Review Articles

Antimicrobial properties of the skin secretions of frogs

Thashlin Govender, Abeda Dawood, Adriaan J. Esterhuyse, David R. Katerere
South African Journal of Science | Vol 108, No 5/6 | a795 | DOI: | © 2012 Thashlin Govender, Abeda Dawood, Adriaan J. Esterhuyse, David R. Katerere | This work is licensed under CC Attribution 4.0
Submitted: 08 June 2011 | Published: 16 May 2012

About the author(s)

Thashlin Govender, Department of Biomedical Technology, Cape Peninsula University of Technology, Cape Town, South Africa
Abeda Dawood, National Zoological Gardens, Pretoria, South Africa
Adriaan J. Esterhuyse, Department of Biomedical Technology, Cape Peninsula University of Technology, Cape Town, South Africa
David R. Katerere, PROMEC Unit, Medical Research Council, Cape Town, South Africa


Antimicrobial resistance results in increased morbidity and mortality, and increased health-care costs. Therefore the need to develop new classes of antibiotics is indispensable. Antimicrobial peptides are a relatively new class of potential antibiotics which are fast acting, possess broad-spectrum activity and are able to escape many of the currently known mechanisms of drug resistance. They have been shown to be active against Gram-negative and Gram-positive bacteria, fungi, enveloped viruses and even cancer cells. However, toxicity to healthy host cells remains a concern and has affected the clinical development of therapeutics based on antimicrobial peptides. The purpose of this review is to discuss recent advances in research focused on antimicrobial peptides from frogs and the challenges in conducting research in this area in southern Africa. An extensive literature review of relevant articles published between 1980 and the present was conducted using PubMed, ScienceDirect, Sabinet, Elsevier and GoogleScholar. There has been little research done on anurans from southern Africa which are endemic to the region, and there is therefore a need to focus on this group for the purposes of bioprospecting for potentially new antimicrobial peptide compounds.


anuran; Southern Africa; frog secretions; antimicrobial peptides; bioprospecting


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Levy S. Antibiotic resistance: Origins, evolution, selection, and spread. New York: John Wiley; 1997.

Chicarelli-Robinson M, Gibbons S, McNicholas C. Plants and microbes as complementary sources of chemical diversity for drug discovery. In: Wrigley S, Hayes M, Thomas R, Chrystal E, eds. Phytochemical diversity: A source of new industrial products. London: Royal Society of Chemistry, 1997; p. 57–83.

Georgopapadakou NH, Walsh TJ. Antifungal agents: Chemotherapeutic targets and immunologic strategies. Antimicrob Agents Chemother. 1996;40(2):279–291.

Walsh C, Wright G. Introduction: Antibiotic resistance. Chem Rev. 2005;105(2):391–394., PMid:15700949

Harris A, Torres-Viera C, Venkataraman L, DeGirolami P, Samore M, Carmeli Y. Epidemiology and clinical outcomes of patients with multiresistant Pseudomonas aeruginosa. Clin Infect Dis. 1999;28:1128–1133.

World Health Organization (WHO). The world health report 2000: Life in the 21st century. A vision for all. Geneva: WHO; 2000.

Angeletti L, Agrimi U, Curia C, French D, Mariani-Costantini R. Healing rituals and sacred serpents. Lancet. 1992;340:223–225.

Hancock R, Patrzykat A. Clinical development of cationic antimicrobial peptides: From natural to novel antibiotics. Curr Drug Targets Infect Disord. 2002;2:79–83.

Costa-Neto E. Healing with animals in Feira de Santana City, Bahia, Brazil. J Ethnopharmacol. 1998;65:225–230.

