ArticleThe Biochemical journal2006
Phosphatidylinositol synthesis is essential in bloodstream form Trypanosoma brucei.
Article in The Biochemical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 66 citations in OpenAlex.
- Mass spectrometry-based metabolomics uncovers distinct metabolic signatures and potential therapeutic targets in Plasmodium knowlesi.PloS one · 2025Article
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- The lipidome ofFrontiers in cellular and infection microbiology · 2022Article
- 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
- Phosphoinositide signaling and regulation in Trypanosoma brucei: Specialized functions in a protozoan pathogen.PLoS pathogens · 2020Review
- Article
- Tamoxifen inhibits the biosynthesis of inositolphosphorylceramide in Leishmania.International journal for parasitology. Drugs and drug resistance · 2018Article
- Lipid analysis ofCell discovery · 2018Article
- Lipidomics and anti-trypanosomatid chemotherapy.Clinical and translational medicine · 2017Review
- Zeamide, a Glycosylinositol Phosphorylceramide with the Novel Core Arap(1β→6)Ins Motif from the Marine Sponge Svenzea zeai.Molecules (Basel, Switzerland) · 2017Article
- RFT1 Protein Affects Glycosylphosphatidylinositol (GPI) Anchor Glycosylation.The Journal of biological chemistry · 2017Article
- InsP3 Signaling in Apicomplexan Parasites.Current topics in medicinal chemistry · 2017Review
- The Glycerol-3-Phosphate Acyltransferase TbGAT is Dispensable for Viability and the Synthesis of Glycerolipids in Trypanosoma brucei.The Journal of eukaryotic microbiology · 2016Article
- Lipid topogenesis--35years on.Biochimica et biophysica acta · 2016Review
- Chemogenetic Characterization of Inositol Phosphate Metabolic Pathway Reveals Druggable Enzymes for Targeting Kinetoplastid Parasites.Cell chemical biology · 2016Article
- Trypanosoma brucei Bloodstream Forms Depend upon Uptake of myo-Inositol for Golgi Complex Phosphatidylinositol Synthesis and Normal Cell Growth.Eukaryotic cell · 2015Article
- The essential roles of cytidine diphosphate-diacylglycerol synthase in bloodstream form Trypanosoma brucei.Molecular microbiology · 2014Article
- Lipid synthesis in protozoan parasites: a comparison between kinetoplastids and apicomplexans.Progress in lipid research · 2013Review
- Identification of a novel lipin homologue from the parasitic protozoan Trypanosoma brucei.BMC microbiology · 2013Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
PI (phosphatidylinositol) is a ubiquitous eukaryotic phospholipid which serves as a precursor for messenger molecules and GPI (glycosylphosphatidylinositol) anchors. PI is synthesized either de novo or by head group exchange by a PIS (PI synthase). The synthesis of GPI anchors has previously been validated both genetically and chemically as a drug target in Trypanosoma brucei, the causative parasite of African sleeping sickness. However, nothing is known about the synthesis of PI in this organism. Database mining revealed a putative TbPIS gene in the T. brucei genome and by recombinant expression and characterization it was shown to encode a catalytically active PIS, with a high specificity for myo-inositol. Immunofluorescence revealed that in T. brucei, PIS is found in both the endoplasmic reticulum and Golgi. We created a conditional double knockout of TbPIS in the bloodstream form of T. brucei, which when grown under non-permissive conditions, clearly showed that TbPIS is an essential gene. In vivo labelling of these conditional double knockout cells confirmed this result, showing a decrease in the amount of PI formed by the cells when grown under non-permissive conditions. Furthermore, quantitative and qualitative analysis by GLC-MS and ESI-MS/MS (electrospray ionization MS/MS) respectively showed a significant decrease (70%) in cellular PI, which appears to affect all major PI species equally. A consequence of this fall in PI level is a knock-on reduction in GPI biosynthesis which is essential for the parasite's survival. The results presented here show that PI synthesis is essential for bloodstream form T. brucei, and to our knowledge this is the first report of the dependence on PI synthesis of a protozoan parasite by genetic validation.
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