ArticlePLoS genetics2014
Metabolic QTL analysis links chloroquine resistance in Plasmodium falciparum to impaired hemoglobin catabolism.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 93 citations in OpenAlex.
- Rhomboid Proteases in Plasmodium spp. : Biology, Functional Roles, and Therapeutic Potential.Acta parasitologica · 2026Review
- Identification of genetic markers of quinine partial resistance in Plasmodium falciparum.Nature microbiology · 2026Article
- A Multidimensional Analysis of the Bimodal Piperaquine Response inbioRxiv : the preprint server for biology · 2026Article
- Gain-of-function PfAAT1 mutations compensate for impaired PfCRT function inResearch square · 2026Article
- Molecular basis of the functional conflict between chloroquine and peptide transport in the Malaria parasite chloroquine resistance transporter PfCRT.Nature communications · 2025Article
- Assessing fitness costs in malaria parasites: a comprehensive review and implications for drug resistance management.Malaria journal · 2025Review
- Exploiting integrative metabolomics to study host-parasite interactions in Plasmodium infections.Trends in parasitology · 2024Review
- Structures ofBiochemistry · 2023Article
- Mutant PfCRT Can Mediate Piperaquine Resistance in African Plasmodium falciparum With Reduced Fitness and Increased Susceptibility to Other Antimalarials.The Journal of infectious diseases · 2022Article
- Piperaquine-resistant PfCRT mutations differentially impact drug transport, hemoglobin catabolism and parasite physiology in Plasmodium falciparum asexual blood stages.PLoS pathogens · 2022Article
- The Knock-Down of the Chloroquine Resistance Transporter PfCRT Is Linked to Oligopeptide Handling in Plasmodium falciparum.Microbiology spectrum · 2022Article
- Evidence for the early emergence of piperaquine-resistant Plasmodium falciparum malaria and modeling strategies to mitigate resistance.PLoS pathogens · 2022Article
- Biomarker enrichment medium: A defined medium for metabolomic analysis of microbial pathogens.Frontiers in microbiology · 2022Article
- Method for absolute quantification of short chain fatty acids via reverse phase chromatography mass spectrometry.PloS one · 2022Article
- An Uninvited Seat at the Dinner Table: How Apicomplexan Parasites Scavenge Nutrients from the Host.Microorganisms · 2021Review
- Insights from Leishmania (Viannia) guyanensis in vitro behavior and intercellular communication.Parasites & vectors · 2021Article
- Genomic and Genetic Approaches to Studying Antimalarial Drug Resistance and Plasmodium Biology.Trends in parasitology · 2021Review
- Article
- Methods Used to Investigate theFrontiers in cellular and infection microbiology · 2021Review
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
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 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.
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