ArticleNature communications2020
Genetic screens reveal a central role for heme metabolism in artemisinin susceptibility.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 74 citations in OpenAlex.
- Integrated Proteomic Screening Reveals Heme Enzyme Depletion Induces Cyst-like Vacuole Formation inInternational journal of molecular sciences · 2026Article
- Is heme metabolism a promising drug target in Toxoplasma gondii?PLoS pathogens · 2026Article
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- Advancements in CRISPR-Cas Systems for Genome Editing towards Eradication of Human Microbial Pathogens.Molecular biotechnology · 2026Review
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- A genome-wide CRISPR screen identifies GRA38 as a key regulator of lipid homeostasis during Toxoplasma gondii adaptation to lipid-rich conditions.Nature communications · 2025Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- Dissecting apicoplast functions through continuous cultivation of Toxoplasma gondii devoid of the organelle.Nature communications · 2025Article
- The essential genome ofScience (New York, N.Y.) · 2025Article
- Iron-mediated post-transcriptional regulation in Toxoplasma gondii.PLoS pathogens · 2025Article
- A scalable CRISPR-Cas9 gene editing system facilitates CRISPR screens in the malaria parasite Plasmodium berghei.Nucleic acids research · 2025Article
- The F204S mutation in adrenodoxin oxidoreductase drives salinomycin resistance in Eimeria tenella.Veterinary research · 2024Article
- Artemisinin-resistant Plasmodium falciparum Kelch13 mutant proteins display reduced heme-binding affinity and decreased artemisinin activation.Communications biology · 2024Article
- CRISPR screens identify genes essential formBio · 2024Article
- CRISPR-based functional profiling of the Toxoplasma gondii genome during acute murine infection.Nature microbiology · 2024Article
- SPARK regulates AGC kinases central to theeLife · 2024Article
- Review
- SPARK regulates AGC kinases central to thebioRxiv : the preprint server for biology · 2024Article
- Transforming the CRISPR/dCas9-based gene regulation technique into a forward screening tool iniScience · 2024Article
- Metabolic plasticity, essentiality and therapeutic potential of ribose-5-phosphate synthesis in Toxoplasma gondii.Nature communications · 2024Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
Artemisinins have revolutionized the treatment of Plasmodium falciparum malaria; however, resistance threatens to undermine global control efforts. To broadly explore artemisinin susceptibility in apicomplexan parasites, we employ genome-scale CRISPR screens recently developed for Toxoplasma gondii to discover sensitizing and desensitizing mutations. Using a sublethal concentration of dihydroartemisinin (DHA), we uncover the putative transporter Tmem14c whose disruption increases DHA susceptibility. Screens performed under high doses of DHA provide evidence that mitochondrial metabolism can modulate resistance. We show that disrupting a top candidate from the screens, the mitochondrial protease DegP2, lowers porphyrin levels and decreases DHA susceptibility, without significantly altering parasite fitness in culture. Deleting the homologous gene in P. falciparum, PfDegP, similarly lowers heme levels and DHA susceptibility. These results expose the vulnerability of heme metabolism to genetic perturbations that can lead to increased survival in the presence of DHA.
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Registered trials
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