Int.J.Curr.Microbiol.App.Sci (2015) 4(1): 310-317

ISSN: 2319-7706 Volume 4 Number 1 (2015) pp. 310-317 http://www.ijcmas.com

Review Article Cyanobacterial natural products as antimicrobial agents

V.D. Pandey*

Department of Botany, Government Post-Graduate College Rishikesh-249201(Uttarakhand), India *Corresponding author

A B S T R A C T

Cyanobacteria (blue-green algae) constitute a morphologically diverse and widely distributed group of Gram-negative photosynthetic prokaryotes. Possessing K e y w o r d s tremendous adaptability to varying environmental conditions, effective protective mechanisms against various abiotic stresses and metabolic versatility, they colonize , and grow in different types of terrestrial and aquatic habitats. In addition to the Natural potential applications of cyanobacteria in various fields, such as agriculture, products, aquaculture, pollution control, bioenergy and nutraceuticals, they produce Bioactive chemically diverse and pharmacologically important novel bioactive compounds, compounds, including antimicrobial compounds (antibacterial, antifungal and antiviral). The Pharmaceutical emergence and spread of antibiotic resistance in pathogenic microbes against compounds, commonly used antibiotics necessitated the search for new antimicrobial agents Antimicrobial from sources other than the traditional microbial sources (streptomycetes and agents, fungi). Various features of cyanobacteria, including their capability of producing antimicrobial compounds, make them suitable candidates for their exploitation as a natural source of antimicrobial agents.

Introduction

Cyanobacteria (Blue-green algae) are a attributed to their tremendous adaptability primitive, diverse and ubiquitous group of to varying environmental conditions as photosynthetic prokaryotes, exhibiting well as effective protective and tolerance resemblance with Gram-negative mechanisms against various abiotic in cellular organization and green plants in stresses (Tandeau de Marsac and oxygenic photosynthesis (Stanier and Houmard, 1993; Potts, 1999; Ehling- Cohen-Bazire, 1977). With long Schulz and Scherer, 1999). With evolutionary history, they are among the remarkable diversity in their structure, oldest life forms existing on earth. They which may be unicellular, colonial or colonize, grow and survive in almost all filamentous (branched or unbranched); kinds of terrestrial and aquatic (freshwater they include 150 genera with more than and marine) ecosystems which can be 2000 species. The presence or production of a wide array of photosynthetic

310 Int.J.Curr.Microbiol.App.Sci (2015) 4(1): 310-317 pigments, storage products, and primary products from different sources have and secondary metabolites indicates their gained importance in view of the biochemical diversity. They are considered emergence and spread of antibiotic as metabolically versatile organisms as resistance in pathogenic microbes, which well as highly productive and efficient constitutes a major and challenging public biological systems. Both ecologically and health problem, due to indiscriminate use economically, they are important or misuse of antibiotics (Trias and Gordon, organisms with varied implications and 1997; Cowan, 1999). Organisms other applications. In addition to the potential than cyanobacteria, such as streptomycetes applications of cyanobacteria in various and fungi are the source of majority of fields, such as agriculture, aquaculture, antibiotics. Photoautotrophic organisms human nutrition or nutraceuticals, like cyanobacteria have not yet received bioenergy and pollution control much attention as a source of antibiotics or (bioremediation), they are known to antimicrobial compounds. However, produce a bewildering array of novel systematic screening and phytochemical bioactive compounds with diverse investigation of cyanobacteria over the activities. Bioactive (biologically active past two decades have revealed the compounds) are the compounds/molecules production of antimicrobial compounds which at low concentrations affect a living (e.g. antibacterial, antifungal, antiviral) by organism, tissue or cell in beneficial or many species. Some antimicrobial detrimental manner or may elicit compounds are known to exhibit single pharmacological or toxicological effects in activity while others exhibit multiple humans and animals. They may be activities. The biosynthetic pathways synthetic or natural, produced by various responsible for the production of various species microbes and plants. Most of them cyanobacterial antimicrobial compounds are secondary metabolites with diverse and the factors regulating their production chemical structures. Among the known are not completely known. However, cyanobacterial bioactive compounds, certain reports indicate that the production many are pharmacologically important and of antimicrobial compounds in hold immense potential for drug cyanobacteria is regulated by culture development. These include antimicrobial conditions and nutrients (Fish and Codd, compounds, anticancerous/antineoplastic 1994; Patterson and Bolis, 1993, 1995). agents, antimitotic agents, muscle- relaxants, immunomodulatory agents and Antibacterial and antifungal agents enzyme inhibitors (Singh et al., 2005; Singh et al., 2011; Prasanna, 2010; Volk Cyanobacteria of genera and and Fulkert, 2006; Tan, 2007; Skulberg, Tolypothrix produce potent antifungal and 2000; Barrios-Llerena, 2007; Patterson et cytotoxic agents, called scytophycins, al., 1994). Bioactive compounds produced which are chemically congeneric by cyanobacteria may be released outside macrolides (Ishibashi et al., 1986; Carmeli the cells, either actively or passively or by et al., 1990). Tolytoxin (6-hydroxy-7-0- autolysis (Metting and Pyne, 1986). methyl-scytophycin b), a well characterized scytophycin, was originally Antimicrobial compounds isolated from the cyanobacterium Tolypothrix conglutinata var. colorata in Antimicrobial properties of natural 1977 (Moore, 1981). The cyanobacterial

