ArticleProceedings of the National Academy of Sciences of the United States of America2013
Plasmodium falciparum phosphoethanolamine methyltransferase is essential for malaria transmission.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 68 citations in OpenAlex.
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- Simple supplementation of serum-free medium produces gametocytes of Plasmodium falciparum that transmit to mosquitoes.Malaria journal · 2024Article
- Mass Spectrometry Imaging of In VitroBiomolecules · 2023Article
- Broad-Spectrum Inhibitors for Conserved Unique Phosphoethanolamine Methyltransferases in Parasitic Nematodes Possess Anthelmintic Efficacy.Antimicrobial agents and chemotherapy · 2023Article
- The human malaria parasiteProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Adapt or Die: Targeting Unique Transmission-Stage Biology for Malaria Elimination.Frontiers in cellular and infection microbiology · 2022Review
- Differential expression of calcium-dependent protein kinase 4, tubulin tyrosine ligase, and methyltransferase by xanthurenic acid-induced Babesia bovis sexual stages.Parasites & vectors · 2021Article
- Linking nutrient sensing and gene expression in Plasmodium falciparum blood-stage parasites.Molecular microbiology · 2021Review
- Erythrocyte sphingosine kinase regulates intraerythrocytic development of Plasmodium falciparum.Scientific reports · 2021Article
- Characterization ofFrontiers in cellular and infection microbiology · 2021Article
- Metabolic regulation of sexual commitment in Plasmodium falciparum.Current opinion in microbiology · 2020Review
- Review
- Vive la Différence: Exploiting the Differences between Rodent and Human Malarias.Trends in parasitology · 2020Review
- Docking predictions basedBMC chemistry · 2019Article
- Polyunsaturated fatty acids promoteBiology open · 2019Article
- Novel lactate dehydrogenase inhibitors with in vivo efficacy against Cryptosporidium parvum.PLoS pathogens · 2019Article
- Article
- Role of phospholipid synthesis in the development and differentiation of malaria parasites in the blood.The Journal of biological chemistry · 2018Review
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Authors and funding
16 authors at 6 institutions in 1 country.
Funding
Abstract
Efficient transmission of Plasmodium species between humans and Anopheles mosquitoes is a major contributor to the global burden of malaria. Gametocytogenesis, the process by which parasites switch from asexual replication within human erythrocytes to produce male and female gametocytes, is a critical step in malaria transmission and Plasmodium genetic diversity. Nothing is known about the pathways that regulate gametocytogenesis and only few of the current drugs that inhibit asexual replication are also capable of inhibiting gametocyte development and blocking malaria transmission. Here we provide genetic and pharmacological evidence indicating that the pathway for synthesis of phosphatidylcholine in Plasmodium falciparum membranes from host serine is essential for parasite gametocytogenesis and malaria transmission. Parasites lacking the phosphoethanolamine N-methyltransferase enzyme, which catalyzes the limiting step in this pathway, are severely altered in gametocyte development, are incapable of producing mature-stage gametocytes, and are not transmitted to mosquitoes. Chemical screening identified 11 inhibitors of phosphoethanolamine N-methyltransferase that block parasite intraerythrocytic asexual replication and gametocyte differentiation in the low micromolar range. Kinetic studies in vitro as well as functional complementation assays and lipid metabolic analyses in vivo on the most promising inhibitor NSC-158011 further demonstrated the specificity of inhibition. These studies set the stage for further optimization of NSC-158011 for development of a class of dual activity antimalarials to block both intraerythrocytic asexual replication and gametocytogenesis.
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