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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/11319
Title: Novel polymorphisms in plasmodium falciparum ABC transporter genes are associated with major ACT Antimalarial drug resistance
Authors: Maria Isabel Veiga
Pedro Eduardo Ferreira
Louise Jörnhagen
Maja Malmberg
Aminatou Kone
Berit Aydin Schmidt
Max Petzold
Anders Björkman
Francois Nosten
Jose Pedro Gil
Karolinska Institutet
Universidade do Algarve
Nordiska Hogskolan for folkhalsovetenskap
Shoklo Malaria Research Unit
Mahidol University
Nuffield Department of Clinical Medicine
Binghamton University State University of New York
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology
Issue Date: 30-May-2011
Citation: PLoS ONE. Vol.6, No.5 (2011)
Abstract: Chemotherapy 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. © 2011 Veiga, et al.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=79957470784&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/11319
ISSN: 19326203
Appears in Collections:Scopus 2011-2015

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