ArticleProceedings of the National Academy of Sciences of the United States of America2002
Galactose metabolism is essential for the African sleeping sickness parasite Trypanosoma brucei.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 104 citations in OpenAlex.
- Molecular characterisation of Entamoeba histolytica UDP-glucose 4-epimerase, an enzyme able to provide building blocks for cyst wall formation.PLoS neglected tropical diseases · 2023Article
- Targeted protein degradation might present a novel therapeutic approach in the fight against African trypanosomiasis.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2023Article
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- Nucleotide sugar biosynthesis occurs in the glycosomes of procyclic and bloodstream form Trypanosoma brucei.PLoS neglected tropical diseases · 2021Article
- Association of UDP-galactose-4-epimerase with milk protein concentration in the Chinese Holstein population.Asian-Australasian journal of animal sciences · 2020Article
- Basal Body Protein TbSAF1 Is Required for Microtubule Quartet Anchorage to the Basal Bodies inmBio · 2020Article
- Structural basis for broad substrate specificity of UDP-glucose 4-epimerase in the human milk oligosaccharide catabolic pathway of Bifidobacterium longum.Scientific reports · 2019Article
- Gluconeogenesis using glycerol as a substrate in bloodstream-form Trypanosoma brucei.PLoS pathogens · 2018Article
- UDP-glycosyltransferase genes in trypanosomatid genomes have diversified independently to meet the distinct developmental needs of parasite adaptations.BMC evolutionary biology · 2018Article
- Discovery and Genetic Validation of Chemotherapeutic Targets for Chagas' Disease.Frontiers in cellular and infection microbiology · 2018Review
- Diglycosyl diselenides alter redox homeostasis and glucose consumption of infective African trypanosomes.International journal for parasitology. Drugs and drug resistance · 2017Article
- A Gene of the β3-Glycosyltransferase Family Encodes N-Acetylglucosaminyltransferase II Function in Trypanosoma brucei.The Journal of biological chemistry · 2016Article
- GMP synthase is essential for viability and infectivity of Trypanosoma brucei despite a redundant purine salvage pathway.Molecular microbiology · 2015Article
- A quaternary mechanism enables the complex biological functions of octameric human UDP-glucose pyrophosphorylase, a key enzyme in cell metabolism.Scientific reports · 2015Article
- Identification of a glycosylphosphatidylinositol anchor-modifying β1-3 galactosyltransferase in Trypanosoma brucei.Glycobiology · 2015Article
- UDP-galactose 4'-epimerase from the liver fluke, Fasciola hepatica: biochemical characterization of the enzyme and identification of inhibitors.Parasitology · 2015Article
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- The essential roles of cytidine diphosphate-diacylglycerol synthase in bloodstream form Trypanosoma brucei.Molecular microbiology · 2014Article
- Genetic validation of Trypanosoma brucei glutathione synthetase as an essential enzyme.Eukaryotic cell · 2014Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The tsetse fly-transmitted protozoan parasite Trypanosoma brucei is the causative agent of human African sleeping sickness and the cattle disease Nagana. The bloodstream form of the parasite uses a dense cell-surface coat of variant surface glycoprotein to escape the innate and adaptive immune responses of the mammalian host and a highly glycosylated transferrin receptor to take up host transferrin, an essential growth factor. These glycoproteins, as well as other flagellar pocket, endosomal, and lysosomal glycoproteins, are known to contain galactose. The parasite is unable to take up galactose, suggesting that it may depend on the action of UDP-glucose 4'-epimerase for the conversion of UDP-Glc to UDP-Gal and subsequent incorporation of galactose into glycoconjugates via UDP-Gal-dependent galactosyltransferases. In this paper, we describe the cloning of T. brucei galE, encoding T. brucei UDP-Glc-4'-epimerase, and functional characterization by complementation of a galE-deficient Escherichia coli mutant and enzymatic assay of recombinant protein. A tetracycline-inducible conditional galE null mutant of T. brucei was created using a transgenic parasite expressing the TETR tetracycline repressor protein gene. Withdrawal of tetracycline led to a cessation of cell division and substantial cell death, demonstrating that galactose metabolism in T. brucei proceeds via UDP-Glc-4'-epimerase and is essential for parasite growth. After several days without tetracycline, cultures spontaneously recovered. These cells were shown to have undergone a genetic rearrangement that deleted the TETR gene. The results show that enzymes and transporters involved in galactose metabolism may be considered as potential therapeutic targets against African trypanosomiasis.
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