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

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.     

Application of Perturbation Simulations in Population Risk Assessment for Different Life History Strategies and Elasticity Patterns

Population structure and life history strategies are determinants of how populations respond to stressor-induced impairments in organism-level responses. Effects on population growth rate were modeled using seven theoretical constructs that represented the life history strategies and elasticity patterns of a broad range of species. Simulations of low to high ranges of simultaneous reductions in survival and reproduction were conducted and results indicated that stressor impacts on population growth rate were a function of population characteristics and the magnitude of the stress. Species that had high reproductive elasticity had greater population-level impacts than species with high survival elasticity for the same organism-level effects. Perturbation simulations were performed to assess the extinction risk in two species with similar elasticity patterns but different life history strategies: mysid shrimp, Americamysis bahia, and the gypsy moth, Lymantria dispar, which can be related to classical K- and r-strategists, respectively. Deterministic extinction risk was greater for the K-strategist, which indicated that population level risks were dependent on life history strategies, and toxicity values (e.g., LC50s) should be interpreted with caution. Ecological risk assessments should consider both population structure and life history strategy of an ecological receptor, in addition to the intrinsic sensitivity of the species to contaminant stressors.