Glycerol suppresses glucose consumption in trypanosomes through metabolic contest

PLoS Biol. 2021 Aug 13;19(8):e3001359. doi: 10.1371/journal.pbio.3001359. eCollection 2021 Aug.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Cell Line
  • Glycerol / metabolism*
  • Glycerol Kinase / metabolism*
  • Hexokinase / metabolism*
  • Microbodies / enzymology*
  • Trypanosoma brucei brucei / metabolism*


  • Adenosine Triphosphate
  • Hexokinase
  • Glycerol Kinase
  • Glycerol

Grants and funding

FB's team is supported by the Centre National de la Recherche Scientifique (CNRS, (financial support for consumables and salary of permanent positions), the Université de Bordeaux ( (financial support for consumables and salary of permanent positions), the Agence National de Recherche (ANR, through the grants GLYCONOV (grant number ANR-15-CE15-0025-01) and ADIPOTRYP (grant number ANR19-CE15-0004-01) (financial support for consumables and PM and EP salary) and the Laboratoire d’Excellence ( through the LabEx ParaFrap (grant number ANR-11-LABX-0024) (financial support for consumables and SA salary), the ParaMet PhD programme of Marie Curie Initial Training Network ( (FP7-PEOPLE-2011-ITN-290080) (financial support for consumables and MW salary) and the "Fondation pour le Recherche Médicale" (FRM, ("Equipe FRM", grant n°EQU201903007845) (financial support for consumables and EP salary). BR is supported by and the Institut Pasteur (financial support for consumables and salary of permanent positions). JCP's team from Metabolomics & Fluxomics facilities (Toulouse, France, is supported by the Agence National de Recherche (ANR, (grant MetaboHUB-ANR-11-INBS-0010) (financial support for consumables and salary of permanent positions).