ArticleScientific reports2018
Heterologous Expression of a Novel Drug Transporter from the Malaria Parasite Alters Resistance to Quinoline Antimalarials.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 26 citations in OpenAlex.
- Gain-of-function PfAAT1 mutations compensate for impaired PfCRT function inResearch square · 2026Article
- Elucidating the link between NS-SNP-Induced protein conformational changes and drug resistance in Klebsiella pneumoniae.Archives of microbiology · 2026Article
- Tracking Plasmodium falciparum antimalarial resistance markers during a malaria pre-elimination period in the Pacific coast of South America.Scientific reports · 2025Article
- Strong positive selection biases identity-by-descent-based inferences of recent demography and population structure in Plasmodium falciparum.Nature communications · 2024Article
- Malaria surveillance reveals parasite relatedness, signatures of selection, and correlates of transmission across Senegal.Nature communications · 2023Article
- Strong Positive Selection Biases Identity-By-Descent-Based Inferences of Recent Demography and Population Structure inbioRxiv : the preprint server for biology · 2023Article
- Chloroquine resistance evolution in Plasmodium falciparum is mediated by the putative amino acid transporter AAT1.Nature microbiology · 2023Article
- Genetic mapping of determinants in drug resistance, virulence, disease susceptibility, and interaction of host-rodent malaria parasites.Parasitology international · 2022Review
- Article
- The Transporter-Mediated Cellular Uptake and Efflux of Pharmaceutical Drugs and Biotechnology Products: How and Why Phospholipid Bilayer Transport Is Negligible in Real Biomembranes.Molecules (Basel, Switzerland) · 2021Review
- The natural function of the malaria parasite's chloroquine resistance transporter.Nature communications · 2020Article
- Choline Chloride-Based Deep Eutectic Systems in Sequential Friedländer Reaction and Palladium-Catalyzed spACS omega · 2019Article
- Novel Combinations of Agents Targeting Translation That Synergistically Inhibit Fungal Pathogens.Frontiers in microbiology · 2018Article
- Extreme Osmotolerance and Halotolerance in Food-Relevant Yeasts and the Role of Glycerol-Dependent Cell Individuality.Frontiers in microbiology · 2018Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Antimalarial drug resistance hampers effective malaria treatment. Critical SNPs in a particular, putative amino acid transporter were recently linked to chloroquine (CQ) resistance in malaria parasites. Here, we show that this conserved protein (PF3D7_0629500 in Plasmodium falciparum; AAT1 in P. chabaudi) is a structural homologue of the yeast amino acid transporter Tat2p, which is known to mediate quinine uptake and toxicity. Heterologous expression of PF3D7_0629500 in yeast produced CQ hypersensitivity, coincident with increased CQ uptake. PF3D7_0629500-expressing cultures were also sensitized to related antimalarials; amodiaquine, mefloquine and particularly quinine. Drug sensitivity was reversed by introducing a SNP linked to CQ resistance in the parasite. Like Tat2p, PF3D7_0629500-dependent quinine hypersensitivity was suppressible with tryptophan, consistent with a common transport mechanism. A four-fold increase in quinine uptake by PF3D7_0629500 expressing cells was abolished by the resistance SNP. The parasite protein localised primarily to the yeast plasma membrane. Its expression varied between cells and this heterogeneity was used to show that high-expressing cell subpopulations were the most drug sensitive. The results reveal that the PF3D7_0629500 protein can determine the level of sensitivity to several major quinine-related antimalarials through an amino acid-inhibitable drug transport function. The potential clinical relevance is discussed.
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