Interaction of the Rattlesnake Toxin Crotamine with Model Membranes

Interaction of the Rattlesnake Toxin Crotamine with Model Membranes

Author Costa, Bruno A. Autor UNIFESP Google Scholar
Sanches, Leonardo Google Scholar
Gomide, Andreza Barbosa Google Scholar
Bizerra, Fernando Autor UNIFESP Google Scholar
Dal Mas, Caroline Autor UNIFESP Google Scholar
Oliveira, Eduardo B. Google Scholar
Perez, Katia Regina Autor UNIFESP Google Scholar
Itri, Rosangela Google Scholar
Oguiura, Nancy Google Scholar
Hayashi, Mirian A. F. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Inst Butantan
Universidade de São Paulo (USP)
Abstract Crotamine is one of the main constituents of the venom of the South American rattlesnake Crotalus durissus terrificus. A common gene ancestry and structural similarity with the antimicrobial beta-defensins (identical disulfide bond pattern and highly positive net charge) suggested potential antimicrobial activities for this snake toxin. Although crotamine demonstrated low activity against both Gram-positive and Gram-negative bacteria, a pronounced antifungal activity was observed against Candida spp., Trichosporon spp., and Cryptococcus neoformans. Crotamine's selective antimicrobial properties, with no observable hemolytic activity, stimulated us to evaluate the potential applications of this polypeptide as an antiyeast or candicidal agent for medical and industrial application. Aiming to understand the mechanism(s) of action underlying crotamine antimicrobial activity and its selectivity for fungi, we present herein studies using membrane model systems (i.e., large unilamellar vesicles, LUVs, and giant unilamellar vesicles, GUVs), with different phospholipid compositions. We show here that crotamine presents a higher lytic activity on negatively charged membranes compared with neutral membranes, with or without cholesterol or ergosterol content. the vesicle burst was not preceded by membrane permeabilization as is generally observed for pore forming peptides. Although such a property of disrupting lipid membranes is very important to combat multiresistant fungi, no inhibitory activity was observed for crotamine against biofilms formed by several Candida spp. strains, except for a limited effect against C. krusei biofilm.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Biotox Network (CYTED)
Date 2014-05-22
Published in Journal of Physical Chemistry B. Washington: Amer Chemical Soc, v. 118, n. 20, p. 5471-5479, 2014.
ISSN 1520-6106 (Sherpa/Romeo, impact factor)
Publisher Amer Chemical Soc
Extent 5471-5479
Access rights Closed access
Type Article
Web of Science ID WOS:000336510300019

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