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Novel polymorphisms in plasmodium falciparum ABC transporter genes are associated with major ACT antimalarial drug resistance

2011-05Journal article Open access
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dc.contributor.authorVeiga, Maria Isabel
dc.contributor.authorPousão-Ferreira, Pedro
dc.contributor.authorJornhagen, Louise
dc.contributor.authorMalmberg, Maja
dc.contributor.authorKone, Aminatou
dc.contributor.authorSchmidt, Berit Aydin
dc.contributor.authorPetzold, Max
dc.contributor.authorBjorkman, Anders
dc.contributor.authorNosten, Francois
dc.contributor.authorGil, José Pedro
dc.date.accessioned2018-12-07T14:57:52Z
dc.date.available2018-12-07T14:57:52Z
dc.date.issued2011-05
dc.description.abstractChemotherapy is a critical component of malaria control. However, the most deadly malaria pathogen, Plasmodium falciparum, has repeatedly mounted resistance against a series of antimalarial drugs used in the last decades. Southeast Asia is an epicenter of emerging antimalarial drug resistance, including recent resistance to the artemisinins, the core component of all recommended antimalarial combination therapies. Alterations in the parasitic membrane proteins Pgh-1, PfCRT and PfMRP1 are believed to be major contributors to resistance through decreasing intracellular drug accumulation. The pfcrt, pfmdr1 and pfmrp1 genes were sequenced from a set of P. falciparum field isolates from the Thai-Myanmar border. In vitro drug susceptibility to artemisinin, dihydroartemisinin, mefloquine and lumefantrine were assessed. Positive correlations were seen between the in vitro susceptibility responses to artemisinin and dihydroartemisinin and the responses to the arylamino-alcohol quinolines lumefantrine and mefloquine. The previously unstudied pfmdr1 F1226Y and pfmrp1 F1390I SNPs were associated significantly with artemisinin, mefloquine and lumefantrine in vitro susceptibility. A variation in pfmdr1 gene copy number was also associated with parasite drug susceptibility of artemisinin, mefloquine and lumefantrine. Our work unveils new candidate markers of P. falciparum multidrug resistance in vitro, while contributing to the understanding of subjacent genetic complexity, essential for future evidence-based drug policy decisions.
dc.description.sponsorshipSwedish Development Cooperation Agency-Department for Research Cooperation [SWE 2005-0017, SWE 2005-4596, SWE-2007-174, SWE-2005-4027]; Fundacao para a Ciencia e Tecnologia (FCT)/Ministerio da Ciencia e Ensino Superior, Portugal-MCES [SFRH/BD/28393/2006, SFRH/BD/28368/2006]; Wellcome Trust of Great Britain
dc.identifier.doi10.1371/journal.pone.0020212
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10400.1/11741
dc.language.isoeng
dc.peerreviewedyes
dc.publisherPublic Library Science
dc.relationCALCIUM OSCILLATIONS IN HUMAN MALARIA PARASITE: IMPLICATIONS FOR THE MECHANISM OF ACTION OF ARTEMISININ AGAINST PLASMODIUM FALCIPARUM
dc.subjectPfmdr1 Copy Number
dc.subjectIn-Vivo Selection
dc.subjectArtemether-Lumefantrine
dc.subjectSubstrate-Specificity
dc.subjectArtemisinin Resistance
dc.subjectChloroquine Resistance
dc.subjectMefloquine Resistance
dc.subjectCombination Therapy
dc.subjectMalaria Parasite
dc.subjectAmino-Acids
dc.titleNovel polymorphisms in plasmodium falciparum ABC transporter genes are associated with major ACT antimalarial drug resistance
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCALCIUM OSCILLATIONS IN HUMAN MALARIA PARASITE: IMPLICATIONS FOR THE MECHANISM OF ACTION OF ARTEMISININ AGAINST PLASMODIUM FALCIPARUM
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F28393%2F2006/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F28368%2F2006/PT
oaire.citation.issue5
oaire.citation.startPagee20212
oaire.citation.titlePlos One
oaire.citation.volume6
oaire.fundingStreamSFRH
person.familyNameVeiga
person.familyNamePousão-Ferreira
person.familyNameGil
person.givenNameMaria Isabel
person.givenNamePedro
person.givenNameJosé Pedro
person.identifier.ciencia-id271C-6028-9C6B
person.identifier.ciencia-id5A11-AB29-0849
person.identifier.ciencia-idD01A-B30E-BCD5
person.identifier.orcid0000-0002-2205-8102
person.identifier.orcid0000-0001-6746-764X
person.identifier.orcid0000-0002-6107-9379
person.identifier.ridH-9922-2018
person.identifier.ridH-3689-2014
person.identifier.scopus-author-id12767840900
person.identifier.scopus-author-id6506349877
person.identifier.scopus-author-id7201625436
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
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