ArticleMolecular microbiology2006
The glycosylphosphatidylinositol (GPI) biosynthetic pathway of bloodstream-form Trypanosoma brucei is dependent on the de novo synthesis of inositol.
Article in Molecular microbiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 60 citations in OpenAlex.
- Article
- 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
- New insights in photodynamic inactivation of Leishmania amazonensis: A focus on lipidomics and resistance.PloS one · 2023Article
- Mucosal Infection with Unmasked Candida albicans Cells Impacts Disease Progression in a Host Niche-Specific Manner.Infection and immunity · 2022Article
- The lipidome ofFrontiers in cellular and infection microbiology · 2022Article
- Molecular characterization of stress tolerance genes associated with D. indicus strain under extreme environment conditions.Environmental geochemistry and health · 2021Article
- Inositol polyphosphate-protein interactions: Implications for microbial pathogenicity.Cellular microbiology · 2021Review
- Phosphatidylinositol synthesis, its selective salvage, and inter-regulation of anionic phospholipids in Toxoplasma gondii.Communications biology · 2020Article
- ITPK1 mediates the lipid-independent synthesis of inositol phosphates controlled by metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Blocking variant surface glycoprotein synthesis alters endoplasmic reticulum exit sites/Golgi homeostasis in Trypanosoma brucei.Traffic (Copenhagen, Denmark) · 2018Article
- Lipidomics and anti-trypanosomatid chemotherapy.Clinical and translational medicine · 2017Review
- 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
- Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.PLoS pathogens · 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 essential and non-essential protein kinases by a fusion PCR method for efficient production of transgenic Trypanosoma brucei.Molecular and biochemical parasitology · 2013Article
- Identification of a novel lipin homologue from the parasitic protozoan Trypanosoma brucei.BMC microbiology · 2013Article
- A class of 5-nitro-2-furancarboxylamides with potent trypanocidal activity against Trypanosoma brucei in vitro.Journal of medicinal chemistry · 2013Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In bloodstream-form Trypanosoma brucei (the causative agent of African sleeping sickness) the glycosylphosphatidylinositol (GPI) anchor biosynthetic pathway has been validated genetically and chemically as a drug target. The conundrum that GPI anchors could not be in vivo labelled with [3H]-inositol led us to hypothesize that de novo synthesis was responsible for supplying myo-inositol for phosphatidylinositol (PI) destined for GPI synthesis. The rate-limiting step of the de novo synthesis is the isomerization of glucose 6-phosphate to 1-D-myo-inositol-3-phosphate, catalysed by a 1-D-myo-inositol-3-phosphate synthase (INO1). When grown under non-permissive conditions, a conditional double knockout demonstrated that INO1 is an essential gene in bloodstream-form T. brucei. It also showed that the de novo synthesized myo-inositol is utilized to form PI, which is preferentially used in GPI biosynthesis. We also show for the first time that extracellular myo-inositol can in fact be used in GPI formation although to a limited extent. Despite this, extracellular inositol cannot compensate for the deletion of INO1. Supporting these results, there was no change in PI levels in the conditional double knockout cells grown under non-permissive conditions, showing that perturbation of growth is due to a specific lack of de novo synthesized myo-inositol and not a general inositol-less death. These results suggest that there is a distinction between de novo synthesized myo-inositol and that from the extracellular environment.
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