Combining reverse genetics and nuclear magnetic resonance-based metabolomics unravels trypanosome-specific metabolic pathways

Molecular Microbiology
F BringaudMuriel Mazet

Abstract

Numerous eukaryotes have developed specific metabolic traits that are not present in extensively studied model organisms. For instance, the procyclic insect form of Trypanosoma brucei, a parasite responsible for sleeping sickness in its mammalian-specific bloodstream form, metabolizes glucose into excreted succinate and acetate through pathways with unique features. Succinate is primarily produced from glucose-derived phosphoenolpyruvate in peroxisome-like organelles, also known as glycosomes, by a soluble NADH-dependent fumarate reductase only described in trypanosomes so far. Acetate is produced in the mitochondrion of the parasite from acetyl-CoA by a CoA-transferase, which forms an ATP-producing cycle with succinyl-CoA synthetase. The role of this cycle in ATP production was recently demonstrated in procyclic trypanosomes and has only been proposed so far for anaerobic organisms, in addition to trypanosomatids. We review how nuclear magnetic resonance spectrometry can be used to analyze the metabolic network perturbed by deletion (knockout) or downregulation (RNAi) of the candidate genes involved in these two particular metabolic pathways of procyclic trypanosomes. The role of succinate and acetate production in trypanosome...Continue Reading

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Citations

Sep 24, 2015·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Philippe SolanoJérémy Bouyer
Sep 29, 2015·Evidence-based Complementary and Alternative Medicine : ECAM·Zhonghuang LiZhongqiu Liu
Jun 4, 2016·International Journal of Molecular Sciences·Jun HongJianxin Shi
Mar 9, 2018·Proteomics. Clinical Applications·Natalia Tiberti, Jean-Charles Sanchez
Jun 20, 2017·F1000Research·Terry K SmithLuisa M Figueiredo
Dec 18, 2018·PLoS Pathogens·Marion WargniesFrédéric Bringaud
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Jan 11, 2016·Molecular Microbiology·Jitka ŠtáfkováJan Tachezy
Aug 14, 2021·PLoS Biology·Stefan AllmannFrédéric Bringaud
Dec 3, 2021·PLoS Pathogens·Frédéric BringaudEmmanuel Tetaud

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