pfmdr1 amplification is related to increased Plasmodium falciparum in vitro sensitivity to the bisquinoline piperaquine
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/24147 |
Resumo: | The Shoklo Malaria Research Unit is part of the Mahidol Oxford University Tropical Medicine Research Unit, supported by the Wellcome Trust of Great Britain. |
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pfmdr1 amplification is related to increased Plasmodium falciparum in vitro sensitivity to the bisquinoline piperaquinePlasmodium falciparumPiperaquinepfmdr1CNVScience & TechnologyThe Shoklo Malaria Research Unit is part of the Mahidol Oxford University Tropical Medicine Research Unit, supported by the Wellcome Trust of Great Britain.The 4-aminoquinoline bisquinoline piperaquine is an important partner drug in one of the presently recommended artemisinin combination therapies. Recent clinical trials have confirmed its high efficacy in combination with dihydroartemisinin. Resistance to piperaquine alone has, however, been documented. Amplification in copy number of the Plasmodium falciparum multidrug resistance locus on chromosome 5, containing the pfmdr1 gene, has been shown to confer resistance to structurally unrelated antimalarials. Through the determination of the 50% inhibitory concentrations (IC(50)s) and IC(90)s for piperaquine and chloroquine in a set of 46 adapted P. falciparum cultures originating from the Thai-Burmese border, we have characterized the regions around the pfmdr1 gene and identified a significant association between the presence of pfmdr1 duplications and enhanced sensitivity to piperaquine (P = 0.005 for IC(50) and P = 0.002 for IC(90)) and chloroquine, reaching statistical significance at IC(90)s (P = 0.026). These results substantiate the potential importance of pfmdr1 copy number amplifications in the efficacy of the combination therapy piperaquine-dihydroartemisinin. It supports the rational use of 4-aminoquinolines and artemisinin-based compounds, as they independently select for mutually incompatible combinations of mutations.This work was supported by project grants from Swedish Development Cooperation Agency-Department for Research Cooperation (SWE 2005-0017, SWE 2005-4596, SWE-2007-174, and SWE-2005-4027). M.I.V. was supported by a postdoctoral grant from Fundação para a Ciência e Tecnologia (FCT)/Ministerio da Ciência e Ensino Superior, Portugal MCES (SFRH/BPD/76614/2011).American Society for Microbiology (ASM)Universidade do MinhoVeiga, M. I.Ferreira, P. E.Malmberg, M.Jörnhagen, L.Björkman, A.Nosten, F.Gil, J. P.2012-072012-07-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/24147eng0066-480410.1128/AAC.06350-1122508315http://dx.doi.org/10.1128%2FAAC.06350-11info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:11:43Zoai:repositorium.sdum.uminho.pt:1822/24147Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:03:32.102812Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
pfmdr1 amplification is related to increased Plasmodium falciparum in vitro sensitivity to the bisquinoline piperaquine |
title |
pfmdr1 amplification is related to increased Plasmodium falciparum in vitro sensitivity to the bisquinoline piperaquine |
spellingShingle |
pfmdr1 amplification is related to increased Plasmodium falciparum in vitro sensitivity to the bisquinoline piperaquine Veiga, M. I. Plasmodium falciparum Piperaquine pfmdr1 CNV Science & Technology |
title_short |
pfmdr1 amplification is related to increased Plasmodium falciparum in vitro sensitivity to the bisquinoline piperaquine |
title_full |
pfmdr1 amplification is related to increased Plasmodium falciparum in vitro sensitivity to the bisquinoline piperaquine |
title_fullStr |
pfmdr1 amplification is related to increased Plasmodium falciparum in vitro sensitivity to the bisquinoline piperaquine |
title_full_unstemmed |
pfmdr1 amplification is related to increased Plasmodium falciparum in vitro sensitivity to the bisquinoline piperaquine |
title_sort |
pfmdr1 amplification is related to increased Plasmodium falciparum in vitro sensitivity to the bisquinoline piperaquine |
author |
Veiga, M. I. |
author_facet |
Veiga, M. I. Ferreira, P. E. Malmberg, M. Jörnhagen, L. Björkman, A. Nosten, F. Gil, J. P. |
author_role |
author |
author2 |
Ferreira, P. E. Malmberg, M. Jörnhagen, L. Björkman, A. Nosten, F. Gil, J. P. |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Veiga, M. I. Ferreira, P. E. Malmberg, M. Jörnhagen, L. Björkman, A. Nosten, F. Gil, J. P. |
dc.subject.por.fl_str_mv |
Plasmodium falciparum Piperaquine pfmdr1 CNV Science & Technology |
topic |
Plasmodium falciparum Piperaquine pfmdr1 CNV Science & Technology |
description |
The Shoklo Malaria Research Unit is part of the Mahidol Oxford University Tropical Medicine Research Unit, supported by the Wellcome Trust of Great Britain. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-07 2012-07-01T00:00:00Z |
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.uri.fl_str_mv |
http://hdl.handle.net/1822/24147 |
url |
http://hdl.handle.net/1822/24147 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0066-4804 10.1128/AAC.06350-11 22508315 http://dx.doi.org/10.1128%2FAAC.06350-11 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
American Society for Microbiology (ASM) |
publisher.none.fl_str_mv |
American Society for Microbiology (ASM) |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799132441892356096 |