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Polymorphism in PfMRP1 (Plasmodium falciparum multidrug resistance protein 1) Amino Acid 1466 associated with resistance to Sulfadoxine-Pyrimethamine treatment

2009-06Journal article Open access
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dc.contributor.authorDahlstrom, Sabina
dc.contributor.authorVeiga, M. Isabel
dc.contributor.authorMartensson, Andreas
dc.contributor.authorBjorkman, Anders
dc.contributor.authorGil, J. P.
dc.date.accessioned2018-12-07T14:53:34Z
dc.date.available2018-12-07T14:53:34Z
dc.date.issued2009-06
dc.description.abstractSulfadoxine-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.
dc.description.sponsorshipSIDA/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]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1128/AAC.00091-09
dc.identifier.issn0066-4804
dc.identifier.urihttp://hdl.handle.net/10400.1/11572
dc.language.isoeng
dc.peerreviewedyes
dc.publisherAmerican Society for Microbiology
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAntifolate resistance
dc.subjectDihydropteroate-Synthetase
dc.subjectDihydrofolate-reductase
dc.subjectMalaria
dc.subjectFolate
dc.subjectMrp1
dc.subjectChemotherapy
dc.subjectExpression
dc.subjectMutations
dc.subjectTransport
dc.titlePolymorphism in PfMRP1 (Plasmodium falciparum multidrug resistance protein 1) Amino Acid 1466 associated with resistance to Sulfadoxine-Pyrimethamine treatment
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F28393%2F2006/PT
oaire.citation.endPage2556
oaire.citation.issue6
oaire.citation.startPage2553
oaire.citation.titleAntimicrobial Agents and Chemotherapy
oaire.citation.volume53
oaire.fundingStreamSFRH
person.familyNameVeiga
person.familyNameGil
person.givenNameMaria Isabel
person.givenNameJosé Pedro
person.identifier.ciencia-id271C-6028-9C6B
person.identifier.ciencia-idD01A-B30E-BCD5
person.identifier.orcid0000-0002-2205-8102
person.identifier.orcid0000-0002-6107-9379
person.identifier.ridH-9922-2018
person.identifier.scopus-author-id12767840900
person.identifier.scopus-author-id7201625436
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublication76e56d6c-a7cb-4b41-8ad7-0e480b31ed41
relation.isAuthorOfPublicationcb728715-0e4c-4ae5-9e21-b6a8f35a8313
relation.isAuthorOfPublication.latestForDiscovery76e56d6c-a7cb-4b41-8ad7-0e480b31ed41
relation.isProjectOfPublication56071233-45b4-43c0-94af-d234eaa0e892
relation.isProjectOfPublication.latestForDiscovery56071233-45b4-43c0-94af-d234eaa0e892

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