella bOzemanii, ense, Mycobacterium brumae, Mycobacterium canariasense, Legionella brunensis, Legionella busanensis, Legionella Mycobacterium caprae, Mycobacterium cellatum, Mycobac cherrii, Legionella Cincinnatiensis, Legionella donaldsonii, 15 terium chelonae, Mycobacterium chimaera, Mycobacterium Legionella drancourti, Legionella drozanski, Legionella chitae, Mycobacterium chlorophenolicum, Mycobacterium erythra, Legionella fairfieldensis, Legionella fallonii, chubuense, Mycobacterium conceptionense, Mycobacterium Legionella feelei, Legionella geestiana, Legionella genomo confluentis, Mycobacterium conspicuum, Mycobacterium species, Legionella gratiana, Legionella gresilensis, cookii, Mycobacterium cosmeticum, Mycobacterium diern Legionella hackeliae, Legionella impletisoli, Legionella hoferi, Mycobacterium doricum, Mycobacterium du valii, israelensis, Legionella jamestowniensis, 'Candidatus Mycobacterium elephantis, Mycobacterium fallax, Myco Legionella jeonii, Legionella jordanis, Legionella lansin bacterium farcinogenes, Mycobacterium flavescens, Myco gensis, Legionella londiniensis, Legionella longbeachae, bacterium florentinum, Mycobacterium fluoroanthenivorans, Legionella lytica, Legionella maceachernii, Legionella Mycobacterium fortuitum, Mycobacterium fortuitum subsp. micdadei, Legionella moravica, Legionella nautarum, 25 Acetamidolyticum, Mycobacterium federiksbergense, Legionella Oakridgensis, Legionella parisiensis, Legionella Mycobacterium gadium, Mycobacterium gastri, Mycobacte pneumophila, Legionella quateirensis, Legionella quinliva rium genavense, Mycobacterium gilvium, Mycobacterium nii, Legionella rowbothamii, Legionella rubrilucens, goodi, Mycobacterium gordonae (Mycobacterium aquae), Legionella Sainthelensi, Legionella Santicrucis, Legionella Mycobacterium haemophilum, Mycobacterium hassiacum, Shakespearei, Legionella spiritensis, Legionella Steiger 30 Mycobacterium heckeshornense, Mycobacterium heidelber waltii, Legionella taurinensis, Legionella tucsonensis, gense, Mycobacterium hiberniae, Mycobacterium hodleri, Legionella wadsworthii, Legionella waltersii, Legionella Mycobacterium holsaticum, Mycobacterium houstonense, worsleiensis, Legionella yabuuchiae, Leminorella species, Mycobacterium immunogenium, Mycobacterium interjectum, Leptospira species: Leptospira interrogans, Leptospira kir Mycobacterium intermedium, Mycobacterium intracellulare, Schneri, Leptospira noguchii, Leptospira alexanderi, Lep 35 Mycobacterium kansasii, Mycobacterium komossense, to spira weilii, Leptospira genomospecies 1, Leptospira borg Mycobacterium kubicae, Mycobacterium kumamotonense, petersenii, Leptospira Santarosai, Leptospira inadai, Mycobacterium lacus, Mycobacterium lentiflavum, Myco Leptospira fainei, Leptospira broomii, Leptospira licerasiae, bacterium leprae (causes leprosy or Hansen disease/Hans Leptospira biflexia, Leptospira meyeri, Leptospira wolbachii, eniasis), Mycobacterium lepraemurium, Mycobacterium Leptospira genomospecies 3, Leptospira genomospecies 4, 40 madagascariense, Mycobacterium mageritense, Mycobacte Leptospira genomospecies 5; Lepromatous leprosy (Daniels rium malmoense, Mycobacterium marinum (Fish tank granu sen-Boeck disease), Leptospira canicola, Leptospira hebdo loma), Mycobacterium massiliense, Mycobacterium microti, madis, Leptospirosis (Weil disease/Leptospira icterohaemor Mycobacterium monacense, Mycobacterium montefiorense, rhagiae/Leptospira interrogans SOWa. Mycobacterium moriokaense, Mycobacterium mucogeni icterohaemorrhagiae), Leptotrichia, Leuconostoc species: 45 cum, Mycobacterium murale, Mycobacterium nebraskense, Leuconostoc carnosum, Leuconostoc citreum, Leuconostoc Mycobacterium neoaurum, Mycobacterium newOrleansense, durionis, Leuconostoc fallax, Leuconostocficulneum, Leu Mycobacterium nonchromogenicum, Mycobacterium novo conostoc fructosum, Leuconostoc garlicum, Leuconostoc castrense, Mycobacterium obuense, Mycobacterium palus gasicomitatum, Leuconostoc gelidum, Leuconostoc inhae, tre, Mycobacterium parafortuitum, Mycobacterium paras Leuconostoc kimchii, Leuconostoc lactis, Leuconostoc 50 crofulaceum, Mycobacterium parmense, Mycobacterium mesenteroides, Leuconostoc pseudoficulneum, Leuconostoc peregrinum, Mycobacterium phlei, Mycobacterium phocai pseudomesenteroides, Listeria species: Listeria grayi, List cum, Mycobacterium pinnipedii, Mycobacterium porcinum, eria innocua, Listeria ivanovii, Listeria monocytogenes Mycobacterium poriferae, Mycobacterium pseudoshottsii, (Listeriosis), Listeria Seeligeri, Listeria wellshimeri; Metha Mycobacterium pulveris, Mycobacterium psychrotolerans, nobacterium extroquens, Microbacterium multiforme, 55 Mycobacterium pyrenivorans, Mycobacterium rhodesiae, Micrococcus species: Micrococcus antarcticus, Micrococcus Mycobacterium Saskatchewanense, Mycobacterium scrofit flavus, Micrococcus luteus, Micrococcus lylae, Micrococcus laceum, Mycobacterium Senegalense, Mycobacterium Seou mucilaginosis, Micrococcus roseus, Micrococcus seden lense, Mycobacterium septicum, Mycobacterium Shimoidei, tarius, Mobiluncus, Moellerella species, Morganella species, Mycobacterium shottsii, Mycobacterium simiae, Mycobacte Moraxella species: Moraxella atlantae, Moraxella boevrei, 60 rium Smegmatis, Mycobacterium sphagni, Mycobacterium Moraxella bovis, Moraxella canis, Moraxella caprae, Szulgai, Mycobacterium terrae, Mycobacterium thermore Moraxella catarrhalis (Branhamella catarrhalis), Moraxella sistibile, Mycobacterium tokaiense, Mycobacterium triplex, caviae, Moraxella cuniculi, Moraxella equi, Moraxella lacu Mycobacterium triviale, Mycobacterium tuberculosis (major nata, Moraxella lincolnii, Moraxella nonliquefaciens, cause of human tuberculosis), Mycobacterium bovis, Myco Moraxella Oblonga, Moraxella Osloensis, Moraxella saccha 65 bacterium africanum, Mycobacterium canetti, Mycobacte rolytica, Morganella morganii, Mycobacterium species: rium caprae, Mycobacterium pinnipedii, Mycobacterium Mycobacterium abscessus, Mycobacterium africanum, tusciae, Mycobacterium ulcerans (causes Bairnsdale ulcer/ US 8,647,676 B2 39 40 Buruli ulcer), Mycobacterium vaccae, Mycobacterium van rata, Pseudomonas fulva, Pseudomonas monteilii, baalenii, Mycobacterium wolinskyi, Mycobacterium xenopi; Pseudomonas mosselii, Pseudomonas Oryzihabitans, Mycoplasma species: Mycoplasma fermentans, Mycoplasma Pseudomonas parafiulva, Pseudomonas plecoglossicida, genitalium, Mycoplasma hominis, Mycoplasma penetrans, Pseudomonas putida, Pseudomonas balearica, Pseudomo Mycoplasma phocacerebrale, Mycoplasma pneumoniae, nas luteola, Pseudomonas Stutzeri, Pseudomonas amygdale, Nanukayami (Seven-day fever/Gikiyami), Neisseria species: Pseudomonas avellanae, Pseudomonas Caricapapayae, Neisseria gonorrhoea (Gonococcus/Gonorrhea), Neisseria Pseudomonas cichorii, Pseudomonas coronafaciens, meningiditis (Meningococcus), Neisseria sicca, Neisseria Pseudomonas ficuserectae, Pseudomonas meliae, cinerea, Neisseria elongata, Neisseria flavescens, Neisseria Pseudomonas Savastanoi, Pseudomonas syringae, lactanica, Neisseria mucosa, Neisseria polysaccharea, Neis 10 Pseudomonas viridiflava, Pseudomonas abietaniphila, seria subflava, Nitrobacter species, Nocardia species: Pseudomonas acidophila, Pseudomonas agarici, Pseudomo Nocardia asteroides, Nocardia brasiliensis, Nocardia nas alcaliphila, Pseudomonas alkanolytica, Pseudomonas caviae; Noma (cancrum oriS/gangrenous stomatitis), Obe amyloderamosa, Pseudomonas asplenii, Pseudomonas azo sumbacterium, Oligotropha species, Orientia tsutsugamushi tifigens, Pseudomonas cannabina, Pseudomonas coenobios, (), Oxalobacter formigenes, Pantoea species: 15 Pseudomonas congelans, Pseudomonas costantinii, Pantoea agglomerans, Pantoea ananatis, Pantoea citrea, Pseudomonas cruciviae, Pseudomonas delhiensis, Pantoea dispersa, Pantoea punctata, Pantoea Stewartii, Pan Pseudomonas excibis, Pseudomonas extremorientalis, toea terrea, Pasteurella species: Pasteurella aerogenes, Pas Pseudomonas federiksbergensis, Pseudomonas fiscovagi teurella anatis, Pasteurella avium, Pasteurella bettvae, Pas nae, Pseudomonas gelidicola, Pseudomonas grimontii, teurella caballi, Pasteurella canis, Pasteurella dagmatis, Pseudomonas indica, Pseudomonas jessenii, Pseudomonas Pasteurella gallicida, Pasteurella gallinarum, Pasteurella injuensis, Pseudomonas kilomensis, Pseudomonas knack granulomatis, Pasteurella langaaensis, Pasteurella lymphan mussii, Pseudomonas koreensis, Pseudomonas lini, gitidis, Pasteurella mairii, Pasteurella multocida, Pasteurella Pseudomonas lutea, Pseudomonas moraviensis, Pseudomo pneumotropica, Pasteurella Skyensis, Pasteurella stomatis, nas Otitidis, Pseudomonas pachastrellae, Pseudomonas pal Pasteurella testudinis, Pasteurella trehalosi, Pasteurella tulla 25 leroniana, Pseudomonas papaveris, Pseudomonas peli, rensis, Pasteurella ureae, Pasteurella volantium, Pediococ Pseudomonas perolens, Pseudomonas poae, Pseudomonas cus species: Pediococcus acidilactici, Pediococcus cellicola, pohangensis, Pseudomonas psychrophila, Pseudomonas Pediococcus claussenii, Pediococcus damnosus, Pediococ psychrotolerans, Pseudomonas rathonis, Pseudomonas rep cus dextrinicus, Pediococcus ethanolidurans, Pediococcus tilivora, Pseudomonas resiniphila, Pseudomonas inopiniatus, Pediococcus parvulus, Pediococcuspentosaceus, 30 rhizosphaerae, Pseudomonas rubescens, Pseudomonas Pediococcus stilesii Peptostreptococcus species: Peptostrep Salomonii, Pseudomonas segitis, Pseudomonas septica, tococcus anaerobius, Peptostreptococcus asaccharolyticus, Pseudomonas simiae, Pseudomonas suis, Pseudomonas ther Peptostreptococcus harei, Peptostreptococcus hydrogenalis, motolerans, Pseudomonas tremae, Pseudomonas trivialis, Peptostreptococcus indoliticus, Peptostreptococcus ivorii, Pseudomonas turbinellae, Pseudomonas tuticorinensis, Peptostreptococcus lacrimalis, Peptostreptococcus lactolyti 35 Pseudomonas unsongensis, Pseudomonas vancouverensis, cus, Peptostreptococcus magnus, Peptostreptococcus micros, Pseudomonas Vranovensis, Pseudomonas xanthomarina, Peptostreptococcus Octavius, Peptostreptococcus previotii, Rahnella species, Ralstonia species: Ralstonia basilensis, Peptostreptococcus tetradius, Peptostreptococcus vaginalis, Ralstonia campinensis, Ralstonia eutropha, Ralstonia gilar Photorhabdus species, Photorhizobium species, Plesiomo dii, Ralstonia insidiosa, Ralstonia mannitolilytica, Ralstonia nas Shigelloides, Porphyromonas gingivalis, Pragia species, 40 metallidurans, Ralstonia paucula, Ralstonia pickettii, Ral Prevotella, Propionibacterium species: Propionibacterium stonia respiraculi, Ralstonia Solanacearum, Ralstonia syzy acnes, Propionibacterium propionicus, Proteus species: Pro gii, Ralstonia taiwanensis, Raoultella species, Rhodoblastus teus mirabilis, Proteus morganii, Proteus penneri, Proteus species, Rhodopseudomonas species, Rhinoscleroma, Rhizo rettgeri, Proteus vulgaris, Providencia species: Providencia bium radiobacter, Rhodococcus equi, Rickettsia species: friedericiana, Providencia Stuartii, Pseudomonas species: 45 Rickettsia africae, Rickettsia akari, Rickettsia australis, Rick Pseudomonas aeruginosa, Pseudomonas alcaligenes, ettsia Conorii, Rickettsia felis, Rickettsia japonica, Rickettsia Pseudomonas anguilliseptica, Pseudomonas argentinensis, mooseri, Rickettsia prowazekii (Typhus fever), Rickettsia Pseudomonas borbori, Pseudomonas citronellolis, rickettsii, Rickettsia Siberica, Rickettsia typhi, Rickettsia Pseudomonas flavescens, Pseudomonas mendocina, Conorii, Rickettsia africae, Rickettsia psittaci, Rickettsia Pseudomonas nitroreducens, Pseudomonas Oleovorans, 50 quintana, Rickettsia rickettsii, Rickettsia trachomae, Rothia Pseudomonas pseudoalcaligenes, Pseudomonas resino dentocariosa, Salmonella species: Salmonella arizonae, Sal vorans, Pseudomonas Straminea, Pseudomonas aurantiaca, monella Bongori, Salmonella enterica, Salmonella enteridi Pseudomonas aureofaciens, Pseudomonas chlororaphis, tis, Salmonella paratyphi, Salmonella typhi (Typhoid fever), Pseudomonas fragi, Pseudomonas lundensis, Pseudomonas Salmonella typhimurium, Salmonella Salamae, Salmonella taetrolens, Pseudomonas Antarctica, Pseudomonas azotofor 55 arizonae, Salmonella diarizonae, Salmonella houtenae, Sal mans, Pseudomonas brassicacearum, Pseudomonas bren monella indica, Samsonia species, Serratia species: Serratia neri, Pseudomonas Cedrina, Pseudomonas corrugate, entomophila, Serratia ficaria, Serratia fonticola, Serratia Pseudomonas fluorescens, Pseudomonas gessardii, grimesii, Serratia liquefaciens, Serratia marcescens, Serra Pseudomonas libanensis, Pseudomonas mandelii, tia Odoriferae, Serratia plvmuthica, Serratia proteamacu Pseudomonas marginalis, Pseudomonas mediterranea, 60 lans, Serratia quinivorans, Serratia rubidaea, Serratia ure Pseudomonas meridiana, Pseudomonas migulae, ilytica, Shewanella putrefaciens, Shigella boydii, Shigella Pseudomonas mucidolens, Pseudomonas Orientalis, dysenteriae, Shigella flexneri, Shigella sonnei, Sodalis spe Pseudomonas panacis, Pseudomonas proteolytica, cies, Spirillum species: Spirillum minus rat bite fever, Staphy Pseudomonas rhodesiae, Pseudomonas synxantha, lococcus species: Staphylococcus aureus, Staphylococcus Pseudomonas thivervalensis, Pseudomonas tolaasii, 65 auricularis, Staphylococcus capitis, Staphylococcus Caprae, Pseudomonas veronii, Pseudomonas denitrificans, Staphylococcus cohnii, Staphylococcus epidermidis, Staphy Pseudomonas pertucinogena, Pseudomonas Cremoricolo lococcus felis, Staphylococcus haemolyticus, Staphylococcus US 8,647,676 B2 41 42 hominis, Staphylococcus intermedius, Staphylococcus lug teria include but are not limited to meticillin-resistant S. dunensis, Staphylococcus pettenkoferi, Staphylococcus aureus, and multiresistant Paeruginosa, Klebsiella pneumo Saprophyticus, Staphylococcus Schleiferi, Staphylococcus niae and Acinetobacter. simulans, Staphylococcus vitulus, Staphylococcus warneri, Methicillin Resistant Staphylococcus aureus (MRSA) Staphylococcus xylosus, Stenotrophomonas species: The strain is resistant to all f-lactam antibiotics. The treat Stenotrophomonas acidaminiphila, Stenotrophomonas dok ment of MRSA is therefore difficult. The strain can cause both donensis, Stenotrophomonas koreensis, Stenotrophomonas local and systemic infections. maltophilia, Stenotrophomonas nitritireducens, Stenotroph Klebsiella pneumoniae, Multiresistant Clinical Isolate Omonas rhizophila, Streptobacillus species: Streptobacillus The strain has a plasmid-mediated, broad spectrum B-lac moniliformis (Streptobacillary rat bite fever); Streptococcus 10 tamase (Klebsiella Pneumoniae Carbapenemase (KPC) and species: Streptococcus Group A, Streptococcus Group B, is resistant to all clinical relevant B-lactam antibiotics. Fur thermore, it is in vitro resistant to many other non B-lactam Streptococcus agalactiae, Streptococcus aginosus, Strepto antibiotics. Infections with such microbes are difficult to treat coccus avium, Streptococcus bovis, Streptococcus canis, with available antibiotics. K. pneumoniae is a common cause Streptococcus Cricetus, Streptococcus faceium, Streptococ 15 of urinary tract infections, but can also cause systemic infec cus faecalis, Streptococcus ferus, Streptococcus gallinarum, tions. Streptococcus lactis, Streptococcus milleri, Streptococcus Pseudomonas aeruginosa, Multiresistant Clinical Isolate mition; Streptococcus mitis, Streptococcus mutans, Strepto P. aeruginosa is naturally resistant to a range of different coccus oralis, Streptococcus peroris, Streptococcus pneumo antibiotics, and the spectre of efficientagents is narrow. Addi niae, Streptococcus