Antimicrobial peptides isolated from Phyllomedusa nordestina (Amphibia) alter the permeability of plasma membrane of Leishmania and Trypanosoma cruzi

Autor(es)

Pinto, Erika Gracielle ^{[1, 2]} ; Pimenta, Daniel C. ^[3] ; Antoniazzi, Marta Maria ^[4] ; Jared, Carlos ^[4] ; Tempone, Andre Gustavo ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Med Trop Sao Paulo, BR-05403000 Sao Paulo - Brazil

^[2] Adolfo Lutz Inst, Dept Parasitol, BR-01246000 Sao Paulo - Brazil

^[3] Inst Butantan, Lab Bioquim & Biofis, BR-05503900 Sao Paulo - Brazil

^[4] Inst Butantan, Lab Biol Ceular, BR-05503900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental Parasitology; v. 135, n. 4, p. 655-660, DEC 2013.
• Citações Web of Science: 22

Resumo

Nature has provided inspiration for Drug Discovery studies and amphibian secretions have been used as a promising source of effective peptides which could be explored as novel drug prototypes for neglected parasitic diseases as Leishmaniasis and Chagas disease. In this study, we isolated four antimicrobial peptides (AMPS) from Phyllomedusa nordestina secretion, and studied their effectiveness against Leishmania (L) infantum and Trypanosoma cruzi. The antiparasitic fractions were characterized by mass spectrometry and Edman degradation, leading to the identification of dermaseptins 1 and 4 and phylloseptins 7 and 8. T. cruzi trypomastigotes were susceptible to peptides, showing IC50 values in the range concentration of 0.25-0.68 mu M. Leishmania (L.) infantum showed susceptibility to phylloseptin 7, presenting an IC50 value of 10 mu M. Except for phylloseptin 7 which moderate showed cytotoxicity (IC50 (=) 34 mu M), the peptides induced no cellular damage to mammalian cells. The lack of rnitochondrial oxidative activity of parasites detected by the MTT assay, suggested that peptides were leishmanicidal and trypanocidal. By using the fluorescent probe SYTOX (R) Green, dermaseptins 1 and 4 and phylloseptins 7 and 8 showed time-dependent plasma membrane permeabilization of T. cruzi; phylloseptin 7 also showed a similar effect in Leishmania parasites. The present study demonstrates for the first time that AMPs target the plasma membrane of Leishmania and T. cruzi, leading to cellular death. Considering the potential of amphibian peptides against protozoan parasites and the reduced mammalian toxicity, they may contribute as scaffolds for drug design studies. (C) 2013 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 09/12236-3 - Isolamento, caracterização e atividade anti-leishmania e anti-trypanosoma cruzi de compostos bioativos de venenos de anfíbios brasileiros
• Beneficiário: Érika Gracielle Pinto
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 08/09260-7 - Combinações terapêuticas na leishmaniose visceral: o potencial anti-leishmania de bloqueadores de canais de cálcio e o uso de nanoformulações lipossomais
• Beneficiário: André Gustavo Tempone Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Regular