Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/100186
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dc.contributor.authorVeiga, Maria Isabelen
dc.contributor.authorOsório, Nuno S.en
dc.contributor.authorFerreira, Pedro Eduardoen
dc.contributor.authorFranzén, Oscaren
dc.contributor.authorDahlstrom, Sabinaen
dc.contributor.authorLum, J. Kojien
dc.contributor.authorNosten, Francoisen
dc.contributor.authorGil, José Pedroen
dc.date.accessioned2015-05-26T08:43:39Zen
dc.date.accessioned2019-12-06T20:18:03Z-
dc.date.available2015-05-26T08:43:39Zen
dc.date.available2019-12-06T20:18:03Z-
dc.date.copyright2014en
dc.date.issued2014en
dc.identifier.citationVeiga, M. I., Osório, N. S., Ferreira, P. E., Franzén, O., Dahlstrom, S., Lum, J. K., et al. (2014). Complex polymorphisms in the plasmodium falciparum multidrug resistance protein 2 gene and its contribution to antimalarial response. Antimicrobial agents and chemotherapy, 58(12), 7390-7397.en
dc.identifier.urihttps://hdl.handle.net/10356/100186-
dc.description.abstractPlasmodium falciparum has the capacity to escape the actions of essentially all antimalarial drugs. ATP-binding cassette (ABC) transporter proteins are known to cause multidrug resistance in a large range of organisms, including the Apicomplexa parasites. P. falciparum genome analysis has revealed two genes coding for the multidrug resistance protein (MRP) type of ABC transporters: Pfmrp1, previously associated with decreased parasite drug susceptibility, and the poorly studied Pfmrp2. The role of Pfmrp2 polymorphisms in modulating sensitivity to antimalarial drugs has not been established. We herein report a comprehensive account of the Pfmrp2 genetic variability in 46 isolates from Thailand. A notably high frequency of 2.8 single nucleotide polymorphisms (SNPs)/kb was identified for this gene, including some novel SNPs. Additionally, we found that Pfmrp2 harbors a significant number of microindels, some previously not reported. We also investigated the potential association of the identified Pfmrp2 polymorphisms with altered in vitro susceptibility to several antimalarials used in artemisinin-based combination therapy and with parasite clearance time. Association analysis suggested Pfmrp2 polymorphisms modulate the parasite's in vitro response to quinoline antimalarials, including chloroquine, piperaquine, and mefloquine, and association with in vivo parasite clearance. In conclusion, our study reveals that the Pfmrp2 gene is the most diverse ABC transporter known in P. falciparum with a potential role in antimalarial drug resistance.en
dc.format.extent8 p.en
dc.language.isoenen
dc.relation.ispartofseriesAntimicrobial agents and chemotherapyen
dc.rights© 2014 American Society for Microbiology. This paper was published in Antimicrobial Agents and Chemotherapy and is made available as an electronic reprint (preprint) with permission of American Society for Microbiology. The paper can be found at the following official DOI: [http://dx.doi.org/10.1128/AAC.03337-14]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.en
dc.subjectDRNTU::Science::Biological sciences::Microbiologyen
dc.titleComplex polymorphisms in the plasmodium falciparum multidrug resistance protein 2 gene and its contribution to antimalarial responseen
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen
dc.identifier.doi10.1128/AAC.03337-14en
dc.description.versionPublished versionen
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