Proteomic analysis of the soluble proteomes of miltefosine-sensitive and -resistant Leishmania infantum chagasi isolates obtained from Brazilian patients with different treatment outcomes
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/10978 |
Resumo: | Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Laboratório de Leishmanioses. Departamento de Ciências Fisiológicas. Laboratório de Química de Proteínas. Vitória, ES, Brasil. |
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Carnielli, Juliana B. TAndrade, Hélida M. dePìres, Simone FChapeaurouge, Alexander DPerales, JonasRocha, Renata MontiCarvalho, Silvio F. G.Ribeiro, Leonardo PDietze, ReynaldoFigueiredo, Suely GLemos, Elenice M2015-06-26T13:04:36Z2015-06-26T13:04:36Z2014CARNIELLI, Juliana B. T. et al. Proteomic analysis of the soluble proteomes of miltefosine-sensitive and -resistant Leishmania infantum chagasi isolates obtained from Brazilian patients with different treatment outcomes. Journal of Proteomics, v.108, p.198-208, aug. 2014.1874-3919https://www.arca.fiocruz.br/handle/icict/1097810.1016/j.jprot.2014.05.010engElsevierProteomic analysis of the soluble proteomes of miltefosine-sensitive and -resistant Leishmania infantum chagasi isolates obtained from Brazilian patients with different treatment outcomesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Laboratório de Leishmanioses. Departamento de Ciências Fisiológicas. Laboratório de Química de Proteínas. Vitória, ES, Brasil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Laboratório de Leishmanioses. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Laboratório de Leishmanioses. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Laboratório de Leishmanioses. Vitória, ES. Brasil.Universidade Estadual de Montes Claros. Hospital Universitário Clemente de Faria. Montes Claros, MG, Brasil.Universidade Federal do Espírito Santo. Departamento de Ciências Fisiológicas. Laboratório de Química de Proteínas. Vitória, ES, Brasil.Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Laboratório de Leishmanioses. Vitória, ES. Brasil.Universidade Federal do Espírito Santo. Departamento de Ciências Fisiológicas. Laboratório de Química de Proteínas. Vitória, ES, Brasil.Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Laboratório de Leishmanioses. Vitória, ES. Brasil.The mechanism of miltefosine-resistance in Leishmania spp. has been partially determined in experimental resistant lines; however, studies using clinical isolates with different miltefosine susceptibilities are still needed. In our study, we used a proteomic 2D-DIGE/MS approach to study different protein abundances in miltefosine-sensitive and -resistant Leishmania infantum chagasi isolates from visceral leishmaniasis patients with different miltefosine treatment outcomes. The high-resolution proteome obtained from these isolates showed 823 matched spots and 46 spots exhibited different abundances between the isolates. Out of these differentially expressed spots, 26 (56.5%) showed greater and 20 (43.5%) showed lower expression of the resistant isolate compared to the sensitive isolate. MALDI/TOF–TOF mass spectrometry allowed the identification of 32 spots with unique protein identification correspondent to 22 non-redundant proteins. Most of the proteins up-regulated in the proteome miltefosine-resistant isolates were associated with redox homeostasis, stress response, protection to apoptosis, and drug translocation. These differentially expressed proteins are likely involved in miltefosine natural resistance and suggest that the miltefosine-resistance mechanism in Leishmania is multifactorial. Biological significance Visceral leishmaniasis (VL) is a serious disease with a challenging treatment plan requiring the prolonged and painful applications of poorly tolerated toxic drugs. Therefore, the identification of miltefosine, an effective and safe oral drug, was considered a significant advancement in leishmaniasis therapy. However, different sensitivities to miltefosine in Leishmania have been observed in clinically relevant species, and the biological mechanism by which clinical isolates of Leishmania acquire drug resistance is poorly understood. Our work aims to elucidate the mechanism of natural resistance to miltefosine in Leishmania by studying the isolates from VL patients who displayed different miltefosine treatment outcomes.Leishmania infantum chagasiBrazilTreatmentProteômicaLeishmania infantuminfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1914https://www.arca.fiocruz.br/bitstream/icict/10978/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALalexaner_chapeaurougeetal_IOC_2014.pdfapplication/pdf818523https://www.arca.fiocruz.br/bitstream/icict/10978/2/alexaner_chapeaurougeetal_IOC_2014.pdfe87c9b729c84a36d7b775e4cd4c8781eMD52TEXTalexaner_chapeaurougeetal_IOC_2014.pdf.txtalexaner_chapeaurougeetal_IOC_2014.pdf.txtExtracted texttext/plain52730https://www.arca.fiocruz.br/bitstream/icict/10978/3/alexaner_chapeaurougeetal_IOC_2014.pdf.txtc24ee41f30264673c8f6f07f01e47c7bMD53icict/109782023-09-05 10:22:59.553oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-05T13:22:59Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