Amato I. From ‘hunter magic’, a pharmacopoeia? Science. 1992;258:1306., PMid:1455225

Purna Sai K, Neelakanta P, Babu R, Babu M. Investigation on wound healing by using amphibian skin. Indian J Exp Biol. 1995;33:673–676. PMid:8557310

Erspamer V, Erspamer GF, Severini C, et al. Pharmacological studies of ‘sapo’ from the frog Phyllomedusa bicolor skin: A drug used by the Peruvian Matses Indians in shamanic hunting practices. Toxicon. 1993;31(9):1099–1111.

Le TT. Vietnamese experience in the treatment of burns. Hanoi: Gioi Publishers; 1992.

Underhill R. Laboratory anatomy of the frog. 5th ed. Dubuque, IA: Wm. C. Brown; 1988.

Passmore N, Carruthers V. South African frogs. Johannesburg: Witwatersrand University Press; 1979.

Wager V. Frogs of South Africa: Their fascinating life stories. Johannesburg: Delta; 1986.

Minkoff E. A laboratory guide to frog anatomy. New York: Pergamon; 1975.

Channing A. Amphibians of central and southern Africa. Pretoria: Protea Bookhouse; 2006.

Kimbrell DA, Beutler B. The evolution and genetics of innate immunity. Nat Rev Genet. 2001;2(4):256–267., PMid:11283698

Barra D, Simmaco M. Amphibian skin: A promising resource for antimicrobial peptides. Tibtech. 1995;13:205–209. 1016/S0167-7799(00)88947-7

Tyler MJ, Stone DJM, Bowie JH. A novel method for the release and collection of dermal, glandular secretions from the skin of frogs. J Pharmacol Toxicol Methods. 1992;28(4):199–200.

Nicolas P, Mor A. Peptides as weapons against microorganisms in the chemical defense system of vertebrates. Annu Rev Microbiol. 1995;49:277–304., PMid:8561461

Clarke B. The natural history of amphibian skin secretions, their normal functioning and potential medical applications. Biol Rev Camb Philos Soc. 1997;72:365–379., PMid:9336100

Lazarus L, Attila M. The toad, ugly and venomous, wears yet a precious jewel in his skin. Prog Neurobiol. 1993;41:473–507. 10.1016/0301-0082(93)90027-P

Zasloff M. Magainins, a class of antimicrobial peptides from Xenopus skin: Isolation, characterisation of two active forms and partial cDNA sequence of a precursor. Proc Natl Acad Sci. 1987;84:5449–5453.

Chen H, Boman H, Morell J. Synthetic magainin analogues with improved antimicrobial activity. FEBS Lett. 1988;236:462–466. 10.1016/0014-5793(88)80077-2

Simmaco M, Mangoni M, Boman A, Barra D. Experimental infections in Rana esculenta with Aeromonas hydrophila: A molecular mechanism for the control of the natural flora. Scand J Immunol. 1998;48:357–363., PMid:9790305

Conlon J. The therapeutic potential of antimicrobial peptides from frog skin. Rev Microbiol. 2004;15:17–25.

Che Q, Zhou Y, Yang H, Li J, Xu X, Lai R. A novel antimicrobial peptide from amphibian skin secretions of Odorrana grahami. Peptides. 2008;29(4):529–535., PMid:18282640

Mangoni ML, Miele R, Renda TG, Barra D, Simmaco M. The synthesis of antimicrobial peptides in the skin of Rana esculenta is stimulated by microorganisms. FASEB J. 2001;15:1431–1432. PMid:11387247

Pal T, Abraham B, Sonnevend A, Dimitrov T, John A. Brevinin-1BYa: A naturally occurring peptide from frog skin with broad-spectrum antibacterial and antifungal properties. Int J Antimicrob Agents. 2006;27:525–529., PMid:16713189

Conlon JM, Kolodziejek J, Nowotny N. Antimicrobial peptides from ranid frogs: Taxonomic and phylogenetic markers and a potential source of new therapeutic agents. Biochim Biophys Acta. 2004;1696(1):1–14. PMid:14726199

Clark D, Durell S, Maloy W, Zasloff M. Ranalexin, a novel antimicrobial peptide from bullfrog (Rana catesbeiana) skin, structurally related to the bacterial antibiotic, polymyxin. J Biochem. 1994;269:10849–10855.

