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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/34160
Title: Complex polymorphisms in the Plasmodium falciparum multidrug resistance protein 2 gene and its contribution to antimalarial response
Authors: Maria Isabel Veiga
Nuno S. Osório
Pedro Eduardo Ferreira
Oscar Franzén
Sabina Dahlstrom
J. Koji Lum
Francois Nosten
José Pedro Gil
Universidade do Minho, Escola de Ciencias da Saude
ICVS/3B's
Karolinska Institutet
Nanyang Technological University
Universidade de Lisboa
Binghamton University State University of New York
Shoklo Malaria Research Unit
Mahidol University
Nuffield Department of Clinical Medicine
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Dec-2014
Citation: Antimicrobial Agents and Chemotherapy. Vol.58, No.12 (2014), 7390-7397
Abstract: Copyright © 2014, American Society for Microbiology. All Rights Reserved. Plasmodium 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.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84912552005&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/34160
ISSN: 10986596
00664804
Appears in Collections:Scopus 2011-2015

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