Glycerol suppresses glucose consumption in trypanosomes through metabolic contest.
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 met...
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2021
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oai:doaj.org-article:9f4cf4efa05d45079da2a16ebf1a090b2021-12-02T19:54:39ZGlycerol suppresses glucose consumption in trypanosomes through metabolic contest.1544-91731545-788510.1371/journal.pbio.3001359https://doaj.org/article/9f4cf4efa05d45079da2a16ebf1a090b2021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.3001359https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Microorganisms 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.Stefan AllmannMarion WargniesNicolas PlazollesEdern CahoreauMarc BiranPauline MorandErika PinedaHanna KulykCorinne AsencioOriana VillafrazLoïc RivièreEmmanuel TetaudBrice RotureauArnaud MourierJean-Charles PortaisFrédéric BringaudPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 19, Iss 8, p e3001359 (2021) |
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| collection |
DOAJ |
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| topic |
Biology (General) QH301-705.5 |
| spellingShingle |
Biology (General) QH301-705.5 Stefan Allmann Marion Wargnies Nicolas Plazolles Edern Cahoreau Marc Biran Pauline Morand Erika Pineda Hanna Kulyk Corinne Asencio Oriana Villafraz Loïc Rivière Emmanuel Tetaud Brice Rotureau Arnaud Mourier Jean-Charles Portais Frédéric Bringaud Glycerol suppresses glucose consumption in trypanosomes through metabolic contest. |
| description |
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. |
| format |
article |
| author |
Stefan Allmann Marion Wargnies Nicolas Plazolles Edern Cahoreau Marc Biran Pauline Morand Erika Pineda Hanna Kulyk Corinne Asencio Oriana Villafraz Loïc Rivière Emmanuel Tetaud Brice Rotureau Arnaud Mourier Jean-Charles Portais Frédéric Bringaud |
| author_facet |
Stefan Allmann Marion Wargnies Nicolas Plazolles Edern Cahoreau Marc Biran Pauline Morand Erika Pineda Hanna Kulyk Corinne Asencio Oriana Villafraz Loïc Rivière Emmanuel Tetaud Brice Rotureau Arnaud Mourier Jean-Charles Portais Frédéric Bringaud |
| author_sort |
Stefan Allmann |
| title |
Glycerol suppresses glucose consumption in trypanosomes through metabolic contest. |
| title_short |
Glycerol suppresses glucose consumption in trypanosomes through metabolic contest. |
| title_full |
Glycerol suppresses glucose consumption in trypanosomes through metabolic contest. |
| title_fullStr |
Glycerol suppresses glucose consumption in trypanosomes through metabolic contest. |
| title_full_unstemmed |
Glycerol suppresses glucose consumption in trypanosomes through metabolic contest. |
| title_sort |
glycerol suppresses glucose consumption in trypanosomes through metabolic contest. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/9f4cf4efa05d45079da2a16ebf1a090b |
| work_keys_str_mv |
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