ArticleMolecular microbiology2015
Balancing drug resistance and growth rates via compensatory mutations in the Plasmodium falciparum chloroquine resistance transporter.
Article in Molecular microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 54 citations in OpenAlex.
- Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration.Malaria journal · 2016Trial
- Intermittent Preventive Treatment with Dihydroartemisinin-Piperaquine in Ugandan Schoolchildren Selects for Plasmodium falciparum Transporter Polymorphisms That Modify Drug Sensitivity.Antimicrobial agents and chemotherapy · 2016Trial
- Identification of genetic markers of quinine partial resistance in Plasmodium falciparum.Nature microbiology · 2026Article
- Article
- Plasmodium falciparum African PfCRT Mutant Isoforms Conducive to Piperaquine Resistance Are Infrequent and Impart a Major Fitness Cost.The Journal of infectious diseases · 2025Article
- Temporal Patterns of Haplotypic and Allelic Diversity Reflect the Changing Selection Landscape of the Malaria Parasite Plasmodium falciparum.Molecular biology and evolution · 2025Article
- Assessing fitness costs in malaria parasites: a comprehensive review and implications for drug resistance management.Malaria journal · 2025Review
- Article
- Article
- 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
- Assessing risks of Plasmodium falciparum resistance to select next-generation antimalarials.Trends in parasitology · 2021Review
- Novel Antimalarial Tetrazoles and Amides Active against the Hemoglobin Degradation Pathway inJournal of medicinal chemistry · 2021Article
- The natural function of the malaria parasite's chloroquine resistance transporter.Nature communications · 2020Article
- Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda.Malaria journal · 2020Article
- Genetic mapping of fitness determinants across the malaria parasite Plasmodium falciparum life cycle.PLoS genetics · 2019Article
- The genomic architecture of antimalarial drug resistance.Briefings in functional genomics · 2019Review
- Pairwise growth competitions identify relative fitness relationships among artemisinin resistant Plasmodium falciparum field isolates.Malaria journal · 2019Article
- Phosphomimetic substitution at Ser-33 of the chloroquine resistance transporter PfCRT reconstitutes drug responses inThe Journal of biological chemistry · 2019Article
- Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
The widespread use of chloroquine to treat Plasmodium falciparum infections has resulted in the selection and dissemination of variant haplotypes of the primary resistance determinant PfCRT. These haplotypes have encountered drug pressure and within-host competition with wild-type drug-sensitive parasites. To examine these selective forces in vitro, we genetically engineered P. falciparum to express geographically diverse PfCRT haplotypes. Variant alleles from the Philippines (PH1 and PH2, which differ solely by the C72S mutation) both conferred a moderate gain of chloroquine resistance and a reduction in growth rates in vitro. Of the two, PH2 showed higher IC50 values, contrasting with reduced growth. Furthermore, a highly mutated pfcrt allele from Cambodia (Cam734) conferred moderate chloroquine resistance and enhanced growth rates, when tested against wild-type pfcrt in co-culture competition assays. These three alleles mediated cross-resistance to amodiaquine, an antimalarial drug widely used in Africa. Each allele, along with the globally prevalent Dd2 and 7G8 alleles, rendered parasites more susceptible to lumefantrine, the partner drug used in the leading first-line artemisinin-based combination therapy. These data reveal ongoing region-specific evolution of PfCRT that impacts drug susceptibility and relative fitness in settings of mixed infections, and raise important considerations about optimal agents to treat chloroquine-resistant malaria.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.