Journal article

Metabolic QTL Analysis Links Chloroquine Resistance in Plasmodium falciparum to Impaired Hemoglobin Catabolism

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

PLoS Genetics | PUBLIC LIBRARY SCIENCE | Published : 2014

Abstract

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 re..

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University of Melbourne Researchers

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Awarded by NIH


Awarded by EuPathDB


Awarded by Center for Quantitative Biology


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Awarded by OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH


Funding Acknowledgements

This work was funded in part by the Burroughs Welcome Fund (Investigators in Pathogenesis of Infectious Disease Award for Research, ML), an NIH Director's New Innovators award (1DP2OD001315-01, ML), the NIH (RO1 A1071121, T32 GM075762, MTF), a subcontract from EuPathDB (HHSN272200900038C, ML and MTF) and support from the Center for Quantitative Biology (P50 GM071508). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.