Polymorphism in PfMRP1 (Plasmodium falciparum multidrug resistance protein 1) Amino Acid 1466 associated with resistance to Sulfadoxine-Pyrimethamine treatment
Autor(a) principal: | |
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Data de Publicação: | 2009 |
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/10400.1/11572 |
Resumo: | Sulfadoxine-pyrimethamine (SP) remains widely recommended for intermittent preventive treatment against Plasmodium falciparum malaria for pregnant women and infants in Africa. Resistance to SP is increasing and associated primarily with mutations in the P. falciparum dhfr (Pfdhfr) and Pfdhps genes. This study aimed to explore the hypothetical association of genetic alterations in the P. falciparum multidrug resistance protein gene (Pfmrp1) with the in vivo response to SP by detecting the selection of single nucleotide polymorphisms (SNPs) following standard single-dose treatment administered to children with acute uncomplicated P. falciparum malaria in Tanzania. We detected significant selection of parasites carrying the Pfmrp1 1466K allele in samples from children with recrudescent infections, with 12 (100%) of 12 such samples being positive for this allele, compared to 52 (67.5%) of 77 baseline samples (P=0.017), in parallel with the selection of the Pfdhfr Pfdhps quintuple mutant haplotype in cases of recrudescence (P=0.001). There was no association between the 1466K SNP and the Pfdhfr Pfdhps quintuple mutation, indicating independent selections. Our data point for the first time to a role for a P. falciparum multidrug resistance protein homologue in the antimalarial activity of SP. Moreover, they add to the growing evidence of the potential importance of Pfmrp1 in antimalarial drug resistance. |
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Polymorphism in PfMRP1 (Plasmodium falciparum multidrug resistance protein 1) Amino Acid 1466 associated with resistance to Sulfadoxine-Pyrimethamine treatmentAntifolate resistanceDihydropteroate-SynthetaseDihydrofolate-reductaseMalariaFolateMrp1ChemotherapyExpressionMutationsTransportSulfadoxine-pyrimethamine (SP) remains widely recommended for intermittent preventive treatment against Plasmodium falciparum malaria for pregnant women and infants in Africa. Resistance to SP is increasing and associated primarily with mutations in the P. falciparum dhfr (Pfdhfr) and Pfdhps genes. This study aimed to explore the hypothetical association of genetic alterations in the P. falciparum multidrug resistance protein gene (Pfmrp1) with the in vivo response to SP by detecting the selection of single nucleotide polymorphisms (SNPs) following standard single-dose treatment administered to children with acute uncomplicated P. falciparum malaria in Tanzania. We detected significant selection of parasites carrying the Pfmrp1 1466K allele in samples from children with recrudescent infections, with 12 (100%) of 12 such samples being positive for this allele, compared to 52 (67.5%) of 77 baseline samples (P=0.017), in parallel with the selection of the Pfdhfr Pfdhps quintuple mutant haplotype in cases of recrudescence (P=0.001). There was no association between the 1466K SNP and the Pfdhfr Pfdhps quintuple mutation, indicating independent selections. Our data point for the first time to a role for a P. falciparum multidrug resistance protein homologue in the antimalarial activity of SP. Moreover, they add to the growing evidence of the potential importance of Pfmrp1 in antimalarial drug resistance.SIDA/SAREC; Fundacao para a Ciencia e Tecnologia (FCT)/Ministerio da Ciencia e Ensino Superior, Portugal [SFRH/BD/28393/2006]; [SWE-2007-174]; [SWE-2005-027]American Society for MicrobiologySapientiaDahlstrom, SabinaVeiga, M. IsabelMartensson, AndreasBjorkman, AndersGil, J. P.2018-12-07T14:53:34Z2009-062009-06-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/11572eng0066-480410.1128/AAC.00091-09info: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:RCAAP2023-07-24T10:23:24Zoai:sapientia.ualg.pt:10400.1/11572Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:03:03.661825Repositório 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 |
