Inhibition of malaria parasite Plasmodium falciparum development by crotamine, a cell penetrating peptide from the snake venom

Inhibition of malaria parasite Plasmodium falciparum development by crotamine, a cell penetrating peptide from the snake venom

Author Maluf, Sarah El Chamy Autor UNIFESP Google Scholar
Dal Mas, Caroline Autor UNIFESP Google Scholar
Oliveira, E. B. Google Scholar
Melo, P. M. Autor UNIFESP Google Scholar
Carmona, Adriana Karaoglanovic Autor UNIFESP Google Scholar
Gazarini, Marcos Leoni Autor UNIFESP Google Scholar
Hayashi, Mirian Akemi Furuie Autor UNIFESP Google Scholar
Abstract We show here that crotamine, a polypeptide from the South American rattlesnake venom with cell penetrating and selective anti-fungal and anti-tumoral properties, presents a potent anti-plasmodial activity in culture. Crotamine inhibits the development of the Plasmodium falciparum parasites in a dose-dependent manner [IC50 value of 1.87 mu M], and confocal microscopy analysis showed a selective internalization of fluorescent-labeled crotamine into P. falciparum infected erythrocytes, with no detectable fluorescence in uninfected healthy erythrocytes. In addition, similarly to the crotamine cytotoxic effects, the mechanism underlying the anti-plasmodial activity may involve the disruption of parasite acidic compartments H+ homeostasis. In fact, crotamine promoted a reduction of parasites organelle fluorescence loaded with the lysosomotropic fluorochrome acridine orange, in the same way as previously observed mammalian tumoral cells. Taken together, we show for the first time crotamine not only compromised the metabolism of the P. falciparum, but this toxin also inhibited the parasite growth. Therefore, we suggest this snake polypeptide as a promising lead molecule for the development of potential new molecules, namely peptidomimetics, with selectivity for infected erythrocytes and ability to inhibit the malaria infection by its natural affinity for acid vesicles. (C) 2016 Elsevier Inc. All rights reserved.
Keywords Plasmodium
Parasites
Crotamine
Antimalarial
Acidic compartments
Peptide trafficking
xmlui.dri2xhtml.METS-1.0.item-coverage New York
Language English
Sponsor Fundacao de Amparo Pesquisa do Estado de Sao Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
Date 2016
Published in Peptides. New York, v. 78, p. 11-16, 2016.
ISSN 0196-9781 (Sherpa/Romeo, impact factor)
Publisher Elsevier Science Inc
Extent 11-16
Origin http://dx.doi.org/10.1016/j.peptides.2016.01.013
Access rights Closed access
Type Article
Web of Science ID WOS:000372718700002
URI https://repositorio.unifesp.br/handle/11600/56177

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