Identification of the drug/metabolite transporter 1 as a marker of quinine resistance in a NF54×Cam3.II <i>P. falciparum</i> genetic cross.

ABSTRACT: The genetic basis of Plasmodium falciparum resistance to quinine (QN), a drug used to treat severe malaria, has long been enigmatic. To gain further insight, we used FRG-NOD human liver-chimeric mice to conduct a P. falciparum genetic cross between QN-sensitive and QN-resistant parasites, which also differ in their susceptibility to chloroquine (CQ). By applying different selective conditions to progeny pools prior to cloning, we recovered 120 unique recombinant progeny. These progeny were subjected to drug profiling and QTL analyses with QN, CQ, and monodesethyl-CQ (md-CQ, the active metabolite of CQ), which revealed predominant peaks on chromosomes 7 and 12, consistent with a multifactorial mechanism of resistance. A shared chromosome 12 region mapped to resistance to all t

SUBMITTER: Kanai M 

PROVIDER: S-EPMC11463348 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature