Mini Review Nov Appro Drug Des Dev Volume 2 Issue 4 - August 2017 Copyright © All rights are reserved by Asit Kumar Chakraborty DOI: 10.19080/NAPDD.2017.02.555592 Enzybiotics, A New Class of Enzyme Antimicrobials Targeted against Multidrug-Resistant Superbugs Asit Kumar Chakraborty* Department of Biochemistry and Biotechnology, Vidyasagar University, India Submission: August 07, 2017; Published: August 30, 2017 *Corresponding author: Asit Kumar Chakraborty, Department of Biochemistry and Biotechnology, OIST, Vidyasagar University, West Bengal, Midnapore 721102, India, Tel: ; Email: Abstract Gut microbiota with 2X1012 bacterial populations is essential for synthesis of vitamins, coenzymes and many other biomolecules in human and animal. But high dose of antibiotics destructed (since 1928) such bacteria in the alimentary tract posing a threat to extinct of human life. As a result signalling from human and bacteria orchestrated to build a defence to protect symbiotic relations saving both life forms. Bacteria synthesized hundreds of new genes (MDR Genes) to destroy antibiotics in different modes of actions. G-20 leaders and scientists have vowed a strong action plans (as assembled recently in Germany) to abolish the horror of superbugs which are claiming millions of death worldwide. Enzymes as therapeutic antibiotics has taken as emerging new antimicrobials derived from bacteriophages as well as bacteria like Staphylococcus sp., Streptococcus sp. and Histeria monocytogenes. Simply, autolysins, lysozymes, lysins and bacteriocins and genetic engineering principles to overcome the antibiotic resistance. GMEnzy database has built for researchers and is available at http:// biotechlab.fudan.edu.cn/database/gmenzy/.are great enzybiotics. Genetically modified enzybiotic (GMEnzy) has now a new field of enzyme antibiotic production using molecular biology Introduction The term enzibiotic was coined from two words, enzyme macAB, norA, mdtA etc.) are wide spread in conjugative plasmids and antibiotic and usually refers as the bacteriophage enzymes etc) and drug efflux genes (tetA, acrAB-TolC, mexAB-oprM, mcr, and chromosomes of superbugs which are also found in rain, sea that attack the cell wall of bacteria with lyses [1]. However, and river water posing a threat to global peoples [6]. enzybiotic present in bacteria, bacteria infected phages and in had used 80 years with success to eradicate pathogenic bacteria clinical trial in many research foundations. If enzybiotic is body fluids like tears, saliva and animal mucous [2]. Antibiotics Thus a new field of science is enzybiotics which is under like Escherichia, Klebsiella, Salmonella, Mycobacterium, injected into patient with success then all physicians believe that Pseudomonas and Vibrio species. However, last two decades such single enzyme or chimera enzyme would be most useful gradual increase of clinical isolates had shown with >95% now in superbug cure [7]. It is to save gut microbiota that provide ampicillin and amoxicillin resistant which was controlled by life saving coenzymes involved in glycosysis, TCA cycle and ATP synthesis of new derivatives of penicillin like cephalosporin generation [5]. and carbapenem drugs [3]. In 2009 NDM-1 Escherichia coli was Result found however, resistant to all class of penicillins including Beta-lactamase inhibitors like cavulinate and sulbactam but Some important enzybiotics are: avibactam [4]. Skin infections by MRSA Staphylococcus aureus, PDR nosocomial infections by Pseudomonas aeroginosa and Bacillus anthracis (Figure 1) [8]. XDR tuberculosis by Mycobacterium tuberculosis are now serious (a) Lysins. PlyG is Phage-γ amidase which can destroy threat to human and alternative approaches should be needed (b) Bacteriocins. Lysostaphin is Streptococcus simulans to overcome such crisis [5]. MDR genes (blaTEM, amp, blaNDM, enzyme that acts as endopeptidase on Staphylococcus aureus blaOXA, sul1/2, catB3, aacA4, aacC2, aph, aad, dhfr, arr3,strA/B, and many Streptococcei sp. (Figure 2) [9]. Nov Appro Drug Des Dev 2(4): NAPDD.MS.ID.555592 (2017) 001 Novel Approaches in Drug Designing & Development Figure 1: Primary amino acid sequence of lysins/holins muramidase. Figure 2: Primary amino acid sequence of a bacteriocin/HlyD type. Figure 3: Primary amino acid sequence of a Staphylococcus aureus autolysin. (c) Autolysins. S. equidermis (d) Lysozymes. Egg white lysozyme is muramidase that >4) glycoside bong between N-acetyl glucosamine and N-acetyl destroy peptidoglycans and very effective against Gram (+) autolysin enzyme lyses β (1- muraminic acid of many bacteria (Figure 3) [10]. bacteria [11]. How to cite this article: Chakraborty AK. Enzybiotics, A New Class of Enzyme Antimicrobials Targeted against Multidrug-Resistant Superbugs. Nov Appro 