dc.title.pt_BR.fl_str_mv |
Proteomic analysis of the soluble proteomes of miltefosine-sensitive and -resistant Leishmania infantum chagasi isolates obtained from Brazilian patients with different treatment outcomes |
title |
Proteomic analysis of the soluble proteomes of miltefosine-sensitive and -resistant Leishmania infantum chagasi isolates obtained from Brazilian patients with different treatment outcomes |
spellingShingle |
Proteomic analysis of the soluble proteomes of miltefosine-sensitive and -resistant Leishmania infantum chagasi isolates obtained from Brazilian patients with different treatment outcomes Carnielli, Juliana B. T Leishmania infantum chagasi Brazil Treatment Proteômica Leishmania infantum |
title_short |
Proteomic analysis of the soluble proteomes of miltefosine-sensitive and -resistant Leishmania infantum chagasi isolates obtained from Brazilian patients with different treatment outcomes |
title_full |
Proteomic analysis of the soluble proteomes of miltefosine-sensitive and -resistant Leishmania infantum chagasi isolates obtained from Brazilian patients with different treatment outcomes |
title_fullStr |
Proteomic analysis of the soluble proteomes of miltefosine-sensitive and -resistant Leishmania infantum chagasi isolates obtained from Brazilian patients with different treatment outcomes |
title_full_unstemmed |
Proteomic analysis of the soluble proteomes of miltefosine-sensitive and -resistant Leishmania infantum chagasi isolates obtained from Brazilian patients with different treatment outcomes |
title_sort |
Proteomic analysis of the soluble proteomes of miltefosine-sensitive and -resistant Leishmania infantum chagasi isolates obtained from Brazilian patients with different treatment outcomes |
author |
Carnielli, Juliana B. T |
author_facet |
Carnielli, Juliana B. T Andrade, Hélida M. de Pìres, Simone F Chapeaurouge, Alexander D Perales, Jonas Rocha, Renata Monti Carvalho, Silvio F. G. Ribeiro, Leonardo P Dietze, Reynaldo Figueiredo, Suely G Lemos, Elenice M |
author_role |
author |
author2 |
Andrade, Hélida M. de Pìres, Simone F Chapeaurouge, Alexander D Perales, Jonas Rocha, Renata Monti Carvalho, Silvio F. G. Ribeiro, Leonardo P Dietze, Reynaldo Figueiredo, Suely G Lemos, Elenice M |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Carnielli, Juliana B. T Andrade, Hélida M. de Pìres, Simone F Chapeaurouge, Alexander D Perales, Jonas Rocha, Renata Monti Carvalho, Silvio F. G. Ribeiro, Leonardo P Dietze, Reynaldo Figueiredo, Suely G Lemos, Elenice M |
dc.subject.en.pt_BR.fl_str_mv |
Leishmania infantum chagasi Brazil Treatment |
topic |
Leishmania infantum chagasi Brazil Treatment Proteômica Leishmania infantum |
dc.subject.decs.pt_BR.fl_str_mv |
Proteômica Leishmania infantum |
description |
Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Laboratório de Leishmanioses. Departamento de Ciências Fisiológicas. Laboratório de Química de Proteínas. Vitória, ES, Brasil. |
publishDate |
2014 |
dc.date.issued.fl_str_mv |
2014 |
dc.date.accessioned.fl_str_mv |
2015-06-26T13:04:36Z |
dc.date.available.fl_str_mv |
2015-06-26T13:04:36Z |
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 |
CARNIELLI, Juliana B. T. et al. Proteomic analysis of the soluble proteomes of miltefosine-sensitive and -resistant Leishmania infantum chagasi isolates obtained from Brazilian patients with different treatment outcomes. Journal of Proteomics, v.108, p.198-208, aug. 2014. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/10978 |
dc.identifier.issn.pt_BR.fl_str_mv |
1874-3919 |
dc.identifier.doi.pt_BR.fl_str_mv |
10.1016/j.jprot.2014.05.010 |
identifier_str_mv |
CARNIELLI, Juliana B. T. et al. Proteomic analysis of the soluble proteomes of miltefosine-sensitive and -resistant Leishmania infantum chagasi isolates obtained from Brazilian patients with different treatment outcomes. Journal of Proteomics, v.108, p.198-208, aug. 2014. 1874-3919 10.1016/j.jprot.2014.05.010 |
url |
https://www.arca.fiocruz.br/handle/icict/10978 |
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eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
dc.publisher.none.fl_str_mv |
Elsevier |
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Elsevier |
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reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
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FIOCRUZ |
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