ArticleMolecular microbiology2009
The ethanolamine branch of the Kennedy pathway is essential in the bloodstream form of Trypanosoma brucei.
Article in Molecular microbiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Ethanolaminephosphate cytidylyltransferase is essential for survival, lipid homeostasis and stress tolerance in Leishmania major.PLoS pathogens · 2023Article
- Synthesis vs. salvage of ester- and ether-linked phosphatidylethanolamine in the intracellular protozoan pathogen Toxoplasma gondii.Communications biology · 2023Article
- The lipidome ofFrontiers in cellular and infection microbiology · 2022Article
- Lipid and fatty acid metabolism in trypanosomatids.Microbial cell (Graz, Austria) · 2021Review
- Article
- Drug effects on metabolic profiles of Schistosoma mansoni adult male parasites detected by 1H-NMR spectroscopy.PLoS neglected tropical diseases · 2020Article
- Mitochondrial sphingosine-1-phosphate lyase is essential for phosphatidylethanolamine synthesis and survival of Trypanosoma brucei.Scientific reports · 2020Article
- Phosphatidylcholine synthesis through cholinephosphate cytidylyltransferase is dispensable in Leishmania major.Scientific reports · 2019Article
- Overproduction of Phospholipids by the Kennedy Pathway Leads to Hypervirulence inFrontiers in microbiology · 2019Article
- The glycosomal alkyl-dihydroxyacetonephosphate synthase TbADS is essential for the synthesis of ether glycerophospholipids in procyclic trypanosomes.Experimental parasitology · 2018Article
- Discovery and Genetic Validation of Chemotherapeutic Targets for Chagas' Disease.Frontiers in cellular and infection microbiology · 2018Review
- Lipid analysis ofCell discovery · 2018Article
- Lipidomics and anti-trypanosomatid chemotherapy.Clinical and translational medicine · 2017Review
- Comparative sphingolipidomics of disease-causing trypanosomatids reveal unique lifecycle- and taxonomy-specific lipid chemistries.Scientific reports · 2017Article
- Phosphatidylserine synthase 2 and phosphatidylserine decarboxylase are essential for aminophospholipid synthesis in Trypanosoma brucei.Molecular microbiology · 2017Article
- Article
- The Glycerol-3-Phosphate Acyltransferase TbGAT is Dispensable for Viability and the Synthesis of Glycerolipids in Trypanosoma brucei.The Journal of eukaryotic microbiology · 2016Article
- Plasmenylethanolamine synthesis in Leishmania major.Molecular microbiology · 2016Article
- Phosphatidylethanolamine and phosphatidylcholine biosynthesis by the Kennedy pathway occurs at different sites in Trypanosoma brucei.Scientific reports · 2015Article
- The essential roles of cytidine diphosphate-diacylglycerol synthase in bloodstream form Trypanosoma brucei.Molecular microbiology · 2014Article
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3 authors.
Funding
Abstract
Phosphatidylethanolamine (GPEtn), a major phospholipid component of trypanosome membranes, is synthesized de novo from ethanolamine through the Kennedy pathway. Here the composition of the GPEtn molecular species in the bloodstream form of Trypanosoma brucei is determined, along with new insights into phospholipid metabolism, by in vitro and in vivo characterization of a key enzyme of the Kennedy pathway, the cytosolic ethanolamine-phosphate cytidylyltransferase (TbECT). Gene knockout indicates that TbECT is essential for growth and survival, thus highlighting the importance of the Kennedy pathway for the pathogenic stage of the African trypanosome. Phosphatiylserine decarboxylation, a potential salvage pathway, does not appear to be active in cultured bloodstream form T. brucei, and it is not upregulated even when the Kennedy pathway is disrupted. In vivo metabolic labelling and phospholipid composition analysis by ESI-MS/MS of the knockout cells confirmed a significant decrease in GPEtn species, as well as changes in the relative abundance of other phospholipid species. Reduction in GPEtn levels had a profound influence on the morphology of the mutants and it compromised mitochondrial structure and function, as well as glycosylphosphatidylinositol anchor biosynthesis. TbECT is therefore genetically validated as a potential drug target against the African trypanosome.
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