002 Drug Des Dev. 2017; 2(4) : 555592. DOI: 10.19080/NAPDD.2017.02.555592. Novel Approaches in Drug Designing & Development The lysins are 453-473aa long extracellular enzymes and 7. Thallinger B, Prasetyo EN, Nyanhongo GS, Guebitz GM (2013) have been sequenced from Streptococcus suis, Streptococcus agalactiae and others (protein ids. WP_061713285, Antimicrobial enzymes: an emerging strategy to fight microbes and WP_043026720, WP_070043600) with 50-150 mutations 8. microbialYang H, Zhang biofilms. Y, YuBiotechnol J, Huang J 8(1):Y, Zhang 97-109. XE, et al. (2014) A novel chimeric lysine with high antimicrobial activity against methicillin- among themselves [12,13]. The multispecies bacteriocin (protein resistant Staphylococcus aureus in vitro and in vivo. Antimicrob Agents id. WP_013103375) has only 54% amino acid similarities to Chemother. 58(1): 536-542. the Leuconostoc sp. Bacteriocin secretory protein (protein id. 9. Manoharadas S, Witte A, Bläsi U (2009) Antimicrobial activity of WP_030058663) but further pharmacological data are lacking. chimeric enzybiotic towards S. Aureus. J Biotechnol 139(1): 118-128. Autolysins are also much diverged as S. aureus enzyme (protein 10. Hermoso JA, García JL, García P (2007) Taking aim on bacterial id. AAA99982; accession no. L41499) has only 60% homology pathogens: from phage therapy to enzybiotics. Curr Opin Microbiol with 8% gap to other autolysin enzymes (protein id. BAD83399) 10(5): 461-472. [14]. Genetically recombinant Lysins have great potential in 11. Foster SJ (1995) Molecular characterization and functional analysis curing MDR-bacteria [15-18]. P2neumococcal LytA autolysin, a of the major autolysin of Staphylococcus aureus 8325/4. J Bacteriol 177(19): 5723-5725. potent therapeutic agent in peritonitis-sepsis caused by highly beta-lactamase resistant Streptococcus pneumonia [19,20]. 12. Becker SC, Foster-FJ, Donovan DM (2008) The phageK lytic enzyme LysK and lysostaphin act synergistically to kill MRSA. FEMS Microbiol Discussion Lett 287(2): 185-191. 13. Hojckova K, Stano M, Klucar L (2013) Phibiotics: Catalogue of therapeutic enzybiotics relevant research studies and practical many molecular approaches have undertaken which have applications. BMC Microbiol 13: 53. Enzybiotics is an emerging field of medicinal science with patent litigations and many data are hidden from GenBank 14. Rashel M, Uchiyama J, Ujihara T, Uehara Y, Kuramoto S, et al. (2007) database now [13]. It also has combined with phage therapy technologies targeting both Gram (+) and Gram (-) bacterial derived from bacteriophage Phi MR11. J Infect Dis 196(8): 1237-1247. Efficent elimination of multidrug-resistant S. aureus by cloned Lysin pathogenesis originating from MDR genes of superbugs [10]. 15. Veiga-CP, Ageitos JM, Poza M, Villa TG (2007) Enzybiotics: a look to the We believe as MDR genes are created both from human and future, Recalling the past. J Pharm Sci 96(8): 1917-1924. bacteria symbiosis, it will be there with gut microbiota [5]. So 16. Nelson DC, Schmelcher M, Rodriguez-RL, Klumpp J, Pritchard DG, et al. to eliminate the pathogenic bacteria alternative to antibiotics (2012) Endolysins as antibacterials. Adv Virus Res 83: 299-365. will be forthcoming like gene medicines (antisense, Casper-Cas, 17. Yokoi KJ, Kawahigashi N, Uchida M, Sugahara K, Shinohara M, et al. SiRNA, miRNA, ribozyme) and nanodrug-carriers [21]. Thus (2005) The two-component cell lysis genes holWMY and lysWMY of enzybiotic is in good place in molecular medicine and its success the Staphylococcus warneri M phage varphiWMY: cloning, sequencing, expression, and mutational analysis in Escherichia coli. Gene 351: 97- is ahead. Novel chimerical endolysins with broad antimicrobial 108. activity against methicillin-resistant Staphylococcus aureus was 18. Fenton M, Ross P, McAuliffe O, O Mahony J, Coffey A (2010) Recombinant reported [16,22]. About 1144 enzybiotics along with 216 natural bacteriophage Lysins as antibacterials. Bioeng Bugs 1(1): 9-16. resources (heterogeneous phyto-antibiotics) have been listed in 19. Maestro B, Sanz JM (2016) Choline binding proteins from Streptococcus GMEnzy database [2,13,23,24]. pneumoniae: A dual role as enzybiotics and targets for the design of new antimicrobials. Antibiotics (Basel) 5(2): 21. References 20. Rodríguez-CV, García P, Huelves L, García E, Del Prado G, et al. (2007) 1. Borysowaski J, Gorski A (2010) Enzybiotics and their potential Pneumococcal LytA autolysin, a potent therapeutic agent in peritonitis- application in medicine. In: Villa Tg, Veiga Crespo P (Eds.), Enzybiotics: sepsis caused by highly brta-lactamase resistant Streptococcus antibiotic enzymes as drugs and therapeutics. (11th edn), John Wiley & pneumonia. Antimicrob Agents Chemother 51(9): 3371-3373. Sons Inc.