pyogenes, Streptococcus ratti, Strepto tionally, it has a high ability to develop resistance to new coccus salivarius, Streptococcus sanguinis, Streptococcus antibiotics. The actual strain is in vitro resistant to, or has sobrinus, Streptococcus parasanguinis, Streptococcus suis, reduced Susceptibility to antimicrobial agents commonly Streptococcus thermophilus, Streptococcus vestibularis, used in the treatment of P. aeruginosa infections. Severe Streptococcus viridans, Streptococcus uberis, Streptococcus infections with P aeruginosa occur with immune deficient ZOOepidemicus, Tatumella species, Trabulsiella species, Tre 25 patients and with weak, hospitalized patients. ponema species: Treponema carateum (Pinta), Treponema Acinetobacter, Multiresistant Clinical Isolate denticola, Treponema endemicum (Beel), Treponema palli Acinetobacter is naturally resistant to a range of different dum (Syphilis), Treponema pertenue (Yaws); Tropheryma antibiotics, and the spectre of efficient agents is narrow. With whipplei (Whipple disease), Tuberculoid leprosy, Urea one exception, the actual isolate in vitro resistant to, or have plasma urealyticum, Veillonella, Vibrio species: Vibrio aero 30 reduced Susceptibility to all antimicrobial agents used for genes, Vibrio aestuarianus, Vibrio agarivorans, Vibrio alben treatment of Acinetobacter infections. Severeinfections with sis, Vibrio alginolyticus, Vibrio brasiliensis, Vibrio calviensis, Acinetobacter occur with immune deficient patients and with Vibrio Campbellii, Vibrio chagasii, Vibrio cholerae (Cholera), weak, hospitalized patients. Vibrio cincinnatiensis, Vibrio Comma, Vibrio coralliilyticus, Fungi Vibrio crassostreae, Vibrio cyclitrophicus, Vibrio diabolicus, 35 In one embodiment the antimicrobial activity of the com Vibrio diazotrophicus, Vibrio ezurae, Vibrio fischeri, Vibrio position of the present invention is directed against a fungus, fluvialis, Vibriofortis, Vibrio furnissii, Vibrio gallicus, Vibrio i.e. it is an antifungal. Some examples of fungi include yeasts, gazogenes, Vibrio gigantis, Vibrio hallioticoli, Vibrio harveyi, molds and mushrooms. Vibrio hepatarius, Vibrio hispanicus, Vibrio ichthyoenteri, In one embodiment the antifungal activity is directed Vibrio kanaloae, Vibrio lentus, Vibrio litoralis, Vibrio logei, 40 against one or more pathogenic fungi selected from the group Vibrio mediterranei, Vibrio metschnikovii, Vibrio mimicus, consisting of, but not limited to Candida, , Cryp Vibrio mytili, Vibrio matriegens, Vibrio navarrensis, Vibrio tococcus, Histoplasma, Pneumocystis, Stachybotrys. neonatus, Vibrio neptunius, Vibrio nereis, Vibrio nigripul In one embodiment the antifungal activity is directed chritudo, Vibrio ordalii, Vibrio Orientalis, Vibrio pacinii, against one or more non-pathogenic fungi. Vibrio parahaemolyticus, Vibrio pectenicida, Vibrio penaei 45 In a preferred embodiment, the antifungal activity is cida, Vibrio pomeroyi, Vibrio ponticus, Vibrio proteolyticus, directed against a yeast, more preferred against Saccharomy Vibrio rotiferianus, Vibrio ruber, Vibrio rumoiensis, Vibrio ces cerevisiae. salmonicida, Vibrio scophthalmi, Vibrio splendidus, Vibrio In another preferred embodiment the antifungal activity is superstes, Vibrio tapetis, Vibrio tasmaniensis, Vibrio tubi directed against a mold, more preferred against Aspergillus ashii, Vibrio vulnificus, Vibrio wodanis, Vibrioxuii, Vogesella 50 niger: indigofera, Wigglesworthia species, Wolbachia species, In one embodiment, the antifungal activity is not directed Xenorhabdus species, Yersinia enterocolitica, Yersinia pestis, against Candida albicans. Yersinia pseudotuberculosis, and Yokenella species. Virus In a preferred embodiment, the antibacterial activity is In one embodiment the present invention relates to treat directed against one or more pathogenic bacteria. More pre 55 ment of one or more diseases caused by one or more vira Such ferred, the antibacterial activity is directed against the bacte as one or more vira selected from the group consisting of ria selected from the group comprising Pseudomonas, Abelson murine leukemia virus (Ab-MLV. A-MuV), acute Enterococcus, Listeria, Bacillus, Staphylococcus, Escheri laryngotracheobronchitis virus (or HPIV), Adelaide River chia, Salmonella and Clostridium. In an even more preferred virus, Adeno-associated virus group (Dependevirus), Aden embodiment the bacteria are selected from the group com 60 ovirus, African horse sickness virus, African Swine fever prising Pseudomonas aeruginosa, Enterococcus faecalis, virus, AIDS virus, Aleutian mink disease, parvovirus, alfalfa Listeria monocytogenes, Bacillus cereus, Staphylococcus mosaic virus, Alphaherpesvirinae (including HSV 1 and 2 aureus, Escherichia coli, Salmonella berta, Clostridium per and varicella), Alpharetrovirus (Avian leukosis virus, Rous fringens and Clostridium bifermentans. sarcoma virus), Alphavirus, alkhurma virus, ALV related In another embodiment the antibacterial activity is directed 65 virus, Amapari virus, Andean potato mottle virus, Aphthovi against on or more bacteria resistant to one or more conven rus, Aquareovirus, arbovirus, arbovirus C. arbovirus group A, tional antibiotics. Examples of resistant or multiresistant bac arbovirus group B, Arenavirus group, Argentine hemorrhagic US 8,647,676 B2 43 44 fever virus, Argentinian hemorrhagic fever virus, Arterivirus, Entomopoxyirinae, Entomopoxvirus A, Entomopoxvirus B, Astrovirus, Ateline herpesvirus group, Aujezky's disease Entomopoxvirus C, enzyme elevating virus, epidemic hem virus, Aura virus, Ausduk disease virus, Australian bat lys orrhagic fever virus, epizootic hemorrhagic disease virus, savirus, Aviadenovirus, avian erythroblastosis virus, avian Epsilonretrovirus, Epstein-Barr virus (EBV: Human herpes infectious bronchitis virus, avian leukemia virus, Avian leu virus 4 HHV-4), equid alphaherpesvirus 1, equid alphaherp kosis virus (ALV), avian lymphomatosis virus, avian myelo esvirus 4, equid herpesvirus 2, equine abortion virus, equine blastosis virus, avian paramyxovirus, avian pneumoencepha arteritis virus, equine encephalosis virus, equine infectious litis virus, avian reticuloendotheliosis virus, avian sarcoma anemia virus, equine morbillivirus, equine rhinopneumonitis virus, avian type C retrovirus group, Avihepadnavirus, Avi virus, equine rhinovirus, Eubenangu virus, European elk pap poxvirus, B virus (Cercopithecine herpesvirus 1), B19 virus 10 illomavirus, European Swine fever virus, Everglades virus, (Parvovirus B19), Babanki virus, baboon herpesvirus, bacte Eyach virus, Fabavirus, felid herpesvirus 1, feline calicivirus, rial virus, baculovirus, barley yellow dwarf virus, Barmah feline fibrosarcoma virus, feline herpesvirus, feline immuno Forest virus, bean pod mottle virus, bean rugose mosaic virus, deficiency virus, feline infectious peritonitis virus, feline leu Bebaru virus, Berrimah virus, Betaherpesvirinae, betaretro kemia/sarcoma virus, feline leukemia virus, feline panleuko virus, Bird flu, Birnavirus, Bittner virus, BK virus, Black 15 penia virus, feline parvovirus, feline sarcoma virus, feline Creek Canal virus, bluetongue virus, Bolivian hemorrhagic syncytial virus, Fijivirus, Filovirus, Flanders virus, Flavivi fever virus, Bomadisease virus, border disease of sheep virus, rus, foot and mouth disease virus, Fort Morgan virus, Four borna virus, bovine alphaherpesvirus 1, bovine alphaherpes Cornershantavirus, fowladenovirus 1, Fowlpox virus, Friend virus 2, bovine coronavirus, bovine ephemeral fever virus, virus, Furovirus, Gammaherpesvirinae, gammaretrovirus, bovine immunodeficiency virus, bovine leukemia virus, GB virus C (GBV-C; formerly Hepatitis G virus), Geminivi bovine leukosis virus, bovine mammillitis virus, bovine pap rus, German measles virus, Getah virus, gibbon ape leukemia illomavirus, bovine papular stomatitis virus, bovine parvovi virus, green monkey virus (mullburg), glandular fever virus, rus, bovine syncytial virus, bovine type Concovirus, bovine goatpox virus, golden shinner virus, Gonometa virus, goose viral diarrhea virus, bracovirus, broad bean mottle virus, parvovirus, granulosis virus, Gross virus, ground Squirrel broad bean stain virus, brome mosaic virus, Bromovirus, 25 hepatitis B virus, group A arbovirus, Guanarito virus, guinea Buggy Creek virus, bullet shaped virus group, Bunyamwera pig cytomegalovirus, guinea pig type C virus, Hantavirus, virus, Bunyavirus, Burkitt's lymphoma virus, Bwamba hard clam reovirus, hare fibroma virus, HCMV (human Fever, Bwattany hetero virus, CA virus (Croup-associated cytomegalovirus), helper virus, hemadsorption virus 2, virus/parainfluenza vius type 2), Calicivirus, California hemagglutinating virus of Japan, hemorrhagic fever virus, encephalitis virus, camelpox virus, canarypox virus, canid 30 Hendra virus, Henipaviruses, Hepadnavirus, hepatitis A herpesvirus, canine coronavirus, canine distemper virus, virus, hepatitis B virus, hepatitis C virus, hepatitis D (delta) canine herpesvirus, canine minute virus, canine parvovirus, virus, hepatitis E virus, hepatitis F virus, hepatitis G virus, Cano Delgadito virus, Capillovirus, caprine arthritis virus, hepatitis nonA nonB virus, hepatoencephalomyelitis reovirus caprine encephalitis virus, Caprine Herpes Virus, Capripox 3, Hepatovirus, heron hepatitis B virus, herpes B virus, Her virus, Cardiovirus, Carlavirus, Carmovirus, carrot mottle 35 pes simplex virus, herpes simplex virus 1, herpes simplex virus, Cassia yellow blotch virus, Caulimovirus, Cauliflower virus 2, Herpesvirus, Herpes Zoster, Herpes virus 6. Herpes mosaic virus, caviid herpesvirus 1, Cercopithecine herpesvi virus 7. Herpes virus 8, Herpesvirus ateles, Herpesvirus rus 1, Cercopithecine herpesvirus 2, cereal yellow dwarf hominis, Herpesvirus Saimiri, Herpesvirus Suis, Herpesvirus virus, Chandipura virus, Changuinola virus, channel catfish varicellae, Highlands J virus, Hirame rhabdovirus, HIV-1, virus, Charleville virus, chickenpox virus, Chikungunya 40 hog cholera virus, Hordeivirus, Horse Flu, HTLV-1, HTLV-2, virus, chimpanzee herpesvirus, Chordopoxyirinae, chub human adenovirus 2, human alphaherpesvirus 1, human reovirus, chum salmon virus, Closterovirus, Cocal virus, alphaherpesvirus 2, human alphaherpesvirus 3, human B Coho Salmon reovirus, coital exanthema virus, Colorado tick lymphotropic virus, human betaherpesvirus 5, human coro fever virus, Coltivirus Columbia SK virus, Commelina yel navirus, Human enterovirus A, Human enterovirus B. Human low mottle virus, Common cold virus, Comovirus, Condylo 45 Flu, human foamy virus, humangammaherpesvirus 4., human mata accuminata, congenital cytomegalovirus, contagious gammaherpesvirus 6, human hepatitis. A virus, human herp eethyma virus, contagious pustular dermatitis virus, Coro esvirus 1 group, human herpesvirus 2 group, human herpes navirus, Corriparta virus, coryza virus, cowpea chlorotic virus 3 group, human herpesvirus 4 group, human herpesvi mottle virus, cowpea mosaic virus, cowpea virus, cowpox rus 6, human herpesvirus 8, human immunodeficiency virus virus, coxsackie virus, CPV (cytoplasmic polyhedrosis 50 (HIV), human immunodeficiency virus 1, human immunode virus), cricket paralysis virus, Crimean-Congo hemorrhagic ficiency virus 2, Human metapneumovirus, human papillo fever virus, croup associated virus, Crypotovirus, Cucumovi mavirus, human T cell leukemia virus, human T cell leukemia rus, Cypovirus, Cytomegalovirus (HCMV or Human Herp virus I, human T cell leukemia virus II, human T cell leukemia esvirus 5 HHV-5), cytoplasmic polyhedrosis virus, Cytorhab virus III, human T cell lymphoma virus I, human T cell dovirus, deer papillomavirus, Deltaretrovirus (Human 55 lymphoma virus II, human T cell lymphotropic virus type 1, T-lymphotropic virus), Deformed wing virus DWV. Dengue, human T cell lymphotropic virus type 2, human T lympho Densovirus, Dependovirus, Dhori virus, Dianthovirus, dip tropic virus I, human T lymphotropic virus II, human T lym lorna virus, DNA virus, Dobrava-Belgrade Virus, Dog Flu, photropic virus III, ichnovirus, larvirus, infantile gastroen Drosophila C virus, duck hepatitis B virus, duck hepatitis teritis virus, infectious bovine rhinotracheitis virus, virus 1, duck hepatitis virus 2, duovirus, Duvenhage virus, 60 infectious haematopoietic necrosis virus, infectious pancre eastern equine encephalitis virus, eastern equine encephalo atic necrosis virus, influenza virus, influenzavirus A, influen myelitis virus, Ebola virus, Ebola-like virus, Echovirus, Zavirus B, influenzavirus C, influenzavirus D, influenzavirus echovirus 10, echovirus 28, echovirus 9, ectromelia virus, pr8, insect iridescent virus, insect virus, interfering virus, EEE virus (Eastern equine encephalitis virus), EIA virus iridovirus, Isavirus, Japanese B virus, Japanese encephalitis (equine infectious anemia), EMC virus (Encephalomyocardi 65 virus, JC virus, Junin virus, Johnson grass mosaic virus, tis), Emiliania huxleyi virus 86, encephalitis virus, encepha Kaposi's sarcoma-associated herpesvirus, Kemerovo virus, lomyocarditis virus, Endogenous retrovirus, Enterovirus, Kilham's rat virus, Klamath virus, Kolongo virus, Korean US 8,647,676 B2 45 46 hemorrhagic fever virus, kumba virus, Kumlinge virus, Kun myelitis virus, porcine parvovirus, porcine transmissible gas jin virus, Kyasanur forest disease, Kyzylagach virus, La troenteritis virus, porcine type C virus, Potato leaf roll virus, Crosse virus, lactic dehydrogenase elevating virus, Lagos bat Potato mop top virus, Potato virus Y. Potexvirus, Potyvirus, virus, Lambda phage, langat virus, Langur virus, lapine par Powassan encephalitis virus, Poxvirus, poxvirus variolae, vovirus, Lassa fever virus, Lassa virus, latent rat virus, LCM Prospect Hill virus, provirus, pseudocowpox virus, pseudo virus, Leaky virus, Lentivirus, Leporipoxvirus, leukemia rabies virus, psittacinepox virus, Puumala virus, Qalyub virus, leukovirus, louping ill virus, lumpy skin disease virus, virus, Quail pea mosaic virus, quailpox virus, Queensland Luteovirus, lymphadenopathy associated virus, Lymphocytic fruitfly virus, Quokkapox virus, rabbit fibroma virus, rabbit choriomeningitis virus (LCMV), Lymphocryptovirus, lym kidney Vaculolating virus, rabbit papillomavirus, Rabies phocytic choriomeningitis virus, lymphoproliferative virus 10 virus, raccoon parvovirus, raccoonpox virus, radish mosaic group, Lyssavirus, Machupo virus, mad itch virus, maize virus, Ranikhet virus, rat cytomegalovirus, rat parvovirus, rat chlorotic dwarf virus, maize rough dwarf virus, mammalian virus, Rauscher's virus, recombinant vaccinia virus, recom type B oncovirus group, mammalian type B retroviruses, binant virus, Red Clover Necrotic Mosaic Virus, reovirus, mammalian type C retrovirus group, mammalian type D ret reovirus 1, reovirus 2, reovirus 3, reptilian type C virus, roviruses, mammary tumor virus, Mapuera virus, Marafivi 15 Respiratory syncytial virus, respiratory virus, reticuloendot rus, Marburg virus, Marburg-like virus, Mason Pfizer mon heliosis virus, Retrovirus, Rhabdovirus, Rhabdovirus carpia, key virus, Mastadenovirus, Mayaro virus, ME virus, Measles Rhadinovirus, Rhinovirus, Rhizidiovirus, rice dwarf virus, virus, Melandrium yellow fleck virus, Menangle virus, rice gall dwarf virus, rice hoja blanca virus, rice ragged stunt Mengo virus, Mengovirus, Merkel cell polyomavirus, Mid virus, Rift Valley fever virus, Riley's virus, rinderpest virus, delburg virus, milkers nodule virus, mink enteritis virus, RNA tumor virus, RNA virus, Roseolovirus, Ross River minute virus of mice, MLV related virus, MM