311 Int.J.Curr.Microbiol.App.Sci (2015) 4(1): 310-317 species producing scytophycins and has been isolated from the cyanobacterium tolytoxin include Scytonema sp. (Bui et al., 2007). pseudohofmanni, S.mirabile, S. burmanicum and S. ocellatum (Ishibashi et Indole alkaloids, named as hapalindoles, al., 1986; Carmeli et al., 1990). In addition are antibacterial and antifungal agents to antifungal activity, scytophycins and produced by an edaphic cyanobacterium tolytoxin exhibit strong cytotoxicity Hapalosiphon fontinalis (Moore et al., towards cancerous cell lines (Moore et al., 1987). The Fischerella muscicola, a 1986; Patterson and Carmeli, 1992). terrestrial cyanobacterium, has been reported to produce an antifungal Various cyclic peptides and depsipeptides compound, fischerindole L, which is isolated from cyanobacteria have been chemically related to hapalindoles (Park et reported as antimicrobial agents. These al., 1992). Tubercidin and toyocamycin include tenuecyclamides (antibacterial and are fungicidal and cytotoxic nucleosides cytotoxic agent) from lithophytic produced by Plectonema radiosum and cyanobacterium Nostoc spongiaeforme Tolypothrix tenuis, respectively (Stewart et var. tenue (Banker and Carmeli, 1998), al., 1988). Ambiguine isonitriles, schizotrin A (antifungal and antibacterial exhibiting fungicidal activity, are compound) from Schizothrix sp. hapalindole-type alkaloids produced by (Pergament and Carmeli, 1994), cyanobacterial species Fischerella hormothamnins (antibacterial and ambigua, Hapalosiphon hibermicus and antifungal compounds) from the marine Westiellopsis prolifica of the family cyanobacterium Hormothamnion Stigonemataceae (Smitka et al., 1992). enteromorphoides (Gerwick et al., 1989), The antifungal compounds tjipanazoles, laxaphycins (antifungal agents) from the which are chemically indolocarbazoles, terrestrial cyanophyte Anabaena laxa have been isolated from the terrestrial (Frankmölle et al., 1992a,b), cyanobacterium Tolypothrix tjipanasensis majusculamide C (antifungal agent) from (Bonjouklian et al., 1991). Ambigols the marine cyanobacterium Lyngbya (polychlorinated aromatic compounds), majuscula (Carter et al., 1984), exhibiting antibacterial and antifungal kawaguchipeptin B (antibacterial agent) activities, are produced by the terrestrial from the toxic cyanobacterium Microcystis cyanobacterium Fischerella ambigua aeruginosa (Ishida et al., 1997), (Falch et al., 1993). calophycin (fungicide) from the terrestrial blue-green alga Calothrix fusca (Moon et The antibacterial oxazole peptide alkaloid, al., 1992), and tolybyssidins (antifungal named as muscoride A, is produced by the compounds) from the epilithic fresh water cyanobacterium Nostoc cyanobacterium Tolypothrix byssoidea muscorum (Nagatsu et al., 1995). (Jaki et al., 2001). Malyngamides, amides of the fatty acid (&) -7(S)-methoxytetradec-4(E)-enoate, The cyanobacterium Nostoc commune are antibacterial agents isolated from the produces a novel antibacterial compound, marine cyanobacterium Lyngbya called noscomin, which is a diterpenoid majuscula (Gerwick et al., 1987). (Jaki et al., 1999). Carbamidocyclophanes Tanikolide, an antifungal lactone, is A-E (chlorinated paracyclophanes), another antimicrobial compound isolated exhibiting antibiotic and cytotoxic activity, from L. majuscula (Singh et al., 1999).