Gabay JE. Ubiquitous natural antibiotics. Science. 1994;264(5157):373–374., PMid:8153623

Kim JB, Iwamuro S, Knoop FC, Conlon JM. Antimicrobial peptides from the skin of the Japanese mountain brown frog, Rana ornativentris. J Pept Res. 2001;58(5):349–356. 00947.x, PMid:11892844

Isaacson T, Soto A, Iwamuro S, Knoop FC, Conlon JM. Antimicrobial peptides with atypical structural features from the skin of the Japanese brown frog Rana japonica. Peptides. 2002;23(3):419–425.

Conlon JM, Sonnevend A, Patel M, et al. A melittin-related peptide from the skin of the Japanese frog, Rana tagoi, with antimicrobial and cytolytic properties. Biochem Biophys Res Commun. 2003;306(2):496–500.

Che Q, Zhou Y, Yang H, Li J, Xu X, Lai R. A novel antimicrobial peptide from amphibian skin secretions of Odorrana grahami. Peptides. 2008;29:529–535., PMid:18282640

Mor A, Nguyen VH, Delfour A, Migliore-Samour D, Nicolas P. Isolation, amino acid sequence, and synthesis of dermaseptin, a novel antimicrobial peptide of amphibian skin. Biochemistry. 1991;30(36):8824–8830., PMid:1909573

Vouldoukis I, Shai Y, Nicolas P, Mor A. Broad spectrum antibiotic activity of the skin-PYY. FEBS Lett. 1996;380(3):237–240.

Basir Y, Floyd C, Dulka J, Knoop F, Conlon J. Multiple antimicrobial peptides and peptides related to bradykinin and neurmedin N isolated from skin secretions of the pickerel frog, Rana palustris. Biochim Biophys Acta. 2000;1543:95–105.

Mangoni ML, Shai Y. Temporins and their synergism against Gram-negative bacteria and in lipopolysaccharide detoxification. Biochim Biophys Acta. 2009;1788(8):1610–1619., PMid:19422786

Domanov YA, Kinnunen PKJ. Antimicrobial peptides temporins B and L induce formation of tubular lipid protrusions from supported phospholipid bilayers. Biophys J. 2006;91(12):4427–4439., PMid:16997872, PMCid:1779916

Abbassi F, Oury B, Blasco T, et al. Isolation, characterization and molecular cloning of new temporins from the skin of the North African ranid Pelophylax saharica. Peptides. 2008;29(9):1526–1533., PMid:18584916

Marenah L, Flatt PR, Orr DF, Shaw C, Abdel-Wahab YH. Skin secretions of Rana saharica frogs reveal antimicrobial peptides esculentins-1 and -1B and brevinins-1E and -2EC with novel insulin releasing activity. J Endocrinol. 2006;188(1):1–9., PMid:16394170

Wang L, Zhou M, McGrath S, et al. A family of kassinatuerin-2 related peptides from the skin secretion of the African hyperoliid frog, Kassina maculata. Peptides. 2009;30(8):1428–1433., PMid:19427345

Minter LR, Burger M, Harrison JA, Braack HH, Bishop PJ, Knoepfer D. Atlas and red data book of the frogs of South Africa, Lesotho and Swaziland. SI/MAB Series no. 9. Washington DC: Smithsonian Institution; 2004.

Bals R. Epithelial antimicrobial peptides in host defense against infection. Respir Res. 2000;1(3):141–150., PMid:11667978, PMCid:59560

Rinaldi AC. Antimicrobial peptides from amphibian skin: An expanding scenario. Curr Opin Chem Biol. 2002;6(6):799–804.