virus, Mokola virus, Rotavirus, rougeole virus, Rous sarcomavirus, Rubella virus, Molluscipoxvirus, Molluscum contagiosum virus, virus, rubeola virus, Rubivirus, Russian autumn encephalitis Moloney murine leukemia virus (M-MuDV), monkey B virus, S6-14-03 virus, SA 11 simian virus, SA 15, SA2 virus, virus, Monkeypox virus, Mononegavirales, Morbillivirus, SA6 virus, SA8 virus, Sabia virus, Sabio virus, Sabo virus, Mount Elgon bat virus, mouse cytomegalovirus, mouse 25 Saboya virus, Sabulodes caberata GV, Sacbrood virus, Sac encephalomyelitis virus, mouse hepatitis virus, mouse K charomyces cerevisiae virus L-A, Saccharomyces cerevisiae virus, mouse leukemia virus, mouse mammary tumor virus, virus La, Saccharomyces cerevisiae virus LBC, Sagiyama mouse minute virus, mouse pneumonia virus, mouse polio virus, Saguaro cactus virus, Saimirine herpesvirus 1. myelitis virus, mouse polyomavirus, mouse sarcoma virus, Saimiriine herpesvirus 2, Sainpaulia leaf necrosis virus, mousepox virus, Mozambique virus. Mucambo virus, 30 SaintAbb’s Head virus, Saint-Floris virus, Sakhalin virus, Sal mucosal disease virus, Mumps virus, murid betaherpesvirus Vieja virus, Salanga virus, Salangapox virus, Salehabad 1, murid cytomegalovirus 2, murine cytomegalovirus group, virus, salivary gland virus, Salmonid herpesvirus 1, Salmonid murine encephalomyelitis virus, murine hepatitis virus, herpesvirus 2, Salmonis virus, Sambucus vein clearing virus, murine leukemia virus, murine nodule inducing virus, murine Samia cynthia NPV. Samia pryeri NPV. Samia ricini NPV. polyomavirus, murine sarcoma virus, Muromegalovirus, 35 Sammons' Opuntia virus, SanAngelo virus, San Juan virus, Murray Valley encephalitis virus, myxoma virus, Myxovirus, San Miguel sealion virus, San Perlita virus, Sand rat nuclear Myxovirus multiforme, Myxovirus parotitidis, Nairobi sheep inclusion agents, Sandfly fever Naples virus, Sandfly fever disease virus, Nairovirus, Nanirnavirus, Narivavirus, Ndumo Sicilian virus, Sandjimba virus, Sango virus, Santa Rosa virus, Necrovirus, Neethling virus, Nelson Bay virus, Nem virus, Santarem virus, Santosai temperate virus, Sapphire II tickVirus, Nepovirus, neurotropic virus, New World Arenavi 40 virus, Sapporo-like virus, Saraca virus, Sarracenia purpurea rus, newborn pneumonitis virus, Newcastle disease virus, virus, SARS virus, satellite virus, Sathuperi virus, Satsuma Nipah virus, noncytopathogenic virus, Norovirus, Norwalk dwarf virus, Saturnia pavonia virus, Saturnia pyri NPV. Sau virus, nuclear polyhedrosis virus (NPV), nipple neck virus, marez Reef virus, Sawgrass virus, Sceliodes cordalis NPV. Onyongnyong virus, oat sterile dwarf virus, Ockelbo virus, Schefflera ringspot virus, Sciaphila duplex GV. Scirpophaga Omsk hemorrhagic fever virus, oncogenic virus, oncogenic 45 incertulas NPV. Sciurid herpesvirus, Sciurid herpesvirus 2, viruslike particle, oncornavirus, Orbivirus, Orf virus, Scoliopteryx libatrix NPV. Scopelodes contracta NPV. Oropouche virus, Orthohepadnavirus, orthomyxovirus, Scopelodes venosa NPV. Scopula subpunctaria NPV. Scoto Orthopoxvirus, Orthoreovirus, Orungo, ovine papillomavi gramma trifolii GV, Scotogramma trifolu NPV. Scrophularia rus, ovine catarrhal fever virus, owl monkey herpesvirus, mottle virus, SDAV (sialodacryoadenitis virus), sealpox Palyam virus, Papillomavirus, Papillomavirus Sylvilagi, 50 virus, Selenephera lunigera NPV. Selepa celtis GV, Seletar Papovavirus, Parainfluenza virus human (HPIV), parainflu virus, Selidosema Suavis NPV, Semidonta biloba NPV. enza virus type 1 human (HPIV-1), parainfluenza virus type 2 Semiothisa sexmaculata GV, Semliki Forest Virus, Sena human (HPIV-2), parainfluenza virus type 3 human (HPIV Madureira virus, Sendai virus, SENV-D, SENV-H, Seoul 3), parainfluenza virus type 4 human (HPIV-4), Paramyxovii virus, Sepik virus, Serra do Navio virus, Serrano golden rus, Parapoxvirus, paravaccinia virus, parsnip yellow fleck 55 mosaic virus, Sesame yellow mosaic virus, Sesamia calam virus, Parvovirus, Parvovirus B19, pea enation mosaic virus, istis NPV. Sesamia Cretica GV, Sesamia inferens NPV. Sesa Pestivirus, Phlebovirus, phocine distemper virus, Phytoreovi mia nonagrioides GV, Setora nitens virus, Shallot latent rus, Picodnavirus, Picornavirus, pig cytomegalovirus, virus, Shamonda virus, Shark River virus, Sheep associated pigeonpox virus, Piry virus, Pixuna virus, plant rhabdovirus malignant catarrhal fever, Sheep papillomavirus, Sheep pull group, plant virus, pneumonia virus of mice, Pneumovirus, 60 monary adenomatosis associated herpesvirus, sheeppoX Poliomyelitis virus, Poliovirus, Polydnavirus, polyhedral virus, Shiant Islands virus, Shokwe virus, Shope fibroma virus, Polyoma virus, Polyomavirus, Polyomavirus bovis, virus, Shope papilloma virus, Shuni virus, Siamese cobra Polyomavirus cercopitheci, Polyomavirus hominis 2, Polyo herpesvirus, Sibine fusca densovirus, Sida golden mosaic mavirus maccacae 1, Polyomavirus muris 1, Polyomavirus virus (SiGMV), Sida golden yellow vein virus (SiGYVV), muris 2, Polyomavirus papionis 1, Polyomavirus papionis 2. 65 Sigma virus, Sikte water-borne virus, Silverwater virus, Polyomavirus Sylvilagi, Pongine herpesvirus 1, porcine epi Simbu virus, Simian adenoviruses 1 to 27, Simian agent virus demic diarrhea virus, porcine hemagglutinating encephalo 12, Simian enterovirus 1 to 18, simian foamy virus, Simian US 8,647,676 B2 47 48 hemorrhagic fever virus, simian hepatitis A virus, simian potato feathery mottle virus, Sweet potato internal cork virus, human immunodeficiency virus, simian immunodeficiency Sweet potato latent virus, Sweet potato mild mottle virus, virus, simian parainfluenza virus, Simian rotavirus SA11. Sweet potato russet crack virus, Sweet potato vein mosaic Simian sarcoma virus, simian T cell lymphotrophic virus, virus, Sweet potato yellow dwarf virus, Sweetwater Branch Simian type D virus 1, Simian Vancella herpesvirus, simian 5 virus, Swine cytomegalovirus, Swine Flu, Swine infertility virus, simian virus 40, Simplexvirus, Simulium vittatum and respiratory syndrome virus, Swinepox virus, Swiss densovirus, Sin Nombre virus, Sindbis virus, Sintlems mouse leukemia virus, Sword bean distortion mosaic virus, onion latent virus, Sixgun city virus, Skunkpox virus, Small Synaxis jubararia NPV. Synaxis pallulata NPV. Synetaeris pox virus, Smelt reovirus, Smerinthus ocellata NPV. Smithi tenuifemur virus, Syngrapha selecta NPV. T4 phage, T7 antha virus, Snakehead rhabdovirus, Snowshoe hare virus, 10 phage, TAC virus, Tacaiuma virus, Tacaribe complex virus, Snyder-Theilen feline sarcoma virus, Sobemovirus, Sofyn Tacaribe virus, Tadpole edema virus LT 1-4, Taggert virus, virus, Soil-borne wheat mosaic virus, Sokoluk virus, Tahyna virus, Tai virus, TaiasSui virus, Tamana bat virus, Solanum apical leaf curl virus, Solanum modiflorum mottle Tamarillo mosaic virus, Tamdy virus, Tamiami virus, virus, Solanurn yellows virus, Soldado virus. Somerville Tanapox virus, Tanga virus, Tanjong Rabok virus, Taro bacil virus 4, Sonchus mottle virus, Sonchus virus, Sonchus yellow 15 liform virus, Badnavirus Tataguine virus, Taterapox virus, net virus, Sorghum chlorotic spot virus, Sorghum mosaic Taterapox virus, Teasel mosaic virus, Tehran virus, Telfairia virus, Sorghum virus, Sororoca virus, Soursop yellow blotch mosaic virus, Telok Forest virus, Tembe virus, Tembusu virus, South African passiflora virus, South American hem virus, Tench reovirus, Tensaw virus, Tenvivirus, Tephrosia orrhagic fever viruses, South African passiflora virus, South symptomless virus, Termeil virus, Tete virus, Tetralopha River virus, Southern bean mosaic virus, Southern potato scortealis NPV. Tetropium cinnamoptemm NPV. Texas pep latent virus, Sowbane mosaic virus, Sowthistle yellow vein per virus, Thailand virus, Thaumetopoea pityocampa virus, virus, Soybean chlorotic mottle virus, Soybean crinkle leaf Theiler’s encephalomyelitis virus. Theiler's virus. Theophila virus, Soybean dwarf virus, Soybean mosaic virus, SPAr mandarina NPV. Theretra japonica NPV. Thermoproteus 2317 virus, Sparganothis pettitana NPV, sparrowpox virus, virus 1, Thermoproteus virus 2, Thermoproteus virus 3, Ther Spartina mottle virus, Spectacled caimanpox virus, SPH 25 moproteus virus 4. Thiafora virus. Thimiri virus. Thistle 114202 virus, Sphenicid herpesvirus 1, Sphinx ligustri NPV. mottle virus, Thogoto virus, Thormodseyjarklettur virus, Spider monkey herpesvirus, Spilarctia subcarnea NPV. Spi Thosea asignavirus, Thosea baibarana NPV. Thosea sinensis lonota ocellana NPV. Spilosoma lubricipeda NPV. Spinach GV. Thottapalayam virus, Thylidolpteryx ephemeraeformis latent virus, Spinach temperate virus, Spiroplasma phage 1, NPV. Thymelicus lineola NPV. Tilbrogargan virus, Ticera cas Spiroplasma phage 4, Spiroplasma phage aa, Spiroplasma 30 tanea NPV. Tick borne encephalitis virus (TBEV)—Euro phage C1/T52, Spodoptera exempta cypovirus, Spodoptera pean and Far Eastern subtypes, Tillamook virus, Tilligerry exigua virus, Spodoptera frugiperda virus, Spodoptera lati virus, Timbo virus, Tilmboteua virus, Tilmaroo virus, Tind fascia virus, Spodoptera littoralis, Spodoptera mauritia holmur virus, Tinea pellionella NPV. Tineola hisselliella virus, Spodoptera Ornithogalli virus, Spondweni virus, NPV. Tinpula paludosa NPV. Timracola plagiata NPV. spring beauty latent virus, Spring viremia of carp virus, Spu 35 Tioman virus, Tlacotalpan virus, Tobacco bushy top virus, mavirus (SFV. HFV), Squash leaf curl virus, squash mosaic Tobacco etch virus, Tobacco leaf curl virus, Tobacco mild virus, squirrel fibroma virus, Squirrel monkey herpesvirus, green mosaic virus, tobacco mosaic virus, Tobacco mosaic squirrel monkey retrovirus, SR-11 virus, Sri Lankan passion virus satellite, Tobacco mottle virus, Tobacco necrosis virus, fruit mottle virus, Sripur virus, SSV 1 virus group, StAbbs Tobacco necrosis virus satellite, Tobacco necrosis virus Small Head virus, St. Louis encephalitis virus, Staphylococcus 40 satellite, Tobacco necrotic dwarf virus, tobacco rattle virus, phage 107, Staphylococcus phage 187, Staphylococcus Tobacco ringspot virus, Tobacco streak virus, Tobacco stunt phage 2848A, Staphylococcus phage 3A, Staphylococcus virus, Tobacco vein banding mosaic virus, Tobacco vein dis phage 44A HJD, Staphylococcus phage 77, Staphylococcus torting virus Tobacco vein mottling virus, Tobacco wilt virus, phage B11-M15, Staphylococcus phage Twort, Starlingpox Tobacco yellow dwarf virus, Tobacco yellow net virus, virus, Statice virus Y. P. STLV (simian T lymphotropic virus) 45 Tobacco yellow vein virus, Tobamovirus Tobravirus, Togavi type I, STLV (simian T lymphotropic virus) type II, STLV rus, Tomato apical stunt Viroid, Tomato aspermy virus, (simian T lymphotropic virus) type III, stomatitis papulosa Tomato black ring virus, Tomato black ring virus satellite, virus, Stratford virus, Strawberry crinkle virus, Strawberry Tomato bunchy top viroid, tomato bushy stunt Virus, Tomato latent ringspot virus, Strawberry mild yellow edge virus, bushy stunt virus satellite, Tomato golden mosaic virus, Strawberry vein banding virus, Streptococcus phage 182, 50 Tomato leaf crumple virus, Tomato leaf curl virus, Tomato Streptococcus phage 2BV. Streptococcus phage A25, Strep leafroll virus, Tomato mosaic virus, Tomato mottle virus, tococcus phage 24, Streptococcus phage PE1, Streptococcus Tomato pale chlorosis virus, Tomato planta macho Viroid, phage VD13, Streptococcus phage fD8, Streptococcus phage Tomato pseudo-curly top virus, Tomato ringspot virus, CP-1, Streptococcus phage Cvir, Streptococcus phage H39, Tomato spotted wilt virus, Tomato top necrosis virus, Tomato Strigid herpesvirus 1, Striped bass reovirus, Striped Jack 55 vein yellowing virus, Tomato yellow dwarf virus, Tomato nervous, necrosis virus, Stump-tailed macaque virus, Sub yellow leaf curl virus, Tomato yellow mosaic virus, Tomato maxillary virus, Subterranean clover mottle virus, Subterra yellow top virus, Tombusvirus, Tongan vanilla virus, Torovi nean clover mottle virus satellite, Subterranean cloverred leaf rus, Torque teno virus, Tortrix loeflingiana NPV. Tortrix viri virus, Subterranean clover stunt virus, Sugarcane bacilliform dana NPV. Toscana virus, Tospovirus, Toxorhynchites brevi virus, Sugarcane mild mosaic virus, Sugarcane mosaic virus, 60 palpis NPV. Trabala vishnou NPV. Tradescantia/Zebrina Sugarcane streak virus, Suid alphaherpesvirus 1, Suid herpes virus, Trager duck spleen necrosis virus, Tranosema sp. virus 2, Suipoxvirus, Sulfolobus virus 1, Sunday Canyon Virus, transforming virus, Tree shrew adenovirus 1, Tree virus, Sunflower crinkle virus, Sunflower mosaic virus, Sun shrew herpesvims, Triatoma virus, Tribec virus, Trichiocam flower rugose mosaic virus, Sunflower yellow blotch virus, pus irregularis NPV. Trichiocampus viminalis NPV. Tri Sunflower yellow ringspot virus, Sun-hemp mosaic virus, 65 chomonas vaginalis virus, Trichoplusia ni cypovirus 5, Tri swamp fever virus, Sweet clover necrotic mosaic virus, Sweet choplusia ni granulovirus, Trichoplusia ni MNPV. potato A virus, Sweet potato chlorotic leafspot virus, Sweet Trichoplusia ni Single SNPV. Trichoplusia ni virus, Tricho US 8,647,676 B2 49 50 Santhes mottle virus, Triticum aestivum chlorotic spot virus, XP5, Xenopus virus T21, Xiburema virus, Xingu virus, Trivittatus virus, Trombetas virus, Tropaeolum virus 1, Tro Xylena curvimacula NPV.Y73 sarcoma virus, Yaba monkey paeolum virus 2, Trubanarnan virus, Tsuruse virus, Tucun tumor virus, Yaba-1 virus, Yaba-7 virus, Yacaaba virus, Yam duba virus, Tulare apple mosaic virus, Tulip band breaking mosaic virus, Yaounde virus, Yaquina Head virus, Yatapoxvi virus, Tulip breaking virus, Tulip chlorotic blotch virus, Tulip rus, Yellow fever virus, Yogue virus, Yokapox virus, Yokase top breaking virus, Tulip virus X, tumor virus, Tupaia virus, virus, Yponomeuta cognatella NPV, Yponomeuta evonymella Tupaiid herpesvirus 1, Turbot herpesvirus, Turbot reovirus, NPV. Yponomeuta malinellus NPV, Yponomeuta padella Turkey adenoviruses 1 to 3, Turkey coronavirus, Turkey her NPV, Yucca baciliform virus, Yug Bogdanovac virus, Zaliv pesvirus 1, turkey rhinotracheitis virus, turkeypox virus, Tur Terpeniya virus, Zea mays virus, Zegla virus, Zeiraphera lock virus, Turnip crinkle virus, Turnip crinkle virus satellite, 10 Turnip mild yellows virus, Turnip mosaic virus, Turnip diniana virus, Zeiraphera pseudotsugana NPV. Zika virus, rosette virus, turnip yellow mosaic virus, Turuna virus, Zirqa virus, Zoysia mosaic virus, Zucchiniyellow fleck virus, Tymovirus, Tyuleniy virus, type C retroviruses, type D Zucchini yellow mosaic virus, and Zygocactus virus. oncovirus, type D retrovirus group, Uasin Gishu disease Microbial Infections virus, Uganda S virus, Ugymyia sericariae NPV. ulcerative 15 In one embodiment the present invention relates to treat disease rhabdovirus, Ullucus mild mottle virus, Ullucus ment of one or more microbial infectious diseases by admin mosaic virus, Ullucus virus C, Umatilla virus, Umbre virus, istration of the composition according to the present inven Una virus. Upolu virus, UR2 sarcoma virus, Uranotaenia tion to an individual in need thereof. The infectious disease Sapphirina NPV. Urbanus proteus NPV. Urucuri virus, Usti can be any type of infection including the types of infections lago maydis virus 1, Ustilago maydis virus 4, Ustilago maydis mentioned elsewhere herein and those listed in Tables 1, 2, 3, virus 6. Usutu virus, Uting a virus, Utive virus, Uukuniemi or 4 herein below. virus group, Vaccinia virus, Vaeroy virus, Vallota mosaic virus, Vanessa atalanta NPV, Vanessa cardui NPV. Vanessa