Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil

Detalhes bibliográficos
Autor(a) principal: Magalhães, Lucas Sousa
Data de Publicação: 2018
Outros Autores: Bomfim, Lays Gisele Santos, Mota, Sthefanne Gondim, Cruz, Geydson Silveira da, Corrêa, Cristiane Bani, Tanajura, Diego Moura, Lipscomb, Michael W, Borges, Valéria de Matos, Jesus, Amélia Maria Ribeiro de, Almeida, Roque Pacheco de, Moura, Tatiana Rodrigues de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/30670
Resumo: 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).
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spelling Magalhães, Lucas SousaBomfim, Lays Gisele SantosMota, Sthefanne GondimCruz, Geydson Silveira daCorrêa, Cristiane BaniTanajura, Diego MouraLipscomb, Michael WBorges, Valéria de MatosJesus, Amélia Maria Ribeiro deAlmeida, Roque Pacheco deMoura, Tatiana Rodrigues de2018-12-18T16:23:39Z2018-12-18T16:23:39Z2018MAGALHÃES, 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. 2018.0074-0276https://www.arca.fiocruz.br/handle/icict/3067010.1590/0074-02760170289CNPq, 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).Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil.Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil.Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil.Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil.Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil.Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil.Howard University. Department of Biology. Washington DC, United States of America.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil.Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil.Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil.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.engInstituto Oswaldo CruzLeishmaniaLeishmaniose visceralAntimônioResistência a drogasLeishmaniaVisceral leishmaniasisAntimonyDrug ResistanceIncreased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazilinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/30670/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALMagalhães LS Increased thiol levels in antimony.... 2018.pdfMagalhães LS Increased thiol levels in antimony.... 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dc.title.pt_BR.fl_str_mv Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil
title Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil
spellingShingle Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil
Magalhães, Lucas Sousa
Leishmania
Leishmaniose visceral
Antimônio
Resistência a drogas
Leishmania
Visceral leishmaniasis
Antimony
Drug Resistance
title_short Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil
title_full Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil
title_fullStr Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil
title_full_unstemmed Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil
title_sort Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil
author Magalhães, Lucas Sousa
author_facet Magalhães, Lucas Sousa
Bomfim, Lays Gisele Santos
Mota, Sthefanne Gondim
Cruz, Geydson Silveira da
Corrêa, Cristiane Bani
Tanajura, Diego Moura
Lipscomb, Michael W
Borges, Valéria de Matos
Jesus, Amélia Maria Ribeiro de
Almeida, Roque Pacheco de
Moura, Tatiana Rodrigues de
author_role author
author2 Bomfim, Lays Gisele Santos
Mota, Sthefanne Gondim
Cruz, Geydson Silveira da
Corrêa, Cristiane Bani
Tanajura, Diego Moura
Lipscomb, Michael W
Borges, Valéria de Matos
Jesus, Amélia Maria Ribeiro de
Almeida, Roque Pacheco de
Moura, Tatiana Rodrigues de
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Magalhães, Lucas Sousa
Bomfim, Lays Gisele Santos
Mota, Sthefanne Gondim
Cruz, Geydson Silveira da
Corrêa, Cristiane Bani
Tanajura, Diego Moura
Lipscomb, Michael W
Borges, Valéria de Matos
Jesus, Amélia Maria Ribeiro de
Almeida, Roque Pacheco de
Moura, Tatiana Rodrigues de
dc.subject.other.pt_BR.fl_str_mv Leishmania
Leishmaniose visceral
Antimônio
Resistência a drogas
topic Leishmania
Leishmaniose visceral
Antimônio
Resistência a drogas
Leishmania
Visceral leishmaniasis
Antimony
Drug Resistance
dc.subject.en.pt_BR.fl_str_mv Leishmania
Visceral leishmaniasis
Antimony
Drug Resistance
description 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).
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-12-18T16:23:39Z
dc.date.available.fl_str_mv 2018-12-18T16:23:39Z
dc.date.issued.fl_str_mv 2018
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv 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.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/30670
dc.identifier.issn.pt_BR.fl_str_mv 0074-0276
dc.identifier.doi.none.fl_str_mv 10.1590/0074-02760170289
identifier_str_mv 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.
0074-0276
10.1590/0074-02760170289
url https://www.arca.fiocruz.br/handle/icict/30670
dc.language.iso.fl_str_mv eng
language eng
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dc.publisher.none.fl_str_mv Instituto Oswaldo Cruz
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