Reddy KVR, Yedery RD, Aranha C. Antimicrobial peptides: Premises and promises. Int J Antimicrob Agents. 2004;24(6):536–547., PMid:15555874

Rash LD, Morales RA, Vink S, Alewood PF. De novo sequencing of peptides from the parotid secretion of the cane toad, Bufo marinus (Rhinella marina). Toxicon. 2011;57(2):208–216., PMid:21115026

Daffre S, Bulet P, Spisni A, Ehret-Sabatier L, Rodrigues E, Travassos L. Bioactive natural peptides. Stud Nat Prod Chem. 2008;35:597–691.

Simmaco M, Mignogna G, Barra D. Antimicrobial peptides from amphibian skin: What do they tell us? Peptide Sci. 1998;47(6):435–450.<435::AID-BIP3>3.0.CO;2-8

Sitaram N, Naggaraj R. Antimicrobial peptides as novel therapeutic agents to combat drug-resistant microbial infections. Curr Med Chem. 2002;1:413–430.

Zürbig P, Mischak H. Peptidomics approach to proteomics. In: Soloviev M, Shaw C, Andrén P, eds. Peptidomics: Methods and applications. Hoboken, NJ: Wiley; 2008.

Ali MF, Lips KR, Knoop FC, Fritzsch B, Miller C, Conlon JM. Antimicrobial peptides and protease inhibitors in the skin secretions of the crawfish frog, Rana areolata. Biochim Biophys Acta. 2002;1601(1):55–63. PMid:12429503

Zasloff M. Antimicrobial peptides of multicellular organisms. Nature. 2002;415(6870):389–395., PMid:11807545

Conlon JM, Bevier CR, Coquet L, et al. Peptidomic analysis of skin secretions supports separate species status for the tailed frogs, Ascaphus truei and Ascaphus montanus. Comp Biochem Physiol Part D Genomics Proteomics. 2007;2(2):121–125., PMid:20483285

Bradbury J. Frog skin hope for HIV prevention. Drug Discovery Today. 2005;10(22):1489–1490.

Yasin B, Pang M, Turner JS, et al. Evaluation of the inactivation of infectious herpes simplex virus by host-defense peptides. Eur J Clin Microbiol Infect Dis. 2000;19(3):187–194., PMid:6756909

Haynie SL, Crum GA, Doele BA. Antimicrobial activities of amphiphilic peptides covalently bonded to a water-insoluble resin. Antimicrob Agents Chemother. 1995;39(2):301–307.

Nascimento A, Chapeauroge Preales J, Sebben A, Sousa M, Fontes W, Castro M. Purification, characterization and homology analysis of ocellatin 4, a cytolytic peptide from the skin secretion of the frog Leptodactylus ocellatus. Toxicon. 2007;50:1095–1104., PMid:17884127

Sukwon K, Myoung S, Chung J, Lim D, Byeong J. Purification and characterisation of antimicrobial peptides from the skin secretion of Rana dybowskii. Peptides. 2007;28:1532–1539., PMid:17698251

Rollins-Smith L, Reinhart L. Antimicrobial peptide defenses in amphibian skin. Integr Compar Biol. 2005;45:137–142., PMid:21676754

Pressey R, Cowling R, Rouget M. Formulating conservation targets for biodiversity pattern and process in the Cape Floristic Region, South Africa. Biol Conserv. 2003;112:99–127.

Eloff JN. A sensitive and quick microplate method to determine the minimal inhibitory concentration of plant extracts for bacteria. Planta Med. 1998;64(8):711–713., PMid:9933989

Gordon Y, Romanowski E, McDermott A. A review of antimicrobial peptides and their therapeutic potential as anti-infective drugs. Curr Eye Res. 2005;30(7):505–515., PMid:16020284, PMCid:1497874

Sengupta J, Khan MA, Huppertz B, Ghosh D. In-vitro effects of the antimicrobial peptide Ala8,13,18-magainin II amide on isolated human first trimester villous trophoblast cells. Reprod Biol Endocrinol. 2011;9:49., PMid:21496281, PMCid:3098154

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