ArticleNature communications2021
The apicoplast link to fever-survival and artemisinin-resistance in the malaria parasite.
Article in Nature communications, 2021. 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, 62 citations in OpenAlex.
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- A Multidimensional Analysis of the Bimodal Piperaquine Response inbioRxiv : the preprint server for biology · 2026Article
- Characterisation of the thermal and non-thermal stress conditions that activate the Plasmodium falciparum AP2-HS-dependent heat-shock response.PLoS pathogens · 2026Article
- Physiological febrile heat stress increases cytoadhesion through increased protein trafficking ofeLife · 2026Article
- Integrative genomics ofbioRxiv : the preprint server for biology · 2026Article
- Large-Scale Mutagenesis Screening for Genetic Determinants of Plasmodium falciparum Sexual Development.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Phenotypic screens reveal Plasmodium falciparum genetic factors associated with infection of sickle-trait cells.Blood cells, molecules & diseases · 2025Article
- Evolutionary Trajectory ofBiomedicines · 2025Review
- Epigenetically conferred ring-stage survival in Plasmodium falciparum against artemisinin treatment.Nature communications · 2025Article
- Essential role for PfHSP40 in asexual replication and thermotolerance of malaria parasites.PLoS pathogens · 2025Article
- A chaperonin complex regulates organelle proteostasis in malaria parasites.PLoS pathogens · 2025Article
- The essential genome ofScience (New York, N.Y.) · 2025Article
- Emerging trends and new developments in global research on artemisinin and its derivatives.Heliyon · 2025Article
- Genetic factors regulating Plasmodium falciparum gametocytogenesis identified by phenotypic screens.Scientific reports · 2024Article
- 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
- Therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Arba Minch Zuria District, Gamo Zone, Southwest Ethiopia.Malaria journal · 2024Article
- tRNA modification reprogramming contributes to artemisinin resistance in Plasmodium falciparum.Nature microbiology · 2024Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
The emergence and spread of Plasmodium falciparum parasites resistant to front-line antimalarial artemisinin-combination therapies (ACT) threatens to erase the considerable gains against the disease of the last decade. Here, we develop a large-scale phenotypic screening pipeline and use it to carry out a large-scale forward-genetic phenotype screen in P. falciparum to identify genes allowing parasites to survive febrile temperatures. Screening identifies more than 200 P. falciparum mutants with differential responses to increased temperature. These mutants are more likely to be sensitive to artemisinin derivatives as well as to heightened oxidative stress. Major processes critical for P. falciparum tolerance to febrile temperatures and artemisinin include highly essential, conserved pathways associated with protein-folding, heat shock and proteasome-mediated degradation, and unexpectedly, isoprenoid biosynthesis, which originated from the ancestral genome of the parasite's algal endosymbiont-derived plastid, the apicoplast. Apicoplast-targeted genes in general are upregulated in response to heat shock, as are other Plasmodium genes with orthologs in plant and algal genomes. Plasmodium falciparum parasites appear to exploit their innate febrile-response mechanisms to mediate resistance to artemisinin. Both responses depend on endosymbiont-derived genes in the parasite's genome, suggesting a link to the evolutionary origins of Plasmodium parasites in free-living ancestors.
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