ArticleNature communications2024
Genome sequencing of Plasmodium malariae identifies continental segregation and mutations associated with reduced pyrimethamine susceptibility.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Tropism ofEmerging microbes & infections · 2026Article
- Identification of two genomic cryptotypes of Plasmodium malariae in Africa.PLoS neglected tropical diseases · 2026Article
- Population genomics of Plasmodium malariae from 4 African countries.JCI insight · 2026Article
- Malaria-GENOMAP: a web-based tool for exploring genomic variation of malaria parasites.Bioinformatics (Oxford, England) · 2026Article
- Synergistic activity of RSL3 and Pyrimethamine to inhibit the proliferation ofAntimicrobial agents and chemotherapy · 2025Article
- Ex Vivo Drug Susceptibility ofPathogens (Basel, Switzerland) · 2025Article
- Leveraging genomic insights from the neglected malaria parasites P. malariae and P. ovale using selective whole genome amplification (SWGA) approach.BMC genomics · 2025Article
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Authors and funding
16 authors.
Funding
Abstract
Plasmodium malariae parasites are widely observed across the tropics and sub-tropics. This slow-growing species, known to maintain chronic asymptomatic infections, has been associated with reduced antimalarial susceptibility. We analyse 251 P. malariae genomes from 28 countries, and leveraging 131,601 high-quality SNPs, demonstrate segregation of African and Asian isolates. Signals of recent evolutionary selection were identified in genes encoding putative surface proteins (pmmsp1) and putative erythrocyte invasion proteins (pmdpap3, pmrbp2, pmnif4). Amino acid substitutions were identified in orthologs of genes associated with antimalarial susceptibility including 2 amino acid substitutions in pmdhfr aligning with pyrimethamine resistance mutations in P. falciparum. Additionally, we characterise pmdhfr mutation F57L and demonstrate its involvement in reduced susceptibility to pyrimethamine in an in vitro parasite assay. We validate CRISPR-Cas9 mediated ortholog replacement in P. knowlesi parasites to determine the function of pmdhfr mutations and demonstrate that circulating pmdhfr genotypes are less susceptible to pyrimethamine.
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