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© Christine Schmitt, Sophie Goyard, Jean-Marc Panaud
Trypanosoma vivax - forme sanguine. Responsable de la trypanosomose animale ou Nagana.
Publication : PLoS biology

Glycerol suppresses glucose consumption in trypanosomes through metabolic contest.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in PLoS biology - 13 Aug 2021

Allmann S, Wargnies M, Plazolles N, Cahoreau E, Biran M, Morand P, Pineda E, Kulyk H, Asencio C, Villafraz O, Rivière L, Tetaud E, Rotureau B, Mourier A, Portais JC, Bringaud F,

Link to Pubmed [PMID] – 34388147

Link to DOI – 10.1371/journal.pbio.3001359

PLoS Biol 2021 Aug; 19(8): e3001359

Microorganisms must make the right choice for nutrient consumption to adapt to their changing environment. As a consequence, bacteria and yeasts have developed regulatory mechanisms involving nutrient sensing and signaling, known as “catabolite repression,” allowing redirection of cell metabolism to maximize the consumption of an energy-efficient carbon source. Here, we report a new mechanism named “metabolic contest” for regulating the use of carbon sources without nutrient sensing and signaling. Trypanosoma brucei is a unicellular eukaryote transmitted by tsetse flies and causing human African trypanosomiasis, or sleeping sickness. We showed that, in contrast to most microorganisms, the insect stages of this parasite developed a preference for glycerol over glucose, with glucose consumption beginning after the depletion of glycerol present in the medium. This “metabolic contest” depends on the combination of 3 conditions: (i) the sequestration of both metabolic pathways in the same subcellular compartment, here in the peroxisomal-related organelles named glycosomes; (ii) the competition for the same substrate, here ATP, with the first enzymatic step of the glycerol and glucose metabolic pathways both being ATP-dependent (glycerol kinase and hexokinase, respectively); and (iii) an unbalanced activity between the competing enzymes, here the glycerol kinase activity being approximately 80-fold higher than the hexokinase activity. As predicted by our model, an approximately 50-fold down-regulation of the GK expression abolished the preference for glycerol over glucose, with glucose and glycerol being metabolized concomitantly. In theory, a metabolic contest could be found in any organism provided that the 3 conditions listed above are met.

https://pubmed.ncbi.nlm.nih.gov/34388147