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- Title
Glycerol suppresses glucose consumption in trypanosomes through metabolic contest.
- Authors
Allmann, Stefan; Wargnies, Marion; Plazolles, Nicolas; Cahoreau, Edern; Biran, Marc; Morand, Pauline; Pineda, Erika; Kulyk, Hanna; Asencio, Corinne; Villafraz, Oriana; Rivière, Loïc; Tetaud, Emmanuel; Rotureau, Brice; Mourier, Arnaud; Portais, Jean-Charles; Bringaud, Frédéric
- Abstract
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. This study shows that Trypanosomes use a "metabolic contest" for the regulation of nutrient utilization based on the competition between two enzymes for a common substrate, instead of the well known "catabolite repression" used by most microorganisms.
- Subjects
GLUCOSE; CATABOLITE repression; AFRICAN trypanosomiasis; TSETSE-flies; GLUCOKINASE
- Publication
PLoS Biology, 2021, Vol 19, Issue 8, p1
- ISSN
1544-9173
- Publication type
Article
- DOI
10.1371/journal.pbio.3001359