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Globally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibility to artemisinin-based combination therapies

Veiga, M. Isabel; Dhingra, Satish K.; Henrich, Philipp P.; Straimer, Judith; Gnadig, Nina; Uhlemann, Anne-Catrin; Martin, Rowena; Lehane, Adele; Fidock, David A


Antimalarial chemotherapy, globally reliant on artemisinin-based combination therapies (ACTs), is threatened by the spread of drug resistance in Plasmodium falciparum parasites. Here we use zinc-finger nucleases to genetically modify the multidrug resistance-1 transporter PfMDR1 at amino acids 86 and 184, and demonstrate that the widely prevalent N86Y mutation augments resistance to the ACT partner drug amodiaquine and the former first-line agent chloroquine. In contrast, N86Y increases...[Show more]

CollectionsANU Research Publications
Date published: 2016
Type: Journal article
Source: Nature Communications
DOI: 10.1038/ncomms11553
Access Rights: Open Access


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