Author | Magalhães, Lucas Sousa | |
Author | Bomfim, Lays Gisele Santos | |
Author | Mota, Sthefanne Gondim | |
Author | Cruz, Geydson Silveira da | |
Author | Corrêa, Cristiane Bani | |
Author | Tanajura, Diego Moura | |
Author | Lipscomb, Michael W | |
Author | Borges, Valéria de Matos | |
Author | Jesus, Amélia Maria Ribeiro de | |
Author | Almeida, Roque Pacheco de | |
Author | Moura, Tatiana Rodrigues de | |
Access date | 2018-12-18T16:23:39Z | |
Available date | 2018-12-18T16:23:39Z | |
Document date | 2018 | |
Citation | MAGALHÃES, L. S. et al. Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil. Memórias do Instituto Oswaldo Cruz, Rio de Janeiro, v. 113, n. 2, p. 119-125, feb. 2018. | pt_BR |
ISSN | 0074-0276 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/30670 | |
Sponsorship | CNPq, MCTI/CNPQ/Universal 14/2014 (460743/2014-
7 TRM) and PROCAD/CASADINHO (552721/2011-5 RPA); FAPITEC/
SE/FUNTEC/CNPq No. 12/2009 (019.203.02712/2009-8 ARJ); CAPES;
Programa Nacional de Incentivo à Pesquisa em Parasitologia Básica, Edital
No. 032/2010 (ARJ); NIH (grant #SC2GM103741 - MWL); the Department
of Defense (DOD) (grant #W911NF-14-1-0123 - MWL); and the National
Science Foundation (NSF) (grant #1428768 - MWL). | pt_BR |
Language | eng | pt_BR |
Publisher | Instituto Oswaldo Cruz | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Leishmania | pt_BR |
Subject in Portuguese | Leishmaniose visceral | pt_BR |
Subject in Portuguese | Antimônio | pt_BR |
Subject in Portuguese | Resistência a drogas | pt_BR |
Title | Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil | pt_BR |
Type | Article | pt_BR |
DOI | 10.1590/0074-02760170289 | |
Abstract | BACKGROUND Treatment-refractory visceral leishmaniasis (VL) has become an important problem in many countries. OBJECTIVES We evaluated the antimony-resistance mechanisms of Leishmania infantum isolated from VL patients refractory or responsive to treatment with pentavalent antimony. METHODS Strains isolated from antimony-refractory patients (in vitro antimony-resistant isolates) and antimony-responsive patients (in vitro antimony-sensitive isolates) were examined. Morphological changes were evaluated by transmission electron microscopy after trivalent antimony exposure. P-glycoprotein (P-gp) efflux pump activity was evaluated using the pump-specific inhibitor verapamil hydrochloride, and the role of thiol in trivalent antimony resistance was investigated using the enzymatic inhibitor L-buthionine sulfoximine. FINDINGS Antimony treatment induced fewer alterations in the cellular structure of L. infantum resistant isolates than in that of sensitive isolates. P-gp efflux activity was not involved in antimony resistance in these isolates. Importantly, the resistant isolates contained higher levels of thiol compared to the sensitive isolates, and inhibition of thiol synthesis in the resistant isolates recovered their sensitivity to trivalent antimony treatment, and enhanced the production of reactive oxygen species in promastigotes exposed to the drug. MAIN CONCLUSIONS Our results demonstrate that isolates from patients with antimony-refractory VL exhibited higher thiol levels than antimony-sensitive isolates. This indicates that redox metabolism plays an important role in the antimony-resistance of New World VL isolates. | pt_BR |
Affilliation | Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil. | pt_BR |
Affilliation | Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil. | pt_BR |
Affilliation | Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil. | pt_BR |
Affilliation | Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil. | pt_BR |
Affilliation | Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil. | pt_BR |
Affilliation | Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil. | pt_BR |
Affilliation | Howard University. Department of Biology. Washington DC, United States of America. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Affilliation | Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil. | pt_BR |
Affilliation | Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil. | pt_BR |
Affilliation | Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil. | pt_BR |
Subject | Leishmania | pt_BR |
Subject | Visceral leishmaniasis | pt_BR |
Subject | Antimony | pt_BR |
Subject | Drug Resistance | pt_BR |