Metabolic QTL Analysis Links Chloroquine Resistance in Plasmodium falciparum to Impaired Hemoglobin Catabolism
نویسندگان
چکیده
Drug resistant strains of the malaria parasite, Plasmodium falciparum, have rendered chloroquine ineffective throughout much of the world. In parts of Africa and Asia, the coordinated shift from chloroquine to other drugs has resulted in the near disappearance of chloroquine-resistant (CQR) parasites from the population. Currently, there is no molecular explanation for this phenomenon. Herein, we employ metabolic quantitative trait locus mapping (mQTL) to analyze progeny from a genetic cross between chloroquine-susceptible (CQS) and CQR parasites. We identify a family of hemoglobin-derived peptides that are elevated in CQR parasites and show that peptide accumulation, drug resistance, and reduced parasite fitness are all linked in vitro to CQR alleles of the P. falciparum chloroquine resistance transporter (pfcrt). These findings suggest that CQR parasites are less fit because mutations in pfcrt interfere with hemoglobin digestion by the parasite. Moreover, our findings may provide a molecular explanation for the reemergence of CQS parasites in wild populations.
منابع مشابه
Clinical Pharmacology of the Antimalarial Chloroquine in Children and Their Mothers
Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium knowlesi are the parasites that infect humans. Plasmodium falciparum and Plasmodium vivax cause most of the malarial infections worldwide. Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium knowlesi are susceptible to chloroquine. Chloroquine was the world's most widely used antim...
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One of the main problems in malaria control is the resistance of Plasmodium falciparum to chloroquine and some other antimalarial drugs. This resistance is now quite common in most regions where falciparum malaria is endemic. Between 1968 and 1976, two in-vivo studies were carried out in endemic areas in the south of Iran and they showed P. falciparum to be chloroquine-sensitive. In 1983, the D...
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عنوان ژورنال:
دوره 10 شماره
صفحات -
تاریخ انتشار 2014