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Glycerol suppresses glucose consumption in trypanosomes through metabolic contest.

Authors :
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
Source :
PLoS biology [PLoS Biol] 2021 Aug 13; Vol. 19 (8), pp. e3001359. Date of Electronic Publication: 2021 Aug 13 (Print Publication: 2021).
Publication Year :
2021

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.<br />Competing Interests: The authors have declared that no competing interests exist.

Details

Language :
English
ISSN :
1545-7885
Volume :
19
Issue :
8
Database :
MEDLINE
Journal :
PLoS biology
Publication Type :
Academic Journal
Accession number :
34388147
Full Text :
https://doi.org/10.1371/journal.pbio.3001359