ArticleCell chemical biology2022
The Plasmodium falciparum ABC transporter ABCI3 confers parasite strain-dependent pleiotropic antimalarial drug resistance.
Article in Cell chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 27 citations in OpenAlex.
- Malaria and cancer: common features and interactions.Trends in parasitology · 2026Review
- Identification of genetic markers of quinine partial resistance in Plasmodium falciparum.Nature microbiology · 2026Article
- Paclitaxel-induced tubulin dysfunction stalls parasite development: synergistic potential with artemisinin against resistant strains.Microbiology spectrum · 2026Article
- Exploration and Characterization of the Antimalarial Activity of Pyrimidine-2,4-Diamines for which Resistance is Mediated by the ABCI3 Transporter.ChemMedChem · 2026Article
- Heme processing in the malaria parasite, Plasmodium falciparum: a time-dependent basal-level analysis.Communications biology · 2025Article
- PfATP2 is a flippase on the Plasmodium falciparum surface that is important for growth and influences parasite sensitivity to antiplasmodial compounds.PLoS pathogens · 2025Article
- Plasmodiumfalciparum protein kinase 6 and hemozoin formation are inhibited by a type II human kinase inhibitor exhibiting antimalarial activity.Cell chemical biology · 2025Article
- Mapping the genomic landscape of multidrug resistance inScience advances · 2023Article
- Susceptibility of Ugandan Plasmodium falciparum Isolates to the Antimalarial Drug Pipeline.Microbiology spectrum · 2023Article
- Human Polo-like Kinase Inhibitors as Antiplasmodials.ACS infectious diseases · 2023Article
- Inhibitors of ApiAP2 protein DNA binding exhibit multistage activity against Plasmodium parasites.PLoS pathogens · 2022Article
- A G358S mutation in the Plasmodium falciparum NaNature communications · 2022Article
- PMRT1, amBio · 2022Article
- Updated List of Transport Proteins inFrontiers in cellular and infection microbiology · 2022Review
- Review
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Authors and funding
33 authors at 11 institutions in 4 countries.
Funding
Abstract
Widespread Plasmodium falciparum resistance to first-line antimalarials underscores the vital need to develop compounds with novel modes of action and identify new druggable targets. Here, we profile five compounds that potently inhibit P. falciparum asexual blood stages. Resistance selection studies with three carboxamide-containing compounds, confirmed by gene editing and conditional knockdowns, identify point mutations in the parasite transporter ABCI3 as the primary mediator of resistance. Selection studies with imidazopyridine or quinoline-carboxamide compounds also yield changes in ABCI3, this time through gene amplification. Imidazopyridine mode of action is attributed to inhibition of heme detoxification, as evidenced by cellular accumulation and heme fractionation assays. For the copy-number variation-selecting imidazopyridine and quinoline-carboxamide compounds, we find that resistance, manifesting as a biphasic concentration-response curve, can independently be mediated by mutations in the chloroquine resistance transporter PfCRT. These studies reveal the interconnectedness of P. falciparum transporters in overcoming drug pressure in different parasite strains.
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