Polymorphism in PfMRP1 (Plasmodium falciparum multidrug resistance protein 1) Amino Acid 1466 associated with resistance to Sulfadoxine-Pyrimethamine treatment |
title |
Polymorphism in PfMRP1 (Plasmodium falciparum multidrug resistance protein 1) Amino Acid 1466 associated with resistance to Sulfadoxine-Pyrimethamine treatment |
spellingShingle |
Polymorphism in PfMRP1 (Plasmodium falciparum multidrug resistance protein 1) Amino Acid 1466 associated with resistance to Sulfadoxine-Pyrimethamine treatment Dahlstrom, Sabina Antifolate resistance Dihydropteroate-Synthetase Dihydrofolate-reductase Malaria Folate Mrp1 Chemotherapy Expression Mutations Transport |
title_short |
Polymorphism in PfMRP1 (Plasmodium falciparum multidrug resistance protein 1) Amino Acid 1466 associated with resistance to Sulfadoxine-Pyrimethamine treatment |
title_full |
Polymorphism in PfMRP1 (Plasmodium falciparum multidrug resistance protein 1) Amino Acid 1466 associated with resistance to Sulfadoxine-Pyrimethamine treatment |
title_fullStr |
Polymorphism in PfMRP1 (Plasmodium falciparum multidrug resistance protein 1) Amino Acid 1466 associated with resistance to Sulfadoxine-Pyrimethamine treatment |
title_full_unstemmed |
Polymorphism in PfMRP1 (Plasmodium falciparum multidrug resistance protein 1) Amino Acid 1466 associated with resistance to Sulfadoxine-Pyrimethamine treatment |
title_sort |
Polymorphism in PfMRP1 (Plasmodium falciparum multidrug resistance protein 1) Amino Acid 1466 associated with resistance to Sulfadoxine-Pyrimethamine treatment |
author |
Dahlstrom, Sabina |
author_facet |
Dahlstrom, Sabina Veiga, M. Isabel Martensson, Andreas Bjorkman, Anders Gil, J. P. |
author_role |
author |
author2 |
Veiga, M. Isabel Martensson, Andreas Bjorkman, Anders Gil, J. P. |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Sapientia |
dc.contributor.author.fl_str_mv |
Dahlstrom, Sabina Veiga, M. Isabel Martensson, Andreas Bjorkman, Anders Gil, J. P. |
dc.subject.por.fl_str_mv |
Antifolate resistance Dihydropteroate-Synthetase Dihydrofolate-reductase Malaria Folate Mrp1 Chemotherapy Expression Mutations Transport |
topic |
Antifolate resistance Dihydropteroate-Synthetase Dihydrofolate-reductase Malaria Folate Mrp1 Chemotherapy Expression Mutations Transport |
description |
Sulfadoxine-pyrimethamine (SP) remains widely recommended for intermittent preventive treatment against Plasmodium falciparum malaria for pregnant women and infants in Africa. Resistance to SP is increasing and associated primarily with mutations in the P. falciparum dhfr (Pfdhfr) and Pfdhps genes. This study aimed to explore the hypothetical association of genetic alterations in the P. falciparum multidrug resistance protein gene (Pfmrp1) with the in vivo response to SP by detecting the selection of single nucleotide polymorphisms (SNPs) following standard single-dose treatment administered to children with acute uncomplicated P. falciparum malaria in Tanzania. We detected significant selection of parasites carrying the Pfmrp1 1466K allele in samples from children with recrudescent infections, with 12 (100%) of 12 such samples being positive for this allele, compared to 52 (67.5%) of 77 baseline samples (P=0.017), in parallel with the selection of the Pfdhfr Pfdhps quintuple mutant haplotype in cases of recrudescence (P=0.001). There was no association between the 1466K SNP and the Pfdhfr Pfdhps quintuple mutation, indicating independent selections. Our data point for the first time to a role for a P. falciparum multidrug resistance protein homologue in the antimalarial activity of SP. Moreover, they add to the growing evidence of the potential importance of Pfmrp1 in antimalarial drug resistance. |
publishDate |
2009 |
dc.date.none.fl_str_mv |
2009-06 2009-06-01T00:00:00Z 2018-12-07T14:53:34Z |
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/10400.1/11572 |
url |
http://hdl.handle.net/10400.1/11572 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0066-4804 10.1128/AAC.00091-09 |
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 |
publisher.none.fl_str_mv |
American Society for Microbiology |
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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1799133265201725440 |