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The ethanolamine branch of the Kennedy pathway is essential in the bloodstream form of Trypanosoma brucei
Article first published online: 23 JUN 2009
© 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Ltd
Volume 73, Issue 5, pages 826–843, September 2009
How to Cite
Gibellini, F., Hunter, W. N. and Smith, T. K. (2009), The ethanolamine branch of the Kennedy pathway is essential in the bloodstream form of Trypanosoma brucei. Molecular Microbiology, 73: 826–843. doi: 10.1111/j.1365-2958.2009.06764.x
- Issue published online: 24 AUG 2009
- Article first published online: 23 JUN 2009
- Accepted 1 June, 2009.
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.