TABLE 1 prorsa NPV. Vanilla mosaic virus, Vanilla necrosis virus, Human diseases caused by bacteria Varicella Zoster virus, Varicellovirus, Varicola virus, variola 25 major virus, variola virus, Vasin Gishu disease virus, Vellore Disease Casual Agent virus, Velvet tobacco mottle virus, Velvet tobacco mottle Strep Throat, Scarlet Fever Streptococcus, Pyogenes virus satellite, Venezuelan equine encephalitis virus, Venezu Diphtheria Corynebacterium diphtheriae elan equine encephalomyelitis virus, Venezuelan hemor Pertussis (Whooping bordeteila pertissis rhagic fever virus, Vesicular stomatitis virus, Vesiculovirus, 30 Cough) Meningococcal Vibrio phage 06N-22P, Vibrio phage 06N-58P, Vibrio phage 4996, Vibriophagea3a, Vibriophage I, Vibriophage II, Vibrio Flavobacterium meningitis Flavobacterium meningospecticum phage m, Vibrio phage IV, Vibrio phage kappa, Vibrio phage Tuberculosis Mycobacterium tuberculosis int-1, Vibrio phage OXN-52P, Vibrio phage OXN-IOOP, Pneumococcal pneumonia Steptococcits pneumoniae Vibrio phage v6, Vibrio phage Vfl2, VibriophageVf33, Vibrio 35 Primary Atypical Pneumonia Mycoplasma pneumoniae Klebsiella pneumonia Klebsiella pneumoniae phage VP1, Vibrio phage VP11, Vibrio phage VP3, Vibrio Serratia pneumonia Serraia marCescens phage VP5, Vibrio phage X29, Vicia cryptic virus, Vigna Q Fever coxieia burnetti sinensis mosaic virus, Vilyuisk virus, Vinces virus, Viola Psittacosis chlamydia psittaci Botulism Cliostridium bointinum mottle virus, viper retrovirus, viral haemorrhagic septicemia Staphylococcal Food Stephylococcusatiretts virus, virus-like particle, Visna Maedi virus, Visna virus, 40 Poisoning Voandzeia mosaic virus, Voandzeia necrotic mosaic virus, Clostridial Food Poisoning ciostridium perfinges volepox virus, Wad Medani virus, Wallal virus, Walleye epi Typhoid Fever Salmonella typhi Salmonella Serotypes dermal hyperplasia, Walrus calicivirus, Wanowrie virus, War Shigellosis Shigella Serotypes rego virus, Watermelon chlorotic stunt virus, Watermelon Cholera vibrio choierae curly mottle virus, Watermelon mosaic virus 1, Watermelon 45 Bruceiia Spp. mosaic virus 2, Weddel water-borne virus, Weldona virus, Anthrax Bacilius anthracis Tetanus Cliostridium tetani Wesselsbron virus, West Nile virus, western equine encepha Gas Gangrene ciostridium perfinges litis virus, western equine encephalomyelitis virus, Wexford Bubonic versinia pestis virus, Whataroa virus, Wheat American striate mosaic virus, Relapsing Fever Borreia recurrentis Wheat chlorotic streak virus, Wheat dwarf virus, Wheat 50 Rocky Mountain Spotted Rickettsia rickettsiae Fewer rosette stunt virus, Wheat streak mosaic virus. Wheat yellow (Typhus Rickettsia prowazeki leaf virus, Wheat yellow mosaic virus, White bryony virus, Fever) White clover cryptic virus 1, White clover cryptic virus 2, Endemic Typhus (Murine Rickettsia typhi White clover cryptic virus 3, White clover mosaic virus, Typhus) 55 Scrub Typhus Rickettsia tsutsugamishi White lupinrnosaic virus, Wild cucumber mosaic virus, Wild Rickettsia akari potato mosaic virus, Wildbeest herpesvirus, Wineberry latent Tickborne virus, Winter wheat mosaic virus, Winter wheat Russian Syphilis mosaic virus, Wiseana cervinata virus, Wiseana signata Gonorrhea Chlamydial virus, Wiseana umbraculata virus, Wissadula mosaic virus, Ureaplasmal urethritis Ureaplasma trealytictim Wisteria vein mosaic virus. Witwatersrand virus, Wongal 60 Lymphogranuloma Chlamydia trachomatis virus, Wongorr virus, Winter Vomiting Virus, woodchuck Welcell hepatitis B virus, Woodchuck herpesvirus marmota 1, woolly Vaginitis Gardnerella vaginalis Mycoplasmal urethritis Mycoplasma hominis monkey sarcoma virus, wound tumor virus, WRSV virus, Leprosy (hansen's Mycobacterium leprae WVU virus 2937, WW virus 71 to 212, Wveomyia Smithii Disease) NPV. Wyeomyia virus, Xanthomonas phage Cf, Xanthomo 65 Staphylococcal skin Staphiococcusatiretts nas phage Cflt, Xanthomonas phage RR66, Xanthomonas diseases phage Xf, Xanthomonas phage Xf2, Xanthomonas phage US 8,647,676 B2 51 52 TABLE 1-continued TABLE 4-continued

Human diseases caused by bacteria Human diseases caused by protozoa Disease Casual Agent Disease Causal Agent Trachoma chlamydia trachomatis Bacterial Conjuctivitis Haemophilus influenze type III African Sleeping Sickness Trypanosoma brucei Leishmaniasis (Kala-azar) Leishmania donovani Toxoplasma gondii 10 Malaria Plasmodium spp. TABLE 2 Babesiosis Babesia microti Human diseases caused by virus Pneumocytosis (PCP) Pneumocystis carinii Causal Disease Agent Organs Affected 15 Individual Influenza RNA Respiratory Tract Adenovirus Infections DNA Lungs, Eyes The individual treated can be a human being or an animal. Respiratory Syncytial Disease RNA Respiratory Tract The animal can be a dog, cat, horse, rabbit, hamster, mouse, Rhinovirus Infections RNA Upper Respiratory Tract rat, monkey, cow, pig, donkey, fish, bird, reptile or any other Herpes Simplex DNA Skin, Pharynx, Genital animal in need of treatment. In one embodiment the animal is Organs Chicken pox (Varicella) DNA Skin, Nervous System a laboratory/test animal. In another embodiment the animal in Measles (Rubeola) RNA Respiratory Tract, Skin need of treatment is a pet or livestock Such as domesticated German Measles (Rubella) RNA Skin cows, pigs, sheep, poultry or farmed fish. Mumps (Epidemic Parotitis) RNA Salivary Glands, Blood Small Pox (Variola) DNA Skin, Blood The human being can be a man, a woman, a post-meno Warts Kawasaki Disease DNA Skin 25 pausal women, a pregnant woman, a lactating woman, an Yellow Fever RNA Liver, Blood Dengue Fever RNA Blood, Muscles infant, a child, or an adult. The individual such as a human Hepatitis A RNA Liver being can be of any age such as from newborn to 120 years Hepatitis B DNA Liver old, for example from 0 to 6 months, such as from 6 to 12 NANB Hepatitis RNA Liver Viral Gastroenteritis Many RNA Intestine months, for example from 1 to 5 years, such as from 5 to 10 Viruses 30 years, for example from 10 to 15 years, such as from 15 to 20 Viral Fevers Many RNA Blood years, for example from 20 to 25 years, such as from 25 to 30 Viruses Cytomegalovirus Disease DNA Blood, Lungs years, for example from 30 to 35 years, such as from 35 to 40 AIDS Retrovirus T-lymphocytes years, for example from 40 to 45 years, such as from 45 to 50 (RNA) years, for example from 50 to 60 years, such as from 60 to 70 Rabies RNA Brain, Spinal cord 35 years, for example from 70 to 80 years, such as from 80 to 90 Polio RNA intestine, Brain, Spinal Cord years, for example from 90 to 100 years, such as from 100 to Slow Virus Disease Prions Brain 110 years, for example from 110 to 120 years. Arboviral Enephalitis Many RNA Brain viruses The individual can be of any race Such as a Caucasian, a 40 black person, an East Asian person, a person of Mongoloid race, a person of Ethiopian race, a person of Negroid race, a person of American Indian race, a person of Australoid race, TABLE 3 or a person of Malayan race. Human diseases caused by fungi Said human being or animal can be healthy or have one or 45 more diseases. Said human being or animal can be diagnosed Disease Casual Agent and/or treated for one or more diseases. In one embodiment Cryptococci is neoformans said individual is genetically disposed for one or more dis Candidiasis, Vaginitis, Thrush, Candida albicans Onychia CaSCS. tinea Pedis Trichophyton Spp. 50 In one embodiment, the individual in need of treatment is a Tinea Captis Microsporum Spp. Tinea Corporis,Tinea Barhae Epidermophyton spp. individual infected with one or more pathogenic or disease Histoplasmosis Histoplasma capsulatin causing bacteria. Disease-causing bacteria include, but are Blastomycosis Blastomyces dermatitidis not limited to the group comprising Pseudomonas, Entero Coccidiodomycosis Coccidiodes immitis Aspergillosis Otomycosis Aspergillus coccus, Listeria, Bacillus, Staphylococcus, Escherichia, Sal 55 monella and Clostridium. In a preferred embodiment the bacteria are selected from the group comprising Pseudomo nas aeruginosa, Enterococcus faecalis, Listeria monocytoge TABLE 4 nes, Bacillus cereus, Staphylococcus aureus, Escherichia Human diseases caused by protozoa coli, Salmonella berta, Clostridium perfingens and 60 Clostridium bifermentans. Disease Causal Agent In one embodiment, the individual in need of treatment is a Amoebiasis Entamoeba histolytica individual infected with one or more bacteria resistant to one Primary Amoebic Naegleria fowleri or more antibiotics. Examples of resistant or multiresistant Giardiasis Giardia Lambia 65 bacteria include but are not limited to meticillin-resistant S. aureus, and multiresistant Paeruginosa, Klebsiella pneumo niae and Acinetobacter. US 8,647,676 B2 53 54 In another embodiment, the individual in need of treatment Injections may be either systemic or local injections is a individual infected with one or more pathogenic fungi. Other administration modes of the present invention Administration Route and Dosage include: The composition may be administered using one or more Jet-infusion (micro-drops, micro-spheres, micro-beads) of the following routes of administration. through skin Routes of administration can broadly be divided into: Drinking Solution, Suspension or gel Topical: local effect, substance is applied directly where its Inhalation action is desired. Nose-drops Enteral: desired effect is systemic (non-local), Substance is Eye-drops given via the digestive tract. 10 Ear-drops Parenteral: desired effect is systemic, substance is given by Skin application as ointment, gel, lotion, cream or through routes other than the digestive tract. a patch In one embodiment the antimicrobial composition of the Vaginal application as ointment, gel, creme or washing present invention is administered topically. Gastro-Intestinal flushing In one embodiment the antimicrobial composition of the 15 Rectal washings or by use of Suppositories present invention is administered enterally. Administration can be performed as In one embodiment the antimicrobial composition of the Single administration Such as single intake, injection, present invention is administered parentally. application, washing Topical administration include: Multiple administrations such as multiple intakes, injec Epicutaneous (application onto the skin tions, applications, washings Inhalational On single day basis Enema Over prolonged time as days, month, years Eye drops (onto the conjunctiva) Drug dose and regimen can be modified during the course. Ear drops A dose or dosage of the composition according to the Intranasal route (into the nose), 25 present invention may be given as a single dose or in divided Vaginal doses. A single dose occurs only once, with the drug admin Enteral administration is any form of administration that istered either as a bolus or by continuous infusion. Alterna involves any part of the and include: tively, the dose may be divided into multiple doses and given By mouth (peroral) recurrently, such as twice (two times), for example three By gastric feeding tube, duodenal feeding tube, or gastros 30 times, such as four times, for example five times, such as six tomy times, for example seven times, such as eight times, for Rectally example nine times, such as ten divided doses. Furthermore, Parenteral by injection or infusion include: the dose may be given repeatedly, i.e. more than once, Such as Intravenous (into a vein) twice (two times), for example three times, such as four times, Intraarterial (into an artery) 35 for example five times, such as six times, for example seven Intramuscular (into a muscle), times, such as eight times, for example nine times, such as ten Intracerebral (into the cerebrum) direct injection into the times a day. Alternatively, the dose may be in Sustained brain. release form. A bolus is in theory regarded as given immedi Intracerebroventricular (into the cerebral ventricles) ately, and should be administered in less than 5 minutes. administration into the ventricular system of the brain 40 It follows that the composition according to the present Intracardiac (into the heart) invention may be given once or more daily, or alternatively Subcutaneous (under the skin), may be given with intervals of 1 day, Such as 2 days, for Intraosseous infusion (into the bone marrow) is, in effect, example 3 days, such as 4 days, such as 5 days, for example 6 an indirect intravenous access because the bone marrow days. Such as 7 days (1 week), for example 8 days, such as 9 drains directly into the venous system. 45 days. Such as 10 days, for example 11 days, such as 12 days, Intradermal, (into the skin itself) for example 13 days, such as 14 days (2 weeks), Such as 3 Intrathecal (into the spinal canal) weeks, for example 4 weeks, such as 5 weeks, for example 6 Intraperitoneal, (infusion or injection into the peritoneum) weeks, such as 7 weeks, such as 8 weeks, for example 12 Intravesical infusion is into the urinary bladder. weeks. Intracavernosal injection is into the base of the penis. 50 In one embodiment the antimicrobial composition accord Other parenteral administration modes include: ing to the present invention is administered to an individual in Transdermal (diffusion through the intact skin), need thereof at a total daily dosage of from about 0.01 milli Transmucosal (diffusion through a mucous membrane), gram to about 1000 milligram per kilogram of body weight. e.g. insufflation, Sublingual, i.e. under the tongue, vagi The dosage regimen may be adjusted within this range or even nal Suppositories 55 outside of this range to provide the optimal therapeutic Inhalational, response. Intracisternal: given between the first and second cervical The composition according to the present invention is vertebrae given in an effective amount to an individual in need thereof. Other epidural (synonym: peridural) (injection or infusion The amount of composition according to the present inven into the epidural space) 60 tion in one preferred embodiment is in the range of from about Intravitreal, through the eye 0.01 milligram per kg body weight per dose to about 1000 Peroral intake may be in the form of milligram per kg body weight per dose, such as from about Tablets 0.01 milligram per kg body weight per dose to about 0.025 Capsules milligram per kg body weight per dose, for example from Mixtures 65 about 0.025 milligram per kg body weight per dose to about Liquid 0.05 milligram per kg body weight per dose. Such as from Powder about 0.05 milligram per kg body weight per dose to about US 8,647,676 B2 55 56 0.075 milligram per kg body weight per dose, for example body weight per dose to about 10 milligram per kg body from about 0.075 milligram per kg body weight per dose to weight per dose. Such as from about 1.4 milligram per kg about 0.1 milligram per kg body weight per dose, such as body weight per dose to about 10 milligram per kg body from about 0.1 milligram per kg body weight per dose to weight per dose, for example from about 1.6 milligram per kg about 0.25 milligram per kg body weight per dose, such as body weight per dose to about 10 milligram per kg body from about 0.25 milligram per kg body weight per dose to weight per dose. Such as from about 1.8 milligram per kg about 0.5 milligram per kg body weight per dose, for example body weight per dose to about 10 milligram per kg body from about 0.5 milligram per kg body weight per dose to weight per dose, for example from about 2.0 milligram per kg about 0.75 milligram per kg body weight per dose, such as body weight per dose to about 10 milligram per kg body from about 