Vol 10: Metabolic QTL Analysis Links Chloroquine Resistance in Plasmodium falciparum to Impaired Hemoglobin Catabolism.Reportar como inadecuado



 Vol 10: Metabolic QTL Analysis Links Chloroquine Resistance in Plasmodium falciparum to Impaired Hemoglobin Catabolism.


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This article is from PLoS Genetics, volume 10.AbstractDrug 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.



Autor: Lewis, Ian A.; Wacker, Mark; Olszewski, Kellen L.; Cobbold, Simon A.; Baska, Katelynn S.; Tan, Asako; Ferdig, Michael T.; Llinas, Manuel

Fuente: https://archive.org/







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