The dinoponeratoxin peptides from the giant ant Dinoponera quadriceps display in vitro antitrypanosomal activity
-
Dânya Bandeira Lima
and Alice Maria Costa Martins
Abstract
The crude venom of the giant ant Dinoponera quadriceps is a cocktail of polypeptides and organic compounds that shows antiparasitic effects against Trypanosoma cruzi, the causative agent of Chagas disease. In order to investigate the venom-derived components responsible for such antitrypanosomal activity, four dinoponeratoxins (DnTxs) were identified, namely M-PONTX-Dq3a, -Dq3b, -Dq3c and -Dq4e, that are diverse in size, net charge, hydrophobicity and propensity to interact with eukaryote cell membranes. These peptides were tested against epimastigote, trypomastigote and amastigote forms of benznidazole (Bz)-resistant Y strain of T. cruzi and in mammalian host cells. The M-PONTX-Dq3a and -Dq4e inhibited all developmental forms of T. cruzi, including amastigotes, the responsible form for the maintenance of infection on chronic phase of the disease. The M-PONTX-Dq3a showed the highest selectivity index (SI) (80) and caused morphological alterations in T. cruzi, as observed by scanning electron microscopy (SEM), and induced cell death through necrosis, as seen by multiparametric flow cytometry analysis with specific biochemical markers. Altogether, the D. quadriceps venom appears as a source for the prospection of trypanocidal peptides and the M-PONTX-Dq3a arises as a candidate among the dinoponeratoxin-related peptides in the development of compounds against Chagas disease.
Acknowledgments
The authors are grateful for the funding agencies, the Brazilian National Council for Scientific and Technological Development (CNPq), the Ministry of Science, Technology and Innovation (MCTI) and the Coordination for the Improvement of Higher Education Personnel (CAPES), the Ministry of Education and Culture, both of the Federal Government of Brazil, for the financial support of the project development and the fellowships of graduate students, respectively. We are also thankful to the Analytical Center Core Facility of the Federal University of Ceará for the technical support on Electron Microscopy studies. Our deepest thanks to Professor Katsuhiro Konno, Institute of Natural Medicine, University of Toyama, Toyama, Japan, and Dr. André J. Zaharenko and Dr. Álvaro Rossan B. Prieto-da-Silva, Laboratory of Genetics, Institute Butantan, São Paulo, Brazil, for the preliminary proteomic and peptidome analysis of D. quadriceps crude venom.
Conflict of interest statement: Authors declare no conflict of interest.
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Supplemental Material:
The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2017-0198).
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