0.75 milligram per kg body weight per dose to 10 weight per dose. Such as from about 2.2 milligram per kg about 1.0 milligram per kg body weight per dose, for example body weight per dose to about 10 milligram per kg body from about 1.0 milligram per kg body weight per dose to weight per dose, for example from about 2.4 milligram per kg about 2.5 milligram per kg body weight per dose, such as body weight per dose to about 10 milligram per kg body from about 2.5 milligram per kg body weight per dose to weight per dose. Such as from about 2.6 milligram per kg about 5 milligram per kg body weight per dose, for example 15 body weight per dose to about 10 milligram per kg body from about 5 milligram per kg body weight per dose to about weight per dose, for example from about 2.8 milligram per kg 7.5 milligram per kg body weight per dose, such as from body weight per dose to about 10 milligram per kg body about 7.5 milligram per kg body weight per dose to about 10 weight per dose. Such as from about 3.0 milligram per kg milligram per kg body weight per dose, for example from body weight per dose to about 10 milligram per kg body about 10 milligram per kg body weight per dose to about 25 weight per dose, for example from about 3.2 milligram per kg milligram per kg body weight perdose. Such as from about 25 body weight per dose to about 10 milligram per kg body milligram per kg body weight per dose to about 50 milligram weight per dose. Such as from about 3.4 milligram per kg per kg body weight per dose. Such as from about 50 milligram body weight per dose to about 10 milligram per kg body per kg body weight per dose to about 75 milligram per kg weight per dose, for example from about 3.6 milligram per kg body weight per dose, for example from about 75 milligram 25 body weight per dose to about 10 milligram per kg body per kg body weight per dose to about 100 milligram per kg weight per dose. Such as from about 3.8 milligram per kg body weight per dose, such as from about 100 milligram per body weight per dose to about 10 milligram per kg body kg body weight per dose to about 250 milligram per kg body weight per dose, for example from about 4.0 milligram per kg weight per dose, for example from about 250 milligram per body weight per dose to about 10 milligram per kg body kg body weight per dose to about 500 milligram per kg body 30 weight per dose. Such as from about 4.2 milligram per kg weight per dose, such as from about 500 milligram per kg body weight per dose to about 10 milligram per kg body body weight per dose to about 750 milligram per kg body weight per dose, for example from about 4.4 milligram per kg weight per dose, for example from about 750 milligram per body weight per dose to about 10 milligram per kg body kg body weight per dose to about 1000 milligram per kg body weight per dose. Such as from about 4.6 milligram per kg weight per dose. 35 body weight per dose to about 10 milligram per kg body The amount of composition according to the present inven weight per dose, for example from about 4.8 milligram per kg tion in another preferred embodiment is in the range of from body weight per dose to about 10 milligram per kg body about 0.01 milligram per kg body weight per dose to about 20 weight per dose. Such as from about 5.0 milligram per kg milligram per kg body weight per dose, such as from about body weight per dose to about 10 milligram per kg body 0.02 milligram per kg body weight per dose to about 18 40 weight per dose, for example from about 5.2 milligram per kg milligram per kg body weight per dose, for example from body weight per dose to about 10 milligram per kg body about 0.04 milligram per kg body weight per dose to about 16 weight per dose. Such as from about 5.4 milligram per kg milligram per kg body weight per dose, such as from about body weight per dose to about 10 milligram per kg body 0.06 milligram per kg body weight per dose to about 14 weight per dose, for example from about 5.6 milligram per kg milligram per kg body weight per dose, for example from 45 body weight per dose to about 10 milligram per kg body about 0.08 milligram per kg body weight per dose to about 12 weight per dose. Such as from about 5.8 milligram per kg milligram per kg body weight per dose, such as from about body weight per dose to about 10 milligram per kg body 0.1 milligram per kg body weight per dose to about 10 milli weight per dose, for example from about 6.0 milligram per kg gram per kg body weight per dose, such as from about 0.2 body weight per dose to about 10 milligram per kg body milligram per kg body weight per dose to about 10 milligram 50 weight per dose. Such as from about 6.2 milligram per kg per kg body weight per dose, for example from about 0.3 body weight per dose to about 10 milligram per kg body milligram per kg body weight per dose to about 10 milligram weight per dose, for example from about 6.4 milligram per kg per kg body weight per dose. Such as from about 0.4 milli body weight per dose to about 10 milligram per kg body gram per kg body weight per dose to about 10 milligram per weight per dose. Such as from about 6.6 milligram per kg kg body weight per dose, for example from about 0.5 milli 55 body weight per dose to about 10 milligram per kg body gram per kg body weight per dose to about 10 milligram per weight per dose, for example from about 6.8 milligram per kg kg body weight per dose, such as from about 0.6 milligram body weight per dose to about 10 milligram per kg body per kg body weight per dose to about 10 milligram per kg weight per dose. Such as from about 7.0 milligram per kg body weight per dose, for example from about 0.7 milligram body weight per dose to about 10 milligram per kg body per kg body weight per dose to about 10 milligram per kg 60 weight per dose, for example from about 7.2 milligram per kg body weight per dose. Such as from about 0.8 milligram per body weight per dose to about 10 milligram per kg body kg body weight per dose to about 10 milligram per kg body weight per dose. Such as from about 7.4 milligram per kg weight per dose, for example from about 0.9 milligram per kg body weight per dose to about 10 milligram per kg body body weight per dose to about 10 milligram per kg body weight per dose, for example from about 7.6 milligram per kg weight per dose. Such as from about 1.0 milligram per kg 65 body weight per dose to about 10 milligram per kg body body weight per dose to about 10 milligram per kg body weight per dose. Such as from about 7.8 milligram per kg weight per dose, for example from about 1.2 milligram per kg body weight per dose to about 10 milligram per kg body US 8,647,676 B2 57 58 weight per dose, for example from about 8.0 milligram per kg about 8 milligram per kg body weight per dose. Such as from body weight per dose to about 10 milligram per kg body about 0.2 milligram per kg body weight per dose to about 6 weight per dose. Such as from about 0.2 milligram per kg milligram per kg body weight per dose, for example from body weight perdose to about 8 milligram per kg body weight about 0.3 milligram per kg body weight per dose to about 6 per dose, for example from about 0.3 milligram per kg body 5 milligram per kg body weight per dose, such as from about weight per dose to about 8 milligram per kg body weight per 0.4 milligram per kg body weight per dose to about 6 milli dose. Such as from about 0.4 milligram per kg body weight gram per kg body weight per dose, for example from about per dose to about 8 milligram per kg body weight per dose, for 0.5 milligram per kg body weight per dose to about 6 milli example from about 0.5 milligram per kg body weight per gram per kg body weight per dose, such as from about 0.6 dose to about 8 milligram per kg body weight per dose. Such 10 milligram per kg body weight per dose to about 6 milligram as from about 0.6 milligram per kg body weight per dose to per kg body weight per dose, for example from about 0.7 about 8 milligram per kg body weight per dose, for example milligram per kg body weight per dose to about 6 milligram from about 0.7 milligram per kg body weight per dose to per kg body weight per dose, such as from about 0.8 milli about 8 milligram per kg body weight per dose. Such as from gram per kg body weight per dose to about 6 milligram per kg about 0.8 milligram per kg body weight per dose to about 8 15 body weight per dose, for example from about 0.9 milligram milligram per kg body weight per dose, for example from per kg body weight perdose to about 6 milligram per kg body about 0.9 milligram per kg body weight per dose to about 8 weight per dose. Such as from about 1.0 milligram per kg milligram per kg body weight per dose, such as from about body weight perdose to about 6 milligram per kg body weight 1.0 milligram per kg body weight per dose to about 8 milli per dose, for example from about 1.2 milligram per kg body gram per kg body weight per dose, for example from about weight per dose to about 6 milligram per kg body weight per 1.2 milligram per kg body weight per dose to about 8 milli dose. Such as from about 1.4 milligram per kg body weight gram per kg body weight per dose, such as from about 1.4 per dose to about 6 milligram per kg body weight per dose, for milligram per kg body weight per dose to about 8 milligram example from about 1.6 milligram per kg body weight per per kg body weight per dose, for example from about 1.6 dose to about 6 milligram per kg body weight per dose. Such milligram per kg body weight per dose to about 8 milligram 25 as from about 1.8 milligram per kg body weight per dose to per kg body weight per dose. Such as from about 1.8 milli about 6 milligram per kg body weight per dose, for example gram per kg body weight per dose to about 8 milligram per kg from about 2.0 milligram per kg body weight per dose to body weight per dose, for example from about 2.0 milligram about 6 milligram per kg body weight per dose. Such as from per kg body weight per dose to about 8 milligram per kg body about 2.2 milligram per kg body weight per dose to about 6 weight per dose. Such as from about 2.2 milligram per kg 30 milligram per kg body weight per dose, for example from body weight perdose to about 8 milligram per kg body weight about 2.4 milligram per kg body weight per dose to about 6 per dose, for example from about 2.4 milligram per kg body milligram per kg body weight per dose, such as from about weight per dose to about 8 milligram per kg body weight per 2.6 milligram per kg body weight per dose to about 6 milli dose. Such as from about 2.6 milligram per kg body weight gram per kg body weight per dose, for example from about per dose to about 8 milligram per kg body weight per dose, for 35 2.8 milligram per kg body weight per dose to about 6 milli example from about 2.8 milligram per kg body weight per gram per kg body weight per dose, such as from about 3.0 dose to about 8 milligram per kg body weight per dose. Such milligram per kg body weight per dose to about 6 milligram as from about 3.0 milligram per kg body weight per dose to per kg body weight per dose, for example from about 3.2 about 8 milligram per kg body weight per dose, for example milligram per kg body weight per dose to about 6 milligram from about 3.2 milligram per kg body weight per dose to 40 per kg body weight per dose. Such as from about 3.4 milli about 8 milligram per kg body weight per dose. Such as from gram per kg body weight per dose to about 6 milligram per kg about 3.4 milligram per kg body weight per dose to about 8 body weight per dose, for example from about 3.6 milligram milligram per kg body weight per dose, for example from per kg body weight perdose to about 6 milligram per kg body about 3.6 milligram per kg body weight per dose to about 8 weight per dose. Such as from about 3.8 milligram per kg milligram per kg body weight per dose, such as from about 45 body weight perdose to about 6 milligram per kg body weight 3.8 milligram per kg body weight per dose to about 8 milli per dose, for example from about 4.0 milligram per kg body gram per kg body weight per dose, for example from about weight per dose to about 6 milligram per kg body weight per 4.0 milligram per kg body weight per dose to about 8 milli dose. Such as from about 4.2 milligram per kg body weight gram per kg body weight per dose, such as from about 4.2 per dose to about 6 milligram per kg body weight per dose, for milligram per kg body weight per dose to about 8 milligram 50 example from about 4.4 milligram per kg body weight per per kg body weight per dose, for example from about 4.4 dose to about 6 milligram per kg body weight per dose. Such milligram per kg body weight per dose to about 8 milligram as from about 4.6 milligram per kg body weight per dose to per kg body weight per dose. Such as from about 4.6 milli about 6 milligram per kg body weight per dose, for example gram per kg body weight per dose to about 8 milligram per kg from about 4.8 milligram per kg body weight per dose to body weight per dose, for example from about 4.8 milligram 55 about 6 milligram per kg body weight per dose. Such as from per kg body weight per dose to about 8 milligram per kg body about 5.0 milligram per kg body weight per dose to about 6 weight per dose. Such as from about 5.0 milligram per kg milligram per kg body weight per dose. body weight perdose to about 8 milligram per kg body weight Co-Administration with One or More Drugs per dose, for example from about 5.2 milligram per kg body The composition according to the present invention can be weight per dose to about 8 milligram per kg body weight per 60 co-administered to an individual in need thereof in combina dose. Such as from about 5.4 milligram per kg body weight tion with one or more drugs such as one or more drugs with per dose to about 8 milligram per kg body weight per dose, for antimicrobial effect. example from about 5.6 milligram per kg body weight per The composition according to the present invention can be dose to about 8 milligram per kg body weight per dose. Such co-administered to an individual in need thereof in combina as from about 5.8 milligram per kg body weight per dose to 65 tion with one or more antibiotics. The one or more antibiotics about 8 milligram per kg body weight per dose, for example can be selected from the group consisting of Amikacin disul from about 6.0 milligram per kg body weight per dose to fate salt, Amikacin hydrate, Anisomycin from Streptomyces US 8,647,676 B2 59 60 griseolus, Apramycin Sulfate salt, Azithromycin, Blasticidine platinum(II) dichloride, Coumermycin A1, Cytochalasin B S hydrochloride, Brefeldin A, Brefeldin A from Penicillium Helminthosporium dematioideum, Cytochalasin D Zygospo brefeldianum, Butirosin sulfate salt, Butirosin A from Bacil rium mansonii, Dacarbazine, Daunorubicin hydrochloride, lus vitellinus, Chloramphenicol, Chloramphenicol base, Daunorubicin hydrochloride USP Distamycin A hydrochlo Chloramphenicol Succinate sodium salt, Chlortetracycline ride from Streptomyces distallicus, Doxorubicin hydrochlo hydrochloride, Chlortetracycline hydrochloride from Strep ride, Echinomycin, Echinomycin BioChemika, Enrofloxacin tomyces aureofaciens, Clindamycin 2-phosphate, Clindamy BioChemika, Etoposide, Etoposide solid, Flumequine. For cin hydrochloride, Clotrimazole, Cycloheximide from micro mycin, Fumagillin from Aspergillus filmigatus, Ganciclovir, bial, Demeclocycline hydrochloride, Dibekacin sulfate salt, Gliotoxin from Gliocladium fimbriatum, Lomefloxacin Dihydrostreptomycin sesquisulfate, Dihydrostreptomycin 10 hydrochloride, Metronidazole