ArticleMolecular microbiology2014
The essential roles of cytidine diphosphate-diacylglycerol synthase in bloodstream form Trypanosoma brucei.
Article in Molecular microbiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- The mitochondrial proteome of diplonemids: from conventional pathways to eccentric RNA editing and transcript processing.BMC genomics · 2025Article
- Identification and characterization of archaeal-type FAD synthase as a novel tractable drug target from the parasitic protozoamSphere · 2024Article
- Investigating mouse hepatic lipidome dysregulation following exposure to emerging per- and polyfluoroalkyl substances (PFAS).Chemosphere · 2024Article
- How much (ATP) does it cost to build a trypanosome? A theoretical study on the quantity of ATP needed to maintain and duplicate a bloodstream-form Trypanosoma brucei cell.PLoS pathogens · 2023Article
- Article
- Phosphatidylinositol synthesis, its selective salvage, and inter-regulation of anionic phospholipids in Toxoplasma gondii.Communications biology · 2020Article
- The phosphoinositide regulatory network in Trypanosoma brucei: Implications for cell-wide regulation in eukaryotes.PLoS neglected tropical diseases · 2020Review
- CDP-Diacylglycerol Synthases (CDS): Gateway to Phosphatidylinositol and Cardiolipin Synthesis.Frontiers in cell and developmental biology · 2020Review
- Lipid analysis ofCell discovery · 2018Article
- Cross-species complementation of bacterial- and eukaryotic-type cardiolipin synthases.Microbial cell (Graz, Austria) · 2017Article
- Phosphatidylserine synthase 2 and phosphatidylserine decarboxylase are essential for aminophospholipid synthesis in Trypanosoma brucei.Molecular microbiology · 2017Article
- Two phylogenetically and compartmentally distinct CDP-diacylglycerol synthases cooperate for lipid biogenesis inThe Journal of biological chemistry · 2017Article
- The Glycerol-3-Phosphate Acyltransferase TbGAT is Dispensable for Viability and the Synthesis of Glycerolipids in Trypanosoma brucei.The Journal of eukaryotic microbiology · 2016Article
- Trypanosoma brucei Bloodstream Forms Depend upon Uptake of myo-Inositol for Golgi Complex Phosphatidylinositol Synthesis and Normal Cell Growth.Eukaryotic cell · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Lipid metabolism in Trypanosoma brucei, the causative agent of African sleeping sickness, differs from its human host in several fundamental ways. This has lead to the validation of a plethora of novel drug targets, giving hope of novel chemical intervention against this neglected disease. Cytidine diphosphate diacylglycerol (CDP-DAG) is a central lipid intermediate for several pathways in both prokaryotes and eukaryotes, being produced by CDP-DAG synthase (CDS). However, nothing is known about the single T. brucei CDS gene (Tb927.7.220/EC 2.7.7.41) or its activity. In this study we show TbCDS is functional by complementation of a non-viable yeast CDS null strain and that it is essential in the bloodstream form of the parasite via a conditional knockout. The TbCDS conditional knockout showed morphological changes including a cell-cycle arrest due in part to kinetoplast segregation defects. Biochemical phenotyping of TbCDS conditional knockout showed drastically altered lipid metabolism where reducing levels of phosphatidylinositol detrimentally impacted on glycoylphosphatidylinositol biosynthesis. These studies also suggest that phosphatidylglycerol synthesized via the phosphatidylglycerol-phosphate synthase is not synthesized from CDP-DAG, as was previously thought. TbCDS was shown to localized the ER and Golgi, probably to provide CDP-DAG for the phosphatidylinositol synthases.
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