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Antiviral agents cytomegalovirus (Hayashi et al., 1996a,b). Ca-SP selectively inhibits the penetration With the aim of discovering new antiviral of virus into host cells. agents, extracts of various cyanobacterial species were screened against human Cyanobacteria have been recognized as a pathogenic viruses, including HIV promising and prodigious source of novel (Knübel et al., 1990; Gustafson et al., pharmaceutical compounds of various 1989). The sulfoglycolipids isolated from types. The development of resistance in cyanobacteria have been reported to pathogenic microorganisms against inhibit the activity of reverse transcriptase commonly used antibiotics made of human immunodeficiency virus (HIV) imperative to look for new antimicrobial (Loya et al., 1998). Cyanovirin-N, a agents from natural sources other than the carbohydrate binding protein, isolated traditional microorganisms. Interestingly, from the cyanobacterium Nostoc the production of antimicrobial ellipsosporum, exhibits potent anti-HIV compounds by various species of activity (Boyd et al., 1997; Botos and cyanobacteria opens up new possibilities Wlodawer, 2003). It binds to viral surface for the exploitation of these organisms as envelope glycoprotein gp120, interfering potential source of antimicrobial agents or with the fusion of HIV with the cellular antibiotics. The desired features, such as receptor CD4. Bokesch et al. (2003) rapid growth rate, simple growth isolated a potent novel anti-HIV protein, requirements, and amenability to , from aqueous extracts of the controlled laboratory culture, ubiquity and cultured cyanobacterium Scytonema easy accessibility make cyanobacteria varium that acts by binding to viral coat suitable candidates for their use and proteins gp120, gp160 and gp41 (Bokesch exploitation as a natural source of et al., 2003). The terrestrial antimicrobial agents and other cyanobacterium Nostoc flagelliforme is pharmaceutical compounds. Additionally, known to produce an antiviral acidic because of their antimicrobial polysaccharide, nostoflan, exhibiting compounds/activities, they would be potent activity against HSV-1 (herpes suitable biocontrol agents for simplex virus type-1), HSV-2, human phytopathogenic bacteria and fungi. The cytomegalovirus and influenza A virus potential of cyanobacteria in (Kanekiyo et al., 2005, 2007, Hayashi et pharmaceuticals has yet to be fully al., 2008). Cyclic depsipeptides, realized. Increased research efforts ichthyopeptins A and B, isolated from the towards extensive screening, purification cyanobacterium Microcystis ichthyoblabe, and characterization of antimicrobial possess antiviral activity against influenza compounds, strain improvement, genetic A virus (Zainuddin et al., 2007). Calcium manipulation, metabolic engineering, spirulan (Ca-SP), a natural sulfated optimization of growth media and culture polysaccharide, isolated from Spirulina conditions, and high density culture are platensis, has been reported to exhibit needed. Ecologically, the production of antiviral activity against various enveloped antimicrobial compounds by cyanobacteria viruses, such as human immunodeficiency is important because of their possible role virus type-1 (HIV-1), herpes simplex virus in chemical interactions that occur in type-1 (HSV-1), measles virus, mumps microbial communities in nature. They virus, influenza A virus and human may confer selective advantage to

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