ArticleNature microbiology2023
Chloroquine resistance evolution in Plasmodium falciparum is mediated by the putative amino acid transporter AAT1.
Article in Nature microbiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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56 citing papers in PubMed, 86 citations in OpenAlex.
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- Identification of genetic markers of quinine partial resistance in Plasmodium falciparum.Nature microbiology · 2026Article
- PfApiAT2 is a proline transporter essential for the transmission of Plasmodium falciparum by the mosquito vector.Nature communications · 2026Article
- Gain-of-function PfAAT1 mutations compensate for impaired PfCRT function inResearch square · 2026Article
- Structural and mechanistic insights into the inhibition of Plasmodium falciparum MDR1.Nature communications · 2026Article
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- Impact of intensive control on malaria population genomics under elimination settings in Southeast Asia.Nature microbiology · 2026Article
- National genomic profiling of Plasmodium falciparum antimalarial resistance in Zambian children participating in the 2018 malaria indicator survey.Scientific reports · 2026Article
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- Targeted Genomic Surveillance Unveils Genetic Variations Linked to Regional Malaria Drug Resistance Dynamics in India.Open forum infectious diseases · 2026Article
- Antimalarial drug resistance inParasitology · 2026Article
- hmmibd-rs: an enhanced hmmIBD implementation for parallelizable identity-by-descent detection from large-scale Plasmodium genomic data.Malaria journal · 2026Article
- PfApiAT2 is a proline transporter essential for the transmission ofResearch square · 2026Article
- Article
- PfApiAT2 is a proline transporter essential for the transmission ofbioRxiv : the preprint server for biology · 2026Article
- Major features of parasite adaptation revealed by genomes of Plasmodium falciparum population samples archived for over 50 years.Communications biology · 2026Article
- Molecular Markers of Antimalarial Drug Resistance in Plasmodium falciparum From Kumasi, Ghana, 2023.Tropical medicine & international health : TM & IH · 2026Article
- Targeted Sequencing Identifies SNPs Associated with Antimalarial Drug Resistance and the CSP Vaccine Antigen inInternational journal of molecular sciences · 2025Article
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28 authors at 9 institutions in 4 countries.
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Abstract
Malaria parasites break down host haemoglobin into peptides and amino acids in the digestive vacuole for export to the parasite cytoplasm for growth: interrupting this process is central to the mode of action of several antimalarial drugs. Mutations in the chloroquine (CQ) resistance transporter, pfcrt, located in the digestive vacuole membrane, confer CQ resistance in Plasmodium falciparum, and typically also affect parasite fitness. However, the role of other parasite loci in the evolution of CQ resistance is unclear. Here we use a combination of population genomics, genetic crosses and gene editing to demonstrate that a second vacuolar transporter plays a key role in both resistance and compensatory evolution. Longitudinal genomic analyses of the Gambian parasites revealed temporal signatures of selection on a putative amino acid transporter (pfaat1) variant S258L, which increased from 0% to 97% in frequency between 1984 and 2014 in parallel with the pfcrt1 K76T variant. Parasite genetic crosses then identified a chromosome 6 quantitative trait locus containing pfaat1 that is selected by CQ treatment. Gene editing demonstrated that pfaat1 S258L potentiates CQ resistance but at a cost of reduced fitness, while pfaat1 F313S, a common southeast Asian polymorphism, reduces CQ resistance while restoring fitness. Our analyses reveal hidden complexity in CQ resistance evolution, suggesting that pfaat1 may underlie regional differences in the dynamics of resistance evolution, and modulate parasite resistance or fitness by manipulating the balance between both amino acid and drug transport.
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