purum, Mithramycin A from Solution, Doxycycline hyclate. Duramycin from Streptover Streptomyces plicatus, Mitomycin C Streptomyces caespito ticillium cinnamoneus, Emetime dihydrochloride hydrate), sus, Nalidixic acid, Nalidixic acid sodium salt, Nalidixic acid Erythromycin, Erythromycin USP, Erythromycin powder, sodium salt powder, Netropsin dihydrochloride hydrate, Erythromycin, Temephos, Erythromycin estolate, Erythro Nitrofurantoin, Nogalamycin from Streptomyces nogalater, mycin ethyl succinate, Erythromycin standard solution, 15 Nonactin from Streptomyces tsusimaensis, Novobiocin Erythromycin stearate, Fusidic acid sodium salt, G 418 dis sodium salt, Ofloxacin, Oxolinic acid, Paclitaxel from Taxus ulfate salt, G 418 disulfate salt powder, G 418 disulfate salt vannanensis, Paclitaxel from Taxus brevifolia, Phenazine Solution liquid, Gentamicin Solution liquid, Gentamicin Solu methosulfate, Phleomycin Streptomyces verticillus, Pipe tion, Gentamicin Sulfate Micromonospora purpurea, Gen midic acid, Rebeccamycin from Saccharothrix aerocoloni tamicin sulfate salt, Gentamicin sulfate salt powder USP genes, Sineflungin, Streptonigrin from Streptomyces floccu Gentamicin-Glutamine solution liquid, Helvolic acid from lus, Streptozocin, Succinylsulfathiazole, Sulfadiazine, Cephalosporium caerulens, Hygromycin B Streptomyces Sulfadimethoxine, Sulfaguanidine purum, Sulfamethazine, hygroscopicus, Hygromycin B Streptomyces hygroscopicus Sulfamonomethoxine, Sulfanilamide, Sulfaquinoxaline powder, Hygromycin B solution Streptomyces hygroscopi sodium salt, Sulfasalazine, Sulfathiazole sodium salt, Trime cus, Josamycin, Josamycin solution, Kanamycin B Sulfate 25 thoprim, Trimethoprim lactate salt, Tubercidin from Strepto salt, Kanamycin disulfate salt from Streptomyces kana myces tubercidicus, 5-AZacytidine, Cordycepin, Formycin A, myceticus, Kanamycin monosulfate from Streptomyces kana (+)-6-Aminopenicillanic acid, 7-Aminodesacetoxycepha myceticus, Kanamycin monosulfate from Streptomyces kana losporanic acid. , Ampicillin, Ampicillin Sodium myceticus powder USP, Kanamycin solution from salt, Ampicillin trihydrate, Ampicillin trihydrate USP Streptomyces kanamyceticus, Kirromycin from Streptomyces 30 Azlocillin sodium salt, Bacitracin Bacillus licheniformis, collinus, Lincomycin hydrochloride, Lincomycin standard Bacitracin Zinc salt Bacillus licheniformis, Carbenicillin solution, Meclocycline sulfosalicylate salt, Mepartricin, disodium salt, Cefaclor, Cefamandole lithium salt, Cefaman Midecamycin from Streptomyces mycarofaciens, Minocy dole nafate, Cefamandole Sodium salt, Cefazolin Sodium salt, cline hydrochloride crystalline, Neomycin solution, Neomy Cefinetazole sodium salt, CefoperaZone sodium salt, Cefo cin trisulfate salt hydrate, Neomycin trisulfate salt hydrate 35 taxime sodium salt, Cefsulodin sodium salt, Cefsulodin powder, Neomycin trisulfate salt hydrate USP powder, Sodium salt hydrate, sodium salt, Cephalexin Netilmicin sulfate salt, Nitrofurantoin crystalline, Nourseo hydrate, Cephalosporin C Zinc salt, Cephalothin Sodium salt, thricin Sulfate, Oleandomycin phosphate salt, Oleandomycin Cephapirin Sodium salt, Cephradine, Cloxacillin Sodium salt, triacetate, Oxytetracycline dihydrate, Oxytetracycline hemi Cloxacillin sodium salt monohydrate, D-(-)-Penicillamine calcium salt, Oxytetracycline hydrochloride, Paromomycin 40 hydrochloride, D-Cycloserine microbial, D-Cycloserine sulfate salt, Puromycin dihydrochloride from Streptomyces powder, Dicloxacillin sodium salt monohydrate, D-Penicil alboniger, Rapamycin from Streptomyces hygroscopicus, lamine, Econazole nitrate salt, Ethambutol dihydrochloride, Ribostamycin sulfate salt, Rifampicin, Rifamycin SV sodium Lysostaphin from Staphylococcus staphylolyticus, Moxalac salt, Rosamicin Micromonospora rosaria, Sisomicin Sulfate tam sodium salt, Nafcillin sodium salt monohydrate, Nikko salt, Spectinomycin dihydrochloride hydrate, Spectinomycin 45 mycin, Nikkomycin Z Streptomyces tendae, Nitrofurantoin dihydrochloride hydrate powder, Spectinomycin dihydro crystalline, Oxacillin sodium salt, Penicillic acid powder, chloride pentahydrate, Spiramycin, Spiramycin from Strep G potassium salt, Penicillin G potassium salt pow tomyces sp., Spiramycin solution, Streptomycin solution, der, Penicillin G potassium salt, Penicillin G sodium salt Streptomycin sulfate salt, Streptomycin sulfate salt powder, hydrate powder, Penicillin G sodium salt powder, Penicillin Tetracycline, Tetracycline hydrochloride, Tetracycline 50 G sodium salt, Phenethicillin potassium salt, Phenoxymeth hydrochloride USP. Tetracycline hydrochloride powder, ylpenicillinic acid potassium salt, Phosphomycin disodium Thiamphenicol. Thiostrepton from Streptomyces azureus, salt, Pipemidic acid, Piperacillin sodium salt, Ristomycin Tobramycin, Tobramycin Sulfate salt, Tunicamycin A monosulfate, Vancomycin hydrochloride from Streptomyces homolog, Tunicamycin C homolog, Tunicamycin Strepto orientalis, 2-Mercaptopyridine N-oxide sodium salt, 4-Bro myces sp., Tylosin Solution, Tylosin tartrate, Viomycin Sulfate 55 mocalcimycin A23.187 BioChemika, Alamethicin Tricho salt, Virginiamycin M, (S)-(+)-Camptothecin, 10-Deacetyl derma viride, Amphotericin B Streptomyces sp., Amphoteri baccatin III from Taxus baccata, 5-AZacytidine, 7-Aminoac cin B preparation, Calcimycin A23 187, Calcimycin A23 187 tinomycin D, 8-Quinolinol crystalline, 8-Quinolinol hemicalcium-magnesium) salt, Calcimycin A23.187 hemi hemisulfate salt crystalline, 9-Dihydro-13-acetylbaccatin III calcium salt, Calcimycin A23.187 hemimagnesium salt, from Taxus canadensis, Aclarubicin, Aclarubicin hydrochlo 60 Chlorhexidine diacetate salt monohydrate, Chlorhexidine ride, Actinomycin D from Streptomyces sp., Actinomycin I diacetate salt hydrate, Chlorhexidine digluconate, Clotrima from Streptomyces antibioticus, Actinomycin V from Strep Zole, Colistin Sodium methanesulfonate, Colistin Sodium tomyces antibioticus, Aphidicolin Nigrospora sphaerica, methanesulfonate from Bacillus collistinus, Colistin sulfate Bafilomycin A1 from Streptomyces griseus, Bleomycin Sul salt, Econazole nitrate salt, Hydrocortisone 21-acetate, Fil fate from Streptomyces verticillus, Capreomycin sulfate from 65 ipin complex Streptomyces filipinensis, Gliotoxin from Glio Streptomyces capreolus, Chromomycin A Streptomyces gri cladium fimbriatum, Gramicidin A from Bacillus brevis, Seus, Cinoxacin, Ciprofloxacin BioChemika, cis-Diammine Gramicidin C from Bacillus brevis, Gramicidin from Bacillus US 8,647,676 B2 61 62 aneurinolyticus (Bacillus brevis), lonomycin calcium salt Bevirimat, BILN 2061, Brecanavir, Brivudine, Calanolide A, Streptomyces conglobatus, Lasalocid A Sodium salt, Lono Capravirine, Cidofovir, Combivir, Condylox, Cyanovirin-N. mycin A Sodium salt from Streptomyces ribosidificus, Mon Darunavir, Delavirdine, DexelVucitabine, Diarylpyrimidines, ensin sodium salt, N-(6-Aminohexyl)-5-chloro-1-naphthale Didanosine, Docosanol, Edoxudine, Efavirenz, Elvitegravir, nesulfonamide hydrochloride, Narasin from Streptomyces Elvucitabine, Emivirine, Emtricitabine, Enfluvirtide, Ente auriofaciens, Nigericin Sodium salt from Streptomyces cavir, Epigallocatechin gallate, Etravirine, Famciclovir, hygroscopicus, Nisin from Streptococcus lactis, Nonactin Fialuridine, Fomivirsen, Fosamprenavir, Foscarnet, Fosfo from Streptomyces sp., Nystatin, Nystatin powder, Phenazine net, Fusion inhibitor, Ganciclovir, Gardasil, Globoidnan A, methosulfate, Pimaricin, Pimaricin from Streptomyces chat Griffithsin, GS-9137, Ibacitabine, Ibalizumab, Immunovir, tanoogensis, Polymyxin B solution, Polymyxin B sulfate salt, 10 Idoxuridine, Imiquimod, Indinavir, Inosine, Interferon DL-Penicillamine acetone adduct hydrochloride monohy gamma, Interferon type III, Interferon type II. Interferon type drate, Polymyxin B sulfate salt powder USP Praziquantel, I, Interferon, Lamivudine, Lodenosine, Lopinavir, Loviride, Salinomycin from Streptomyces albus, Salinomycin from MK-0518, Maraviroc, Miltefosine, Moroxydine, Nelfinavir, Streptomyces albus, Surfactin from Bacillus subtilis, Valino Nevirapine, Nexavir, Oragen, Oseltamivir, Penciclovir, Per mycin, (+)-USnic acid from Usnea dasypoga, (t)-Micona 15 amivir, Pleconaril, Podophyllotoxin, Portmanteau inhibitors, Zole nitrate salt, (S)-(+)-Camptothecin, 1-Deoxymannojiri PRO 140, Quinotaline, Racivir, Raltegravir, Ribavirin, mycin hydrochloride, 1-Deoxynojirimycin hydrochloride, Rilpivirine, Rimantadine, Ritonavir, R-roscovitine, 2-Heptyl-4-hydroxyquinoline N-oxide, Cordycepin, 1.10 Saquinavir, SCH 503034, Stampidine, Stavudine, Taribavi Phenanthroline hydrochloride monohydrate puriss., 6-Diazo rin, Telbivudine, Tenofovir, Tenofovir disoproxil, Tipranavir, 5-oxo-L-norleucine, 8-Quinolinol crystalline, 8-Quinolinol Trifluridine, Trizivir, Tromantadine, Truvada, Valaciclovir, hemisulfate salt, Antimycin A from Streptomyces sp., Anti Valganciclovir, Vicriviroc, Vidarabine, Viramidine, Vivecon, mycin A, Antimycin A2, Antimycin A. Antipain, Ascomy VX 950/Telaprevir, Zalcitabine, Zanamivir, and Zidovudine cin, AZaserine, Bafilomycin A1 from Streptomyces griseus, (AZT). Bafilomycin B1 from Streptomyces species, Cerulenin Bio The composition according to the present invention can be Chemika, Chloroquine diphosphate salt, Cinoxacin, Ciprof 25 co-administered to an individual in need thereof in combina loxacin, Mevastatin BioChemika, Concanamycin A, Con tion with one or more antifungal drugs. The one or more canamycin A Streptomyces sp. Concanamycin C from antifungal drugs can be selected from the group consisting of Streptomyces species, Coumermycin A1, Cyclosporin Afrom polyene antimycotics such as Natamycin, Rimocidin, Filipin, Tolypocladium inflatum, Cyclosporin A, Econazole nitrate Nystatin, Amphotericin B, and Candicin, imidazole and tria salt, Enrofloxacin, Etoposide, Flumequine, Formycin A, 30 Zole antifungal drugs such as Imidazoles like Miconazole Furazolidone, Fusaric acid from Gibberella fijikuroi, (Miconazole nitrate), Ketoconazole, Clotrimazole (marketed Geldanamycin from Streptomyces hygroscopicus, Gliotoxin as Lotrimin, Canesten in the UK), Econazole, Bifonazole, from Gliocladium fimbriatum, Gramicidin A from Bacillus Butoconazole, Fenticonazole, Isoconazole, Oxiconazole, brevis, Gramicidin C from Bacillus brevis, Gramicidin from Sertaconazole (marketed as Ertaczo), Sulconazole, Tiocona Bacillus aneurinolyticus (Bacillus brevis), Gramicidin from 35 Zole, Fluconazole, Itraconazole, Isavuconazole, Ravucona Bacillus brevis, Herbimycin A from Streptomyces hygro Zole, Posaconazole, Voriconazole, and Terconazole, Ally scopicus, Indomethacin, Irgasan, Lomefloxacin hydrochlo lamines Such as Terbinafine (marketed as Lamisil), ride, Mycophenolic acid powder, Myxothiazol BioChemika, Amorolfine, Naftifine (marketed as Naftin), and Butenafine N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide (marketed as Lotrimin Ultra), Echinocandins such as Anidu hydrochloride, Nalidixic acid, Netropsin dihydrochloride 40 lafungin, Caspofungin, and Micafungin, Benzoic acid in hydrate, Niclosamide, Nikkomycin BioChemika, Nikkomy combination with a keratolytic agent (such as in Whitfields cin Z Streptomyces tendae, N-Methyl-1-deoxynojirimycin, Ointment), Ciclopirox olamine, Flucytosine, or 5-fluorocy Nogalamycin from Streptomyces nogalater, Nonactin D80% tosine, Griseofulvin, and Gentian Violet Haloprogin Tolnaf from Streptomyces tsusimaensis, Nonactin from Streptomy tate (marketed as Tinactin, Desenex, Aftate). ces sp., Novobiocin Sodium salt, Ofloxacin, Oleandomycin 45 The composition according to the present invention can be triacetate, Oligomycin Streptomyces diastatochromogenes, co-administered to an individual in need thereof in combina Oligomycin A, Oligomycin B. Oligomycin C, Oligomycin tion with one or more antiparasitic drugs. The one or more Streptomyces diastatochromogenes, OXolinic acid, Piericidin antiparasitic drugs can be selected from the group consisting A from Streptomyces mobaraensis, Pipemidic acid, Radici of Antinematodes such as Mebendazole (for most nematode col from Diheterospora chlamydosporia Solid, Rapamycin 50 infections), Pyrantel pamoate (for most nematode infections), from Streptomyces hygroscopicus, Rebeccamycin from Sac Thiabendazole (for roundworm infections), and Diethycarba charothrix aerocolonigenes, Sineflungin, Staurosporine zine (for treatment of Lymphatic filariasis). The method Streptomyces sp., Stigmatellin, Succinylsulfathiazole, Sulfa according to item 197, wherein the one or more antiparasitic diazine, Sulfadimethoxine, Sulfaguanidine purum, Sulfamet drugs comprises Anticestodes such as Niclosamide (for tape hazine, Sulfamonomethoxine, Sulfanilamide, Sulfaquinoxa 55 worm infections), and Praziquantel (for tapeworm infec line sodium salt, Sulfasalazine, Sulfathiazole sodium salt, tions), Antitrematodes such as Praziquantel, Antiamoebics Triacsin C from Streptomyces sp., Trimethoprim, Trimetho Such as Rifampin, Amphotericin B. Clioquinol, Iodoquinol prim lactate salt, Vineomycin A from Streptomyces albO Metronidazole, Tinidazole, Ornidazole, Secnidazole Atova griseolus Subsp., Tectorigenin, and Paracelsin Trichoderma quone, Emetine, Fumagillin, and Trimetrexate, AntiprotoZo reesei. 60 als such as Amphotericin, Antimony, Eflornithine. Furazoli The composition according to the present invention can be done, Melarsoprol, Metronidazole, Miltefosine (Impavido), co-administered to an individual in need thereof in combina Ornidazole, Paromomycin Sulfate, Pentamidine, tion with one or more antiviral drugs. The one or more anti Pyrimethamine, and Tinidazole. viral drugs can be selected from the group consisting of Kit of Parts Abacavir, Aciclovir, Acyclovir, Adefovir, Alferon LDO, 65 In a further embodiment the present invention relates to a Amantadine, Amdoxovir, Ampligen, Amprenavir, Aplaviroc. kit of parts comprising the antimicrobial composition accord Apricitabine, Arbidol, Atazanavir, Ateviridine, Atripla, ing to the present invention. The kit of parts comprises at least US 8,647,676 B2 63 64 one additional component. Such as instructions for use, and/or EXAMPLES one or more drugs for co-administration. Example 1 DETAILED DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the phylogeny of the Crustacea. The closest Preparation of Extracts from C. finmarchicus relatives to Copepoda are the Cephalocarida and the Ostra coda. It is clear from the phylogenetic tree of the Crustacea Catch and Storage of Calanus finnarchicus Subphylum that copepods and decapods are not closely 10 Catch 1 was caught in the fjords of northern Norway. The related. Decapods include many familiar groups, such as catch was frozen onboard the fishing vessel and stored frozen crayfish, crabs, lobsters, prawns and shrimp. until examination. Composition (g/100g): Water: 79.9, pro FIG. 2 shows the Development of the number of viable tein: 11.1, fat: 6.3, ash: 2.0. Salmonella berta cells in Nutrient Broth and Nutrient Broth 15 Catch 2 was caught in Andfjord in northern Norway. The with added 10% aqueous phase from Calanus finmarchicus catch was frozen on board the fishing vessel within one hour (catch 2) during incubation at 37°C. after catch and stored frozen until examination. Composition FIG. 3. HPLC-chromatogram of the anion exchange (g/100 g): Water: 83.0, fat: 5.2. extract. The majority of the compounds including the active Preparation of the Aqueous Phase compound(s) elutes early during the run. This suggests that 100 g frozen sample were thawed at ambient temperature there are mostly polar or charged compounds in the extracts. Furthermore, C18-reversed