Involvement of nucleoside diphosphate kinase b and elongation factor 2 in Leishmania braziliensis antimony resistance phenotype

Detalhes bibliográficos
Autor(a) principal: Moreira, Douglas de Souza
Data de Publicação: 2016
Outros Autores: Murta, Silvane Maria Fonseca
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/23651
Resumo: Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
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spelling Moreira, Douglas de SouzaMurta, Silvane Maria Fonseca2017-12-13T17:44:03Z2017-12-13T17:44:03Z2016MOREIRA, Douglas de Souza; MURTA, Silvane Maria Fonseca. Involvement of nucleoside diphosphate kinase b and elongation factor 2 in Leishmania braziliensis antimony resistance phenotype.Parasit Vectors, v. 9., p.641, 2016.1756-3305https://www.arca.fiocruz.br/handle/icict/2365110.1186/s13071-016-1930-6engBioMed CentralLeishmania spp.,Leishmania spp.,Nucleoside diphosphate kinase bElongation factor 2ChemotherapyAntimony resistanceInvolvement of nucleoside diphosphate kinase b and elongation factor 2 in Leishmania braziliensis antimony resistance phenotypeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, BrazilBackground: Nucleoside diphosphate kinase b (NDKb) is responsible for nucleoside triphosphates synthesis and it has key role in the purine metabolism in trypanosomatid protozoans. Elongation factor 2 (EF2) is an important factor for protein synthesis. Recently, our phosphoproteomic analysis demonstrated that NDKb and EF2 proteins were phosphorylated and dephosphorylated in antimony (SbIII)-resistant L. braziliensis line compared to its SbIII-susceptible pair, respectively. Methods; In this study, the overexpression of NDKb and EF2 genes in L. braziliensis and L. infantum was performed to investigate the contribution of these proteins in the SbIII-resistance phenotype. Furthermore, we examined the role of lamivudine on SbIII susceptibility in clones that overexpress the NDKb gene, and the effect of EF2 kinase (EF2K) inhibitor on the growth of EF2-overexpressing parasites. Results: Western blot analysis demonstrated that NDKb and EF2 proteins are more and less expressed, respectively, in SbIII-resistant line of L. braziliensis than its wild-type (WTS) counterpart, corroborating our previous phosphoproteomic data. NDKb or EF2-overexpressing L. braziliensis lines were 1.6 to 2.1-fold more resistant to SbIII than the untransfected WTS line. In contrast, no difference in SbIII susceptibility was observed in L. infantum parasites overexpressing NDKb or EF2. Susceptibility assays showed that NDKb-overexpressing L. braziliensis lines presented elevated resistance to lamivudine, an antiviral agent, but it did not alter the leishmanicidal activity in association with SbIII. EF2-overexpressing L. braziliensis clone was slightly more resistant to EF2K inhibitor than the WTS line. Surprisingly, this inhibitor increased the antileishmanial effect of SbIII, suggesting that this association might be a valuable strategy for leishmaniasis chemotherapy. Conclusion: Our findings represent the first study of NDKb and EF2 genes overexpression that demonstrates an increase of SbIII resistance in L. braziliensis which can contribute to develop new strategies for leishmaniasis treatment.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83082https://www.arca.fiocruz.br/bitstream/icict/23651/1/license.txt9193a7c197bc67acd023525e72a03240MD51ORIGINALInvolvement of nucleoside diphosphate .pdfInvolvement of nucleoside diphosphate .pdfapplication/pdf13262803https://www.arca.fiocruz.br/bitstream/icict/23651/2/Involvement%20of%20nucleoside%20diphosphate%20.pdf09bae760f7624e67eb06a2fb6d51fa8bMD52TEXTInvolvement of nucleoside diphosphate .pdf.txtInvolvement of nucleoside diphosphate .pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Involvement of nucleoside diphosphate kinase b and elongation factor 2 in Leishmania braziliensis antimony resistance phenotype
title Involvement of nucleoside diphosphate kinase b and elongation factor 2 in Leishmania braziliensis antimony resistance phenotype
spellingShingle Involvement of nucleoside diphosphate kinase b and elongation factor 2 in Leishmania braziliensis antimony resistance phenotype
Moreira, Douglas de Souza
Leishmania spp.,
Leishmania spp.,
Nucleoside diphosphate kinase b
Elongation factor 2
Chemotherapy
Antimony resistance
title_short Involvement of nucleoside diphosphate kinase b and elongation factor 2 in Leishmania braziliensis antimony resistance phenotype
title_full Involvement of nucleoside diphosphate kinase b and elongation factor 2 in Leishmania braziliensis antimony resistance phenotype
title_fullStr Involvement of nucleoside diphosphate kinase b and elongation factor 2 in Leishmania braziliensis antimony resistance phenotype
title_full_unstemmed Involvement of nucleoside diphosphate kinase b and elongation factor 2 in Leishmania braziliensis antimony resistance phenotype
title_sort Involvement of nucleoside diphosphate kinase b and elongation factor 2 in Leishmania braziliensis antimony resistance phenotype
author Moreira, Douglas de Souza
author_facet Moreira, Douglas de Souza
Murta, Silvane Maria Fonseca
author_role author
author2 Murta, Silvane Maria Fonseca
author2_role author
dc.contributor.author.fl_str_mv Moreira, Douglas de Souza
Murta, Silvane Maria Fonseca
dc.subject.other.pt_BR.fl_str_mv Leishmania spp.,
topic Leishmania spp.,
Leishmania spp.,
Nucleoside diphosphate kinase b
Elongation factor 2
Chemotherapy
Antimony resistance
dc.subject.en.pt_BR.fl_str_mv Leishmania spp.,
Nucleoside diphosphate kinase b
Elongation factor 2
Chemotherapy
Antimony resistance
description Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
publishDate 2016
dc.date.issued.fl_str_mv 2016
dc.date.accessioned.fl_str_mv 2017-12-13T17:44:03Z
dc.date.available.fl_str_mv 2017-12-13T17:44:03Z
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 MOREIRA, Douglas de Souza; MURTA, Silvane Maria Fonseca. Involvement of nucleoside diphosphate kinase b and elongation factor 2 in Leishmania braziliensis antimony resistance phenotype.Parasit Vectors, v. 9., p.641, 2016.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/23651
dc.identifier.issn.pt_BR.fl_str_mv 1756-3305
dc.identifier.doi.none.fl_str_mv 10.1186/s13071-016-1930-6
identifier_str_mv MOREIRA, Douglas de Souza; MURTA, Silvane Maria Fonseca. Involvement of nucleoside diphosphate kinase b and elongation factor 2 in Leishmania braziliensis antimony resistance phenotype.Parasit Vectors, v. 9., p.641, 2016.
1756-3305
10.1186/s13071-016-1930-6
url https://www.arca.fiocruz.br/handle/icict/23651
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/23651/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/23651/2/Involvement%20of%20nucleoside%20diphosphate%20.pdf
https://www.arca.fiocruz.br/bitstream/icict/23651/3/Involvement%20of%20nucleoside%20diphosphate%20.pdf.txt
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