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Vipericidins: a novel family of cathelicidin-related peptides from the venom gland of South American pit vipers

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Abstract

Cathelicidins are phylogenetically ancient, pleiotropic host defense peptides—also called antimicrobial peptides (AMPs)—expressed in numerous life forms for innate immunity. Since even the jawless hagfish expresses cathelicidins, these genetically encoded host defense peptides are at least 400 million years old. More recently, cathelicidins with varying antipathogenic activities and cytotoxicities were discovered in the venoms of poisonous snakes; for these creatures, cathelicidins may also serve as weapons against prey and predators, as well as for innate immunity. We report herein the expression of orthologous cathelicidin genes in the venoms of four different South American pit vipers (Bothrops atrox, Bothrops lutzi, Crotalus durissus terrificus, and Lachesis muta rhombeata)—distant relatives of Asian cobras and kraits, previously shown to express cathelicidins—and an elapid, Pseudonaja textilis. We identified six novel, genetically encoded peptides: four from pit vipers, collectively named vipericidins, and two from the elapid. These new venom-derived cathelicidins exhibited potent killing activity against a number of bacterial strains (S. pyogenes, A. baumannii, E. faecalis, S. aureus, E. coli, K. pneumoniae, and P. aeruginosa), mostly with relatively less potent hemolysis, indicating their possible usefulness as lead structures for the development of new anti-infective agents. It is worth noting that these South American snake venom peptides are comparable in cytotoxicity (e.g., hemolysis) to human cathelicidin LL-37, and much lower than other membrane-active peptides such as mastoparan 7 and melittin from bee venom. Overall, the excellent bactericidal profile of vipericidins suggests they are a promising template for the development of broad-spectrum peptide antibiotics.

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Acknowledgments

Research at Federal University of Ceará supported by the Brazilian National Council for Scientific and Technological Development (CNPq), by the Ministry of Science and Technology, and by the Coordination for the Improvement of Higher Education Personnel (CAPES). Research at Pompeu Fabra University supported by the Spanish Ministry of Science and Innovation (SAF 2011-24899) and by Generalitat de Catalunya (SGR2009-00492). Mobility support from the European Commission, Marie Curie Actions—International Research Staff Exchange Scheme (no. 247513, MEMPEPACROSS), is gratefully acknowledged.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona Biomedical Research Park, Dr. Aiguader, 80, 08003, Barcelona, Spain

    C. B. Falcao, B. G. de La Torre, C. Pérez-Peinado, D. Andreu & G. Rádis-Baptista

  2. Laboratory of Biochemistry and Biotechnoloy, Institute for Marine Sciences, Federal University of Ceará, Av. da Abolição, 3207, 60165-081, Fortaleza, CE, Brazil

    C. B. Falcao & G. Rádis-Baptista

  3. Department of Bioengineering, Stanford University, 318 Campus Drive, W300B James H. Clark Center, Stanford, CA, 94305-5444, USA

    A. E. Barron

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  1. C. B. Falcao
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  2. B. G. de La Torre
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  3. C. Pérez-Peinado
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  4. A. E. Barron
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  5. D. Andreu
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  6. G. Rádis-Baptista
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Correspondence to D. Andreu or G. Rádis-Baptista.

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Falcao, C.B., de La Torre, B.G., Pérez-Peinado, C. et al. Vipericidins: a novel family of cathelicidin-related peptides from the venom gland of South American pit vipers. Amino Acids 46, 2561–2571 (2014). https://doi.org/10.1007/s00726-014-1801-4

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  • DOI: https://doi.org/10.1007/s00726-014-1801-4

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