phase chromatography is not the and then centrifuged at 5.000xG for 10 minutes. The sample preferred method for separating the bioactive peak from con separated into three fractions where the sediment constituted taminants. approximately 60 g, the aqueous phase 38 g and the oil 2 g. FIG. 4. Comparison of analytic chromatography of early 25 The aqueous phase was filtered through a glass fiber filter fractions re-chromatographed on a conventional C18 (left), or (Schleicher & Schull, ref. no. 370003) and then through a polar endcapped C18 (right). Fraction 2 is the lower, and fraction 7 the upper chromatogram. The right panel show micro porous cellulose acetate filter with pore size 0.2 um better separation of the peaks making it possible to distin (Whatman, FP 30/02CA-S). The sterile aqueous phase was guish the different peaks. The active fraction (fraction 4, the 30 stored in sterile capped glass tubes at 4-8°C. third chromatogram counting from below) is separated into four different peaks with the Aquasil column (right panel), The effect of crushing thawed C. finmarchicus in a mortar whereas the conventional C18 column gives no base-line before centrifugation and filtration was examined (data not separation of the same fraction (left panel). shown). The crushing did not affect the antimicrobial activity 35 in the aqueous phase, but resulted in difficulties with the FIG. 5. Chromatogram of the semipreparativ C18-purifi filtration and hence to reduced yields (volume) of filtrate. cation. Similar to the analytical run, the bioactivity eluted Therefore, thawed C. finmarchicus should not be crushed early during the run (see also Table 22). before centrifugation and filtration. FIG. 6. Isocratic normal phase chromatography of the bio active fraction from the semi-preparative reversed phase puri 40 Different filter types were tested, e.g. purified cotton fication (FIG.5). The lower panel is 40/60 and the upper panel (IVBF Hartmann AG, CH 8212, Neuhausen, Switzerland), is 1/99 EtOAc/MeoH. The chromatogram shows that normal glass fiber filters (Schleicher & Schull, ref no. 370003), paper phase gives a good separation of at least 4 different peaks that filters (Schleicher & Schull, Black Ribbon, ref no. 589) and occuras one peak during the reversed phase chromatography. microporous cellulose acetate filters with pore size 0.2 Lum. Normal phase chromatography is probably the best method 45 The main purpose of filtering the aqueous phase after cen for separation of the active compound. trifugation was to remove particles and thus to give a clear FIG. 7. Isocratic normal phase chromatography of the liquid suitable for testing by the BTD method. The antimi active peak from the semi-preparative reversed phase frac crobial composition was not retained by any of the filter tionation (FIG. 5). See Table 22 for bioactivity of the frac materials tested. The clearest liquid was obtained by the tions. The active fraction (4, approximately 3-4 min elution 50 microporous filters, but the flow rate through this filter was time) consists of several compounds, as seen by the shoulders significantly improved by pre-filtering through e.g. glass fiber of the peaks occurring at around 4 minutes. This could be due filters. to the presence of several contaminants, but also several Vari Preparation of Methanol Extract ants of the same compounds. 55 A concentrated composition with increased antimicrobial FIG. 8. UV-spectra of the various peaks from the normal activity is prepared by methanol extraction. phase chromatography shown in FIG. 7. The UV-spectra col lected at different time-points in peak to varied little, Suggest Frozen C. finmarchicus were freeze dried before methanol ing that peak two consists of variants of the same compound. extraction and vacuum evaporation to remove the solvent. The concentrated extract was finally dissolved in deionised FIG. 9. MS-analysis of fraction 4 from FIG.8. When the 60 masses from the background (blank injection) was Sub water and filtered through a micro-porous cellulose acetate tracted, the 245 and 347 peaks stood out as the most interest filter with pore size 0.2 Lum. ing. A comparison of the chemical composition and the anti FIG. 10. MSMS-analysis of the 245-ion. microbial activity of aqueous phase (catch 2) and methanol 65 extract (catch 2) from C. finmarchicus is provided in table 5. FIG. 11. MSMS-analysis of the 347-ion. The antimicrobial activity is much higher in the methanol FIG. 12. The structure of penostatin with a mass=346 Da. extract compared to the aqueous phase. US 8,647,676 B2 65 66 TABLE 5 TABLE 6 Comparison of the chemical composition and the antimicrobial activity Development of turbidity in serial dilutions of aqueous phase from of aqueous phase (catch 2) and methanol extract (catch 2) C. finmarchicus (catch 1) after inoculation with three different from C. finnarchicus test organisms 5 Aqueous phase Methanol extract Dilution Protein (Raw protein 6.7% 68.0% Test organism x 2 x 4 x 8 x 16 x 32 x 64 Water Kjeldahl N*6.25) Ash 2.4% 10.9% E. coi ------Total fat Folch O.S9/o 1.6% 10 S. airetts ------Antimicrobial activity (MIC) 16-32 128 Paeruginosa ------No inoculum +: turbidity, Example 2 -: no turbidity 15 Determination of MIC (Minimal Inhibitory Range of Action Concentration) The range of action of the antimicrobial substance in the aqueous phase extracted from catch 2 was tested by the BTD The activity and presence of antimicrobial Substances in method using nine different test bacteria (P. aeruginosa, E. samples of aqueous phases or methanol extracts were tested faecalis, L. monocytogenes, B. cereus, S. aureus, E. coli, S. by the BTD (Broth Tube Dilution) method, where 2-fold berta, C. perfingens, C. bifermentans and one fungal species serial dilutions of sample insterile water were added the same (C. albicans). All of the test bacteria, which represent Gram +, volume of double strength basis medium inoculated with the Gram -, aerobic and strict anaerobic types, were inhibited individual test organisms. After incubation as specified (table 7). The tested fungal species was not inhibited. below, the test results were read. The lowest concentration (or 25 highest dilution) preventing appearance of turbidity was con TABLE 7 sidered to be the MIC (Minimal Inhibitory Concentration). Development of turbidity in serial dilutions of aqueous phase obtained Preparation of Inoculated Double Strength Basis Media: from C. finmarchicus (catch 2) after inoculation with ten different Clostridia were Pre-Cultivated overnight in LTM (Liquid 30 test organisms Thioglycollate Medium, Oxoid CM173) at 37° C. under anaerobic conditions. All other bacteria were pre-cultivated Dilution overnight in NB (Nutrient Broth, Oxoid CM0067) at 37° C. Test organism x 2 x 4 x 8 x 16 x 32 x 64 Water under aerobic conditions. All fungal species were pre-culti Paeruginosa vated aerobically at 37° C. in NB supplemented with 1% 35 E. faecalis glucose, until visible turbidity. Double strength basis media L. monocytog. were finally inoculated with an amount of pre-culture suffi B. ceretis S. airetts cient to obtain an initial cell density of approximately 10E5/ E. coi m1 to 10E6/ml. S. beria Test organisms: Pseudomonas aeruginosa (ATCC 27853), 40 C. perfingens C. bifermenians Enterococcus faecalis (ATCC 29212), Listeria monocytoge C. albicans (yeast) ------nes (ATCC 7644), Bacillus cereus (CCUG 7414), Staphylo No inoculum coccus aureus (ATCC 25923), Escherichia coli (ATCC +: turbidity, 25922), Salmonella berta (CCUG 27106), Clostridium per -: no turbidity fringens (CCUG 1795), Clostridium bifermentans (CCUG. 45 T36626), MRSA (ATCC 43300), Pseudomonas aeruginosa (multiresistant clinical isolate), Klebsiella pneumoniae (mul Example 4 tiresistant clinical isolate), Acinetobacter (multiresistant clinical isolate), Candida albicans (ATCC 10231), Saccha 50 romyces cerevisiae (bakers yeast), Aspergillus niger (ATCC Inactivation Kinetics 16404). The course of killing was examined by inoculating S. berta Example 3 in 100 ml NB and in 90 ml NB with added 10 ml of aqueous 55 phase extracted from catch 2. The initial cells concentration Detection of Antimicrobial Activity in Aqueous was approximately 10 E5 per ml. The bottles were incubated Phase at 37°C., and aliquots withdrawn during incubation for deter mination of viable aerobic microorganisms (Nordic Commit Antimicrobial activity has been detected in the aqueous tee on Food Analysis no. 86). The bacteria grew well in pure phase from two different catches of C. finnarchicus (June/ 60 NB while in the presence of x10 diluted aqueous phase, the July 2003 and June 2006). number of viable cells underwent reduction. From the for The activity and presence of antimicrobial compounds or mula of the exponential trendline (FIG.2), decimal reduction Substances in the aqueous phase extracted from catch 1 was time could be estimated to 6.8 hours. FIG. 2 shows the Devel tested by the BTD method using three different test bacteria. opment of the number of viable Salmonella berta cells in Growth of all the test bacteria was inhibited. The MIC values 65 Nutrient Broth and Nutrient Broth with added 10% aqueous obtained from the results (table 6) for E. coli, S. aureus and P phase from Calanus finnarchicus (catch 2) during incubation aeruginosa were 8, 16 and 4, respectively. at 37° C. US 8,647,676 B2 67 68 Example 5 alcalase treatment. Therefore, the active one or more antimi crobial compounds in the C. finmarchicus composition is Heat Stability probably not a protein. The heat stability of the antimicrobial substance in aqueous 5 TABLE 10 phase from catch 2 was tested by the BTD method using S. Development of turbidity in serial dilutions of alcalase treated aqueous aureus as a test organism. Heat treatment at 70° C. for 10 phase from C. finmarchicus (catch 2), after inoculation with the test minutes had no effect on the activity of the antimicrobial organisms Staphylococcus aureus substance. Heat treatment at 100° C. for 10 minutes caused a slight reduction of activity and 121°C. for 15 minutes caused 10 Dilution a substantial reduction (table 8). Enzyme treatment x 2 x 4 x 8 x 16 x 32 x 64 Water Alcali and alcalase ------TABLE 8 Alcali ------No inoculum Development of turbidity in serial dilutions of heat treated aqueous phase 15 from C. finnarchicus (catch 2), after inoculation with the test organisms StaphyloCoCCus aureus. 1 ml of the aqueous phase from catch 2 was added 0.1 ml Dilution 0.5% (w/v) Proteinase K(Merck 1.24568.01.00) in water. The reaction mixture (pH 6.5) was incubated at 37°C. for 4 hours Heat treatment x 2 x 4 x 8 x 16 x 32 x 64 Water with occasional stirring. As a control. 1 ml of the aqueous No heating -- -- phase (pH 6.5) was incubated similarly after addition of 0.1 10 minutes 70° C. -- -- ml water without Proteinase K. The results of the BTD test 10 minutes 100° C. ------15 minutes. 121°C. ------(table 11) show that the antimicrobial substance was not No inoculum inactivated by Proteinase K treatment. Therefore, the active 25 one or more antimicrobial compounds in the C finnarchicus composition is probably not a protein. Example 6 TABLE 11 Resistance to Proteolytic Enzymes 30 Development of turbidity in serial dilutions of Proteinase K treated aqueous phase from C. finnarchicus (catch 2), after inoculation with The resistance of the antimicrobial composition to diges the test organisms Staphylococcus aureus tion by three proteolytic enzymes, pepsin, alcalase and pro Dilution teinase K was tested by the BTD method using S. aureus as a test organism. 35 Enzyme treatment x 2 x 4 x 8 x 16 x 32 x 64 Water 1 ml of the aqueous phase from catch 2 was added to 0.2 ml Proteinase Kin -- -- 1.0N HCl and 0.1 ml 0.1 NHCl with 1% (w/v) pepsin (article Water Water no. 1.07190.01.00, Merck). The reaction mixture (pH 2.36) No inoculum was incubated at 37°C. for 18 hours with occasional stirring. As a control. 1 ml of the aqueous phase was incubated simi 40 larly after addition of the same amount of acid without pepsin. The results of the BTD test (table 9) show that the antimicro Example 7 bial Substance was not inactivated by pepsin treatment. Estimation of Molecular Size of the Antimicrobial Therefore, the active one or more antimicrobial compounds 45 in the C. finnarchicus composition is probably not a protein. Substance Molecular size of the antimicrobial substance, i.e. the size TABLE 9 of the one or more antimicrobial compounds comprised Development of turbidity in serial dilutions of pepsin treated aqueous within the antimicrobial composition of the present inven phase from C. finmarchicus (catch 2), after inoculation with the test 50 tion, was estimated by processing the aqueous phase through organisms Staphylococcus aureus centrifugal filter devices (Pall Corporation) with MWCO (molecular weight cut off) of 30, 3 and 1 kDa. The results of Dilution the BTD test (table 12) indicate that the molecular weight of Enzyme treatment x 2 x 4 x 8. x 16 x 32 x 64 Water 55 the antimicrobial Substance is equal to, or less than 1 kDa. Acid and pepsin ------Acid TABLE 12 No inoculum Development of turbidity in serial dilutions of aqueous phase from C. finnarchicus (catch 2), before and after processing through 1 ml of the aqueous phase from catch 2 was added 0.3 ml 60 centrifugal filter devices with different molecular weight cut off limits. 0.1 NNaOH to obtain pH 8.0 and then added 0.2 ml 1% (w/v) Test organism was StaphyloCOCCus aureus alcalase 2.4 (Novozymes) adjusted to pH 8.0. The reaction Dilution mixture (pH 8.0) was incubated at 54° C. for 4 hours with occasional stirring. As a control. 1 ml of the aqueous phase Fraction tested x 2 x 4 x 8 x 16 x 32 x 64 Water was incubated similarly after addition of the same amount of 65 Aqueous phase ------alcali without alcalase. The results of the BTD test (table 10) Filtrate, 30 kDa ------show that the antimicrobial substance was not inactivated by US 8,647,676 B2 69 70 TABLE 12-continued the test system. C. hyperboreus was caught in the Norwegian Sea on May 15, 2006. Antimicrobial activity was not detected Development of turbidity in serial dilutions of aqueous phase from in the aqueous phase from C. hyperboreus. C. finnarchicus (catch 2), before and after processing through centrifugal filter devices with different molecular weight cut off limits. Test organism was Staphylococcus aureus 5 TABLE 1.4 Dilution Comparison of antimicrobial activity in C. hyperboretis and C. finnarchicus Fraction tested x 2 x 4 x 8 x 16 x 32 x 64 Water Dilution Filtrate, 3 kDa ------10 Filtrate, 1 kDa ------Sample x 2 x 4 x 8 x 16 x 32 x 64 x 128 x 256 Water No inoculum C. ------hyperboretis Aqueous Example 8 15 phase C. -- -- finmarchicus Type of Action Methanol extract There are three types of action of antimicrobial agents: i) static action where growth is inhibited, ii) cidal action where +: turbidity, organisms are killed and iii) lytic action where organisms are -: no turbidity killed and lysed. After 24 hours incubation of the test tubes in table 7 (aque ous phase), 10 ul from each x2 dilution was transferred to Example 10 selected agar media. No colonies could be observed after 72 25 hours incubation of the agar media. Consequently, an initial Comparison of BTD and Agar Diffusion Assay cell concentration of approximately 10 E7 per ml was reduced to less than 10 E2 per ml, corresponding to 5 LOG cycles reduction. The type of action is therefore cidic or lytic. Antimicrobial activity in the aqueous or water phase from To determine whether the type of action is cidic or lytic, 30 C. finmarchicus, was easily detected using the BTD (Broth exponential phase cultures of Escherichia coli, Salmonella Tube Dilution) method. Surprisingly, the agardiffusion assay, berta, and Staphylococcus aureus in Nutrient Broth were which is frequently used for the initial screening of antimi diluted to 1.0 E7-1.0 E8 in the same medium. 1 ml methanol crobial activity, did not detect this activity. This may explain extract were added to 9 ml of each culture, immediately after why the antimicrobial activity in water phase from this organ quantification at 0 hours. Cultures were then incubated at 37° 35 ism has not been discovered earlier. C. for 96 hours. Viable cell counts were determined using 3M When the BTD method was compared to the agar diffusion Petrifilm Aerobic Count Plates while total cell counts were assay for detection of activity in the methanol extract from C. determined using a microscope and Helber counting cham finmarchicus, it appeared that the BTD method was 32-64 ber. The results depicted in table 13 show that the action is 40 times more sensitive than the agar diffusion assay. Staphyllo bacteriocidic, not bacteriolytic. coccus aureus (ATCC 25923) was used as test strain in both the Broth Tube Dilution Method and the Agar Diffusion TABLE 13 Assay. With the Agar Diffusion Well method, well diameter Development of viable cell counts and total cell counts in Nutrient was 9 mm and each well was filled with 200 ul of the extract Broth with added methanol extract (10%) from C. finnarchicus. 45 or its dilution. In the Agar Diffusion Filter disc method, 13 Test Quantification Incubation time (hours mm diameter discs (Whatman Cat. No. 2017-013) was used. Results are shown in table 15. organism method Oh 3h 24h 96h TABLE 1.5 E. coi Viable cell counts 3.2E7 7.0 E6 <1.0 E1 <1.0 E1 50 Total cell countS 6.0 E7 6.0 E7 2.0 E7 1.0 E7 Siberia Viable cell counts 3.9E7 7.0 E6 2.9 E2 <1.0 E1 Comparison of BTD and Agar Diffusion Assay for detection of Total cell countS 6.0 E7 6.0 E7 6.0 E7 1.0 E7 antimicrobial activity in methanol extract from C. Finnarchicus. S. aureus Viable cell counts 1.5 E7 7.4 E6 2.OES <1.0 E1 Test Total cell countS 6.0 E7 4.0 E7 4.0 E7 4.0 E7 Organ- Dilutior 55 ism O x2 x 4 x 8 x 16 x 32 x 64 x 128 x 256 Water

