title: Vipericidins: a novel family of cathelicidin-related peptides from the venom gland of South American pit vipers.
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.
authors.affiliation: Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona Biomedical Research Park, Dr. Aiguader, 80, 08003, Barcelona, Spain.
authors.forename: C B
authors.initials: CB
authors.lastname: Falcao
authors.forename: B G
authors.initials: BG
authors.lastname: de La Torre
authors.forename: C
authors.initials: C
authors.lastname: Pérez-Peinado
authors.forename: A E
authors.initials: AE
authors.lastname: Barron
authors.forename: D
authors.initials: D
authors.lastname: Andreu
authors.forename: G
authors.initials: G
authors.lastname: Rádis-Baptista
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D001419:Bacteria / Q000187:drug effects; D017837:Bothrops / Q000378:metabolism*; D006461:Hemolysis; D006801:Humans; D007113:Immunity, Innate; D036341:Intercellular Signaling Peptides and Proteins; D008555:Melitten / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D013045:Species Specificity; D014688:Venoms / Q000737:chemistry*; D014862:Wasp Venoms / Q000737:chemistry; D054804:Cathelicidins
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014688:Venoms; D014862:Wasp Venoms; D008555:Melitten; C037500:mastoparan; D054804:Cathelicidins