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Antimalarial Exposure Delays Plasmodium falciparum Intra-Erythrocytic Cycle and Drives Drug Transporter Genes Expression

2010-08Journal article Open access
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dc.contributor.authorIsabel Veiga, Maria
dc.contributor.authorFerreira, Pedro
dc.contributor.authorSchmidt, Berit Aydin
dc.contributor.authorRibacke, Ulf
dc.contributor.authorBjorkman, Anders
dc.contributor.authorTichopad, Ales
dc.contributor.authorGil, José Pedro
dc.date.accessioned2018-12-07T14:52:45Z
dc.date.available2018-12-07T14:52:45Z
dc.date.issued2010-08
dc.description.abstractBackground: Multi-drug resistant Plasmodium falciparum is a major obstacle to malaria control and is emerging as a complex phenomenon. Mechanisms of drug evasion based on the intracellular extrusion of the drug and/or modification of target proteins have been described. However, cellular mechanisms related with metabolic activity have also been seen in eukaryotic systems, e. g. cancer cells. Recent observations suggest that such mechanism may occur in P. falciparum. Methodology/Principal Findings: We therefore investigated the effect of mefloquine exposure on the cell cycle of three P. falciparum clones (3D7, FCB, W2) with different drug susceptibilities, while investigating in parallel the expression of four genes coding for confirmed and putative drug transporters (pfcrt, pfmdr1, pfmrp1 and pfmrp2). Mefloquine induced a previously not described dose and clone dependent delay in the intra-erythrocytic cycle of the parasite. Drug impact on cell cycle progression and gene expression was then merged using a non-linear regression model to determine specific drug driven expression. This revealed a mild, but significant, mefloquine driven gene induction up to 1.5 fold. Conclusions/Significance: Both cell cycle delay and induced gene expression represent potentially important mechanisms for parasites to escape the effect of the antimalarial drug.
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]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1371/journal.pone.0012408
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10400.1/11192
dc.language.isoeng
dc.peerreviewedyes
dc.publisherPublic Library of Science
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectChloroquine resistance
dc.subjectMalaria parasites
dc.subjectCopy number
dc.subjectPfmdr1 Gene
dc.subjectIn-Vitro
dc.subjectArtemisinin
dc.subjectSensitivity
dc.subjectMefloquine
dc.subjectPfcrt
dc.subjectRecrudescence
dc.titleAntimalarial Exposure Delays Plasmodium falciparum Intra-Erythrocytic Cycle and Drives Drug Transporter Genes Expression
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue8
oaire.citation.startPagee12408
oaire.citation.titlePLoS ONE
oaire.citation.volume5
person.familyNameVeiga
person.familyNameFerreira
person.familyNameGil
person.givenNameMaria Isabel
person.givenNamePedro
person.givenNameJosé Pedro
person.identifier332675
person.identifier.ciencia-id271C-6028-9C6B
person.identifier.ciencia-id5E15-DD6D-50E6
person.identifier.ciencia-idD01A-B30E-BCD5
person.identifier.orcid0000-0002-2205-8102
person.identifier.orcid0000-0002-2682-7722
person.identifier.orcid0000-0002-6107-9379
person.identifier.ridH-9922-2018
person.identifier.ridQ-6748-2016
person.identifier.scopus-author-id12767840900
person.identifier.scopus-author-id55427200100
person.identifier.scopus-author-id7201625436
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublication76e56d6c-a7cb-4b41-8ad7-0e480b31ed41
relation.isAuthorOfPublicatione0a51049-1676-475b-a9e8-1d911386238d
relation.isAuthorOfPublicationcb728715-0e4c-4ae5-9e21-b6a8f35a8313
relation.isAuthorOfPublication.latestForDiscoverye0a51049-1676-475b-a9e8-1d911386238d

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