Unraveling the antifungal activity of a South American rattlesnake toxin crotamine
| Autor: | Pedro Ismael da Silva, Gabriel L. C. Nunes, Ana O. de Souza, Tetsuo Yamane, Eduardo B. Oliveira, Jéssica T. Moreira, Richard L. Karpel, Ismael Dale Cotrim Guerreiro da Silva, Mirian A. F. Hayashi, Mohsen Rajabi, Fernando César Bizerra, Erica S. Yamane |
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| Rok vydání: | 2013 |
| Předmět: |
Antifungal Agents
beta-Defensins Cell Survival Molecular Sequence Data Microbial Sensitivity Tests Trichophyton rubrum Antimicrobial activity Gram-Positive Bacteria medicine.disease_cause Biochemistry Cell Line Aspergillus fumigatus Microbiology Minimum inhibitory concentration Crotalid Venoms Gram-Negative Bacteria Escherichia coli medicine Animals Humans Amino Acid Sequence TESTES DE SENSIBILIDADE MICROBIANA Candida albicans Cryptococcus neoformans Microbial Viability Dose-Response Relationship Drug biology Toxin Crotalus Fungi Clinical strain General Medicine biology.organism_classification Recombinant Proteins Anti-Bacterial Agents Crotamine Rattlesnake toxin Amphipathic peptide Micrococcus luteus |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | Crotamine is a highly basic peptide from the venom of Crotalus durissus terrificus rattlesnake. Its common gene ancestry and structural similarity with the β-defensins, mainly due to an identical disulfide bond pattern, stimulated us to assess the antimicrobial properties of native, recombinant, and chemically synthesized crotamine. Antimicrobial activities against standard strains and clinical isolates were analyzed by the colorimetric microdilution method showing a weak antibacterial activity against both Gram-positive and Gram-negative bacteria [MIC (Minimum Inhibitory Concentration) of 50–>200 μg/mL], with the exception of Micrococcus luteus [MIC ranging from 1 to 2 μg/mL]. No detectable activity was observed for the filamentous fungus Aspergillus fumigatus and Trichophyton rubrum at concentrations up to 125 μg/mL. However, a pronounced antifungal activity against Candida spp., Trichosporon spp., and Cryptococcus neoformans [12.5–50.0 μg/mL] was observed. Chemically produced synthetic crotamine in general displayed MIC values similar to those observed for native crotamine, whereas recombinant crotamine was overridingly more potent in most assays. On the other hand, derived short linear peptides were not very effective apart from a few exceptions. Pronounced ultrastructure alteration in Candida albicans elicited by crotamine was observed by electron microscopy analyses. The peculiar specificity for highly proliferating cells was confirmed here showing potential low cytotoxic effect of crotamine against nontumoral mammal cell lines (HEK293, PC12, and primary culture astrocyte cells) compared to tumoral B16F10 cells, and no hemolytic activity was observed. Taken together these results suggest that, at low concentration, crotamine is a potentially valuable anti-yeast or candicidal agent, with low harmful effects on normal mammal cells, justifying further studies on its mechanisms of action aiming medical and industrial applications. |
| Databáze: | OpenAIRE |
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