Example 9 Broth -- -- Tube Investigation of Antimicrobial Activity in C. Dilution Agar 13 10 S O O O O O O O hyperboreus 60 Diffu sion Antimicrobial activity was not detected in the aqueous Assay, phase from another copepod species, C. hyperboreus. We method Aqueous phase prepared from a frozen sample of C. hyper Agar 4 1 O O O O O O O O boreus was tested against S. aureus (ATCC 25923). A metha 65 Diffu nol extract of C. finmarchicus with known activity was tested sion simultaneously against the same test organism as a control on US 8,647,676 B2 71 72 TABLE 15-continued TABLE 16

Comparison of BTD and Agar Diffusion Assay for detection of Antifungal activity of methanol extract antimicrobial activity in methanol extract from C. finmarchicus. Test Dilution

Test organism x 2 x 4 x 8 x 16 x 32 x 64 x 128 x 256 Water Organ- Dilutior C. albicans ------ism O x2 x 4 x 8 x 16 x 32 x 64 x 128 x 256 Water (ATCC 10 10231) S. cerevisiae ------Assay, A. niger ------Filter (ATCC disc 16404) method S. airetts -- -- 15 (ATCC +: turbidity, 25923) No inoculum - - - -: no turbidity, For the Agar Diffusion Assay, activity is expressed by inhibition zone width (mm). +: turbidity, -: no turbidity The agar diffusion assay is a technique for quantifying the ability of antimicrobial agents to inhibit bacterial growth. It has a number of variations, including the well method and the Example 12 filter disc method. Interpretation of the results from this assay relies on mathematical models, based on the assumption that the agents diffuse freely in the solid nutrient medium. The 25 Effect on Resistant Bacterial Strains technique is commonly used for determination of MIC values (Minimal Inhibitory Concentration) in solid media, such as The methanol extract was tested against meticillin-resis Nutrient Agar. Solutions of antimicrobial agents at different tant S. aureus (ATCC 43300) and multiresistant clinical iso concentrations are applied to wells punched into agar or to 30 lates of P aeruginosa, Klebsiella pneumoniae and Acineto paper discs placed on the Surface of or plates seeded with the bacter. All the isolates were strongly inhibited. S. aureus test microbial strains. Diffusion from the sources into the agar (ATCC 25923) was included in the study as a positive control. leads to growth inhibition in the vicinity of the source and to Results are shown in table 17. TABLE 17 Antibiotic effect against resistant bacteria Dilution

Test organism x 2 x 4 x 8 x 16 x 32 x 64 x 128 x 2S6 Water MRSA (ATCC 43300) -- Paeruginosa K. pneumoniae Acinetobacter S. aureus (ATCC 25923) No inoculum +: turbidity, -: no turbidity the formation of clear Zones without bacterial growth. The 50 Methicillin Resistant Staphylococcus aureus (MRSA) Zone diameter corresponds to the concentration of the anti (ATCC 43300) microbial agent. The strain is resistant to all f-lactam antibiotics. The treat ment of MRSA is therefore difficult. The strain can cause both local and systemic infections. Example 11 Klebsiella pneumoniae, Multiresistant Clinical Isolate (Ref. 55 No.: HUS11090921/08) The strain has a plasmid-mediated, broad spectrum B-lac Antifungal Activity of Methanol Extract tamase (Klebsiella Pneumoniae Carbapenemase (KPC) and is resistant to all clinical relevant B-lactam antibiotics. Fur A mould species, Aspergillus niger (ATCC 16404), was thermore, it is in vitro resistant to many other non B-lactam 60 antibiotics. Infections with such microbes are difficult to treat inhibited by the aqueous phase from C. finnarchicus (data not with available antibiotics. K. pneumoniae is a common cause shown). of urinary tract infections, but can also cause systemic infec The methanol extract was tested against two yeast species; tions. Saccharomyces cerevisiae and Candida albicans and one Pseudomonas aeruginosa, Multiresistant Clinical Isolate mould species; Aspergillus niger. C. albicans is the least 65 (Ref. No.: HUS10210891/07) Susceptible of the organisms tested. S. aureus was included as P. aeruginosa is naturally resistant to a range of different a control. Results are shown in table 16. antibiotics, and the spectre of efficientagents is narrow. Addi US 8,647,676 B2 73 74 tionally, it has a high ability to develop resistance to new Wash, elute 1 (intermediate polarity) and elute 2 (low polar antibiotics. The actual strain is in vitro resistant to, or has ity). The fractions were evaporated and tested for bioactivity reduced Susceptibility to antimicrobial agents commonly used in the treatment of P. aeruginosa infections. Severe TABLE 20 infections with P aeruginosa occur with immune deficient patients and with weak, hospitalized patients. Bioactivity in the reversed phase SPE fractions. Acinetobacter, Multiresistant Clinical Isolate (Ref. No.: HUS1123285.1/08) Fraction MIC Acinetobacter is naturally resistant to a range of different antibiotics, and the spectre of efficient agents is narrow. With 10 Wash 32 one exception, the actual isolate in vitro resistant to, or have Elute 1 16 reduced Susceptibility to all antimicrobial agents used for Elute 2 2 treatment of Acinetobacter infections. Severe infections with Acinetobacter occur with immune deficient patients and with 15 The bioactive compound(s) is probably polar or charged weak, hospitalized patients. since it was found in the aqueous fraction from the Wessel Example 13 Flügge extraction as well as the wash fraction in the reversed phase extraction. It is not likely to be a strong anionic com Further Extraction and Analysis of the Methanol pound since it failed to bind to the anionic Solid phase car Extract tridge. Anion exchange solid phase extraction was used as sample preparation prior to HPLC since all the activity eluted Sample Preparations in one fraction. Three different sample preparations were tested. This was HPLC done to find the best preparation prior to HPLC, i.e. the method that had best recovery, and at the same time rendered 25 Our first attempt was conventional reversed phase chroma a fraction that was pure enough to be loaded onto an HPLC tography. The active fraction (wash) from the anion exchange column. extraction was dried and dissolved in water and injected onto 1: Wessel-Flügge Extraction. a C18 column (250x4.6 mm). The gradient was from 96% The extract was dissolved in water and methanol, added water to 100% acetonitrile as shown in FIG. 3 (green line). chloroform and vortexed. The result is three fractions; water 30 One-minute fractions were collected, evaporated and dis methanol, methanol-chloroform and the precipitate. All frac solved to the sample volume, and tested for bioactivity. tions were evaporated and tested for activity. The activity is measured as the MIC as described in example 2. TABLE 21 Bioactivity of the analytical reversed phase HPLC fractions. TABLE 18 35 Fraction MIC Bioactivity in the Wessel-Filigge fractions. 2 O Fraction MIC 3 O 4 16 Water-methanol 32 40 5 8 Methanol-chloroform 2 6 4 Precipitate O 7 O 8 O 2: Solid Phase Extraction (SPE), Anion Exchange. Later fractions had no bioactivity The cartridge (Sep-Pak plus QMA, Waters corp.) was first 45 wetted with methanol, and then equilibrated with water. The Comparison of Chromatography with or without Polar End extract was loaded and the cartridge was washed with water, capping and finally with methanol to elute polar and weak anionic The bioactivity data in Table 21 and the corresponding compounds. Two fractions: Water wash and methanol elute. chromatogram (FIG. 3) Suggest that the bioactivity is too The fractions were evaporated, dissolved in a volume of water 50 corresponding to the sample load volume, and tested for polar to be separated by conventional reversed phase chro bioactivity. matography. The active fractions were re-chromatographed under identical conditions, or with a column with polar end TABLE 19 capping (Aquasil, Hypersil). The latter column is Suitable for 55 isolation of polar or charged compounds. This column gave Bioactivity in the anion exchange SPE fractions. better separation of the active fraction (Fraction 4, FIG. 4). However, the Aquasil-column was too small to make frac Fraction MIC tions for bioactivity testing. Up-scaling to a semi-preparative Wash 64 Methanol elute O Aquasil column failed. 60 Semi-Preparative Reversed-Phase HPLC: 3: Solid Phase Extraction, Reversed Phase. The extract from the anion exchange SPE was loaded onto The cartridge (Sep-Pak plus C18, Waters corp.) was first a semi-preparative C18 column and eluted with a gradient wetted with acetonitrile, and then equilibrated with water. with increasing acetonitrile. Fractions were collected and The extract was loaded onto the cartridge, and the cartridge 65 tested for bioactivity. As shown in Table 22, the bioactivity was washed with water, then with 40% acetonitrile and 100% eluted early. The active fraction was used for further experi acetonitrile to elute non-polar compounds. Three fractions: ments in purification. US 8,647,676 B2 75 76 TABLE 22 amount of an extract obtained from the copepod Calanus finmarchicus, thereby inhibiting bacterial growth and/or kill Bioactivity of the Semi-preparative fractions. ing said bacteria. 2. The method according to claim 1, wherein said antibac Fraction Retention time MIC terial composition is selected from the group consisting of a 2 0-5.3 16 preservative, an antiseptic, a disinfectant, an anti-fouling 3 5.3-7.2 4 4 10.8-134 O agent and a medicament. 5 18.1-193 O 3. The method according to claim 2, wherein said antibac 6 19.4-21.6 O terial composition is a preservative in a food product, feed 7 216-23.3 O 10 composition, beverage, cosmetics or pharmaceuticals. 8 23.3-25.1 O 4. The method according to claim 1, wherein the bacteria are selected from the genera of the group consisting of Normal-Phase HPLC. Pseudomonas, Enterococcus, Listeria, Bacillus, Staphyllo The active fraction from the semi-preparative reversed coccus, Escherichia, Salmonella, and Clostridium. phase chromatography (FIG. 5 and table 22) was loaded onto 15 5. The method according to claim 1, wherein the bacteria an analytical normal phase column under isocratic mode. As are selected from the group consisting of Pseudomonas mobile phase, six different ratios of ethyl acetate (EtOAc) and aeruginosa, Enterococcus faecalis, Listeria monocytogenes, methanol (MeOH) was tried: 1/99: 5/95; 10/90; 20/80:40/60 Bacillus cereus, Staphylococcus aureus, Escherichia coli, (EtOAc/MeOH, v/v %). Salmonella berta, Clostridium perfingens and Clostridium This turned out to be a promising method, and another run bifermentans. with more material was performed. One-minute fractions 6. A method for treatment of a bacterial infection in an were collected and tested for bioactivity. individual in need thereof comprising the step of administer ing to the individual a composition comprising a therapeuti TABLE 23 cally effective amount of an extract obtained from the cope 25 pod Calanus finnarchicus. Bioactivity of the normal phase fractions. 7. The method according to claim 6, wherein said treatment is ameliorating or prophylactic. Fraction MIC 8. The method according to claim 6, wherein said compo sition is an antibiotic. 30 9. The method according to claim 6, wherein said microbial infection is caused by one or more resistant bacteria with resistance to one or more antibiotics. 10. The method according to claim 6, wherein said bacte rium is selected from the group consisting of a methicillin Mass Spectrometric Analyses of the Active Peak. 35 resistant Staphylococcus aureus, a multiresistant Pseudomo The experiment described in the previous paragraph was nas aeruginosa, a multiresistant Klebsiella pneumoniae, and repeated and fraction 4 was analysed by a Q-trap mass spec a multiresistant Acinetobacter: trometer (direct infusion). Two peaks stood out from the 11. The method according to claim 6, wherein said indi background (m/z 347 and 245). These were further frag vidual is a human being. mented, but no certain conclusions can be drawn based on 40 12. The method according to claim 6, wherein said indi these data. vidual is infected with one or more pathogenic bacteria. A search on various databases on natural compounds with 13. The method according to claim 6, wherein said indi mass=346 Da (corresponding to m/z 347), returned a hit on vidual is infected with one or more pathogenic bacteria resis penostatin depicted in FIG. 12 (Iwamoto et al. Tetrahedron, tant to one or more antibiotics. 1999 vol. 55 p. 14353). This is a mild cytotoxic compound 45 14. The method according to claim 6, wherein said com that was isolated from a fungus that grows on the green algae position is administered to an individual in need thereof by Enteromorpha intestinalis. The UV-spectra of this and related topical, enteral or parenteral administration. compounds are similar to that of the active fraction from the 15. The method according to claim 6, wherein said com normal phase purification (FIG. 8). position is co-administered with one or more additional The invention claimed is: 50 drugs. 1. A method for the inhibition ofbacterial growth and/or for 16. The method according to claim 15, wherein said one or the killing of bacteria in a product, comprising the step of more additional drugs comprise one or more antibiotics. adding to the product a composition comprising an effective k k k k k