ArticlePLoS pathogens2020
Insights into the intracellular localization, protein associations and artemisinin resistance properties of Plasmodium falciparum K13.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 85 citations in OpenAlex.
- Identification of genetic markers of quinine partial resistance in Plasmodium falciparum.Nature microbiology · 2026Article
- Experimental evolution and functional genetics identify KIC1 as a determinant of reduced artemisinin susceptibility in BangladeshibioRxiv : the preprint server for biology · 2026Article
- Identification of an Orally Efficacious Imidazo[4,5-Journal of medicinal chemistry · 2026Article
- Cellular and molecular basis of PfCoronin function in artemisinin resistance in Plasmodium falciparum.Nature communications · 2026Article
- Double Mutations inbioRxiv : the preprint server for biology · 2026Article
- High throughput quantitative tracking ofbioRxiv : the preprint server for biology · 2026Article
- Fluorescence-based bioassay for the detection of changes in mitochondrial physiology during artemisinin-induced growth arrest of blood-stage Plasmodium falciparum.Scientific reports · 2025Article
- Safeguarding artemisinin: integrating bioproduction innovation and resistance management for malaria eradication.Malaria journal · 2025Review
- Characterization of β-Carboline Derivatives Reveals a High Barrier to Resistance and Potent Activity against Ring-Stage and DHA-Induced DormantACS infectious diseases · 2025Article
- Identifying a next-generation antimalarial trioxolane in a landscape of artemisinin partial resistance.Science advances · 2025Article
- Vesicular mechanisms of drug resistance in apicomplexan parasites.Microbiology and molecular biology reviews : MMBR · 2025Review
- Artemisinin-resistant malaria.Clinical microbiology reviews · 2024Review
- Population genomics and transcriptomics of Plasmodium falciparum in Cambodia and Vietnam uncover key components of the artemisinin resistance genetic background.Nature communications · 2024Article
- Artemisinin-resistant Plasmodium falciparum Kelch13 mutant proteins display reduced heme-binding affinity and decreased artemisinin activation.Communications biology · 2024Article
- Indigenous emergence and spread ofAntimicrobial agents and chemotherapy · 2024Article
- Impact of different mutations on Kelch13 protein levels, ART resistance, and fitness cost inmBio · 2024Article
- Emergence, transmission dynamics and mechanisms of artemisinin partial resistance in malaria parasites in Africa.Nature reviews. Microbiology · 2024Review
- tRNA modification reprogramming contributes to artemisinin resistance in Plasmodium falciparum.Nature microbiology · 2024Article
- Metabolic changes that allowFrontiers in parasitology · 2024Article
- Structures revealing mechanisms of resistance and collateral sensitivity of Plasmodium falciparum to proteasome inhibitors.Nature communications · 2023Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 4 countries.
Funding
Abstract
The emergence of artemisinin (ART) resistance in Plasmodium falciparum intra-erythrocytic parasites has led to increasing treatment failure rates with first-line ART-based combination therapies in Southeast Asia. Decreased parasite susceptibility is caused by K13 mutations, which are associated clinically with delayed parasite clearance in patients and in vitro with an enhanced ability of ring-stage parasites to survive brief exposure to the active ART metabolite dihydroartemisinin. Herein, we describe a panel of K13-specific monoclonal antibodies and gene-edited parasite lines co-expressing epitope-tagged versions of K13 in trans. By applying an analytical quantitative imaging pipeline, we localize K13 to the parasite endoplasmic reticulum, Rab-positive vesicles, and sites adjacent to cytostomes. These latter structures form at the parasite plasma membrane and traffic hemoglobin to the digestive vacuole wherein artemisinin-activating heme moieties are released. We also provide evidence of K13 partially localizing near the parasite mitochondria upon treatment with dihydroartemisinin. Immunoprecipitation data generated with K13-specific monoclonal antibodies identify multiple putative K13-associated proteins, including endoplasmic reticulum-resident molecules, mitochondrial proteins, and Rab GTPases, in both K13 mutant and wild-type isogenic lines. We also find that mutant K13-mediated resistance is reversed upon co-expression of wild-type or mutant K13. These data help define the biological properties of K13 and its role in mediating P. falciparum resistance to ART treatment.
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Registered trials
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