pfmdr1 amplification is related to increased Plasmodium falciparum in vitro sensitivity to the bisquinoline piperaquine

Detalhes bibliográficos
Autor(a) principal: Veiga, M. I.
Data de Publicação: 2012
Outros Autores: Ferreira, P. E., Malmberg, M., Jörnhagen, L., Björkman, A., Nosten, F., Gil, J. P.
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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spelling 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
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection 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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