ArticleMolecular microbiology2012
The de novo and salvage pathways of GDP-mannose biosynthesis are both sufficient for the growth of bloodstream-form Trypanosoma brucei.
Article in Molecular microbiology, 2012. 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, 20 citations in OpenAlex.
- Hyperglycemia alters N-glycans on colon cancer cells through increased production of activated monosaccharides.Glycoconjugate journal · 2022Article
- L-fucose, a sugary regulator of antitumor immunity and immunotherapies.Molecular carcinogenesis · 2022Review
- Article
- Nucleotide sugar biosynthesis occurs in the glycosomes of procyclic and bloodstream form Trypanosoma brucei.PLoS neglected tropical diseases · 2021Article
- Article
- Proteomic analysis of glycosomes from Trypanosoma cruzi epimastigotes.Molecular and biochemical parasitology · 2019Article
- Gluconeogenesis using glycerol as a substrate in bloodstream-form Trypanosoma brucei.PLoS pathogens · 2018Article
- One pot synthesis of GDP-mannose by a multi-enzyme cascade for enzymatic assembly of lipid-linked oligosaccharides.Biotechnology and bioengineering · 2018Article
- Article
- Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.PLoS pathogens · 2015Article
- High-confidence glycosome proteome for procyclic form Trypanosoma brucei by epitope-tag organelle enrichment and SILAC proteomics.Journal of proteome research · 2014Article
- Discovery of two β-1,2-mannoside phosphorylases showing different chain-length specificities from Thermoanaerobacter sp. X-514.PloS one · 2014Article
- Metabolomics guides rational development of a simplified cell culture medium for drug screening against Trypanosoma brucei.Antimicrobial agents and chemotherapy · 2013Article
- Inhibition of nucleotide sugar transport in Trypanosoma brucei alters surface glycosylation.The Journal of biological chemistry · 2013Article
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
The sugar nucleotide GDP-mannose is essential for Trypanosoma brucei. Phosphomannose isomerase occupies a key position on the de novo pathway to GDP-mannose from glucose, just before intersection with the salvage pathway from free mannose. We identified the parasite phosphomannose isomerase gene, confirmed that it encodes phosphomannose isomerase activity and localized the endogenous enzyme to the glycosome. We also created a bloodstream-form conditional null mutant of phosphomannose isomerase to assess the relative roles of the de novo and salvage pathways of GDP-mannose biosynthesis. Phosphomannose isomerase was found to be essential for parasite growth. However, supplementation of the medium with low concentrations of mannose, including that found in human plasma, relieved this dependence. Therefore, we do not consider phosphomannose isomerase to be a viable drug target. We further established culture conditions where we can control glucose and mannose concentrations and perform steady-state [U-(13) C]-D-glucose labelling. Analysis of the isotopic sugar composition of the parasites variant surface glycoprotein synthesized in cells incubated in 5 mM [U-(13) C]-D-glucose in the presence and absence of unlabelled mannose showed that, under physiological conditions, about 80% of GDP-mannose synthesis comes from the de novo pathway and 20% from the salvage pathway.
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