title: Anthelmintic effects of a cationic toxin from a South American rattlesnake venom.
abstract: Despite the unquestionable importance of the highly cationic feature of several small polypeptides with high content of positively charged amino acids for their biological activities, positively charged peptides do not necessarily have the capacity to cross the cell membranes. Interestingly, we found that crotamine, a positively charged amphiphilic peptide from the South American rattlesnake venom, has a unique cell-penetrating property with affinity for acidic vesicles, besides a well-characterized antimicrobial and antitumoral activities. In spite of a remarkable in vitro antifungal activity of crotamine against Candida spp., no significant effect of this peptide could be observed in the course of Candida albicans and Candida krusei infection on Caenorhabditis elegans asssed in vivo. These experiments, in which the nematode C. elegans was used as a living host, suggested, however, the potential anthelmintic activity of crotamine because of its uptake by the worms and accumulation in their acidic compartments. As described in the present work, this lysosomotropic property is consistent with a previously proposed mechanism of toxicity of crotamine on mammalian tumoral cell lines. This study also allowed us to propose the cationic peptides with lysosomotropic property, as crotamine, as a potential new class of anthelmentics with ability to overcome the challenging problems of drug resistance.
authors.affiliation: Departamento de Farmacologia, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Dal Mas
authors.affiliation: Departamento de Farmacologia, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil.
authors.forename: J T
authors.initials: JT
authors.lastname: Moreira
authors.affiliation: Departamento de Biofísica, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil.
authors.forename: S
authors.initials: S
authors.lastname: Pinto
authors.affiliation: Departamento de Farmacologia, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil.
authors.forename: G G
authors.initials: GG
authors.lastname: Monte
authors.affiliation: Departamento de Farmacologia, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil.
authors.forename: M B
authors.initials: MB
authors.lastname: Nering
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade de São Paulo (USP-RP), Ribeirão Preto, Brazil.
authors.forename: E B
authors.initials: EB
authors.lastname: Oliveira
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo (UNIFESP), Santos, SP, Brazil.
authors.forename: M L
authors.initials: ML
authors.lastname: Gazarini
authors.affiliation: Departamento de Biofísica, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Mori
authors.affiliation: Departamento de Farmacologia, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil. Electronic address: mhayashi.unifesp@gmail.com.
authors.forename: M A F
authors.initials: MA
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D002176:Candida albicans / Q000502:physiology; D003435:Crotalid Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity
chemical_list: D000871:Anthelmintics; D003435:Crotalid Venoms; C010563:crotamine
keywords: Acidic compartments; Anthelmintic; Caenorhabditis elegans; Crotamine; Lysossomotropic; Snake toxin; Worms