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Plasmodium falciparum multidrug resistance protein 1 and artemisinin-based combination therapy in Africa

2009-11Journal article Open access
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dc.contributor.authorDahlstrom, Sabina
dc.contributor.authorFerreira, Pedro
dc.contributor.authorVeiga, Maria Isabel
dc.contributor.authorSedighi, Nazli
dc.contributor.authorWiklund, Lisa
dc.contributor.authorMartensson, Andreas
dc.contributor.authorFarnert, Anna
dc.contributor.authorSisowath, Christin
dc.contributor.authorOsorio, Lyda
dc.contributor.authorDarban, Hamid
dc.contributor.authorAndersson, Bjoern
dc.contributor.authorKaneko, Akira
dc.contributor.authorConseil, Gwanaelle
dc.contributor.authorBjorkman, Anders
dc.contributor.authorGil, José Pedro
dc.date.accessioned2018-12-07T14:58:00Z
dc.date.available2018-12-07T14:58:00Z
dc.date.issued2009-11
dc.description.abstractPlasmodium falciparum response mechanisms to the major artemisinin-based combination therapies (ACTs) are largely unknown. Multidrug-resistance protein (MRP)-like adenosine triphosphate (ATP)-binding cassette transporters are known to be related to multidrug resistance in many organisms. Therefore, we hypothesized that sequence variation in pfmrp1 can contribute to decreased parasite sensitivity to ACT. Through sequencing of the pfmrp1 open reading frame for 103 geographically diverse P. falciparum infections, we identified 27 single-nucleotide polymorphisms (SNPs), of which 21 were nonsynonymous and 6 synonymous. Analyses of clinical efficacy trials with artesunate-amodiaquine and artemether-lumefantrine detected a specific selection of the globally prevalent I876V SNP in recurrent infections after artemether-lumefantrine treatment. Additional in silico studies suggested an influence of variation in amino acid 876 on the ATP hydrolysis cycle of pfMRP1 with potential impact on protein functionality. Our data suggest for the first time, to our knowledge, the involvement of pfMRP1 in P. falciparum in vivo response to ACT.
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1086/606009
dc.identifier.issn0022-1899
dc.identifier.urihttp://hdl.handle.net/10400.1/11805
dc.language.isoeng
dc.peerreviewedyes
dc.publisherUniversity of Chicago Press
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAntimalarial-drug resistance
dc.subjectIn-vivo selection
dc.subjectArtemether-lumefantrine
dc.subjectTopology prediction
dc.subjectMalaria
dc.subjectPfmdr1
dc.subjectPfcrt
dc.subjectAmodiaquine
dc.subjectChloroquine
dc.subjectGenes
dc.titlePlasmodium falciparum multidrug resistance protein 1 and artemisinin-based combination therapy in Africa
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1464
oaire.citation.issue9
oaire.citation.startPage1456
oaire.citation.titleJournal of Infectious Diseases
oaire.citation.volume200
person.familyNameFerreira
person.familyNameVeiga
person.familyNameGil
person.givenNamePedro
person.givenNameMaria Isabel
person.givenNameJosé Pedro
person.identifier332675
person.identifier.ciencia-id5E15-DD6D-50E6
person.identifier.ciencia-id271C-6028-9C6B
person.identifier.ciencia-idD01A-B30E-BCD5
person.identifier.orcid0000-0002-2682-7722
person.identifier.orcid0000-0002-2205-8102
person.identifier.orcid0000-0002-6107-9379
person.identifier.ridQ-6748-2016
person.identifier.ridH-9922-2018
person.identifier.scopus-author-id55427200100
person.identifier.scopus-author-id12767840900
person.identifier.scopus-author-id7201625436
rcaap.rightsopenAccess
rcaap.typearticle
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relation.isAuthorOfPublication76e56d6c-a7cb-4b41-8ad7-0e480b31ed41
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relation.isAuthorOfPublication.latestForDiscoverycb728715-0e4c-4ae5-9e21-b6a8f35a8313

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