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Glycerol supports growth of the Trypanosoma brucei bloodstream forms in the absence of glucose: Analysis of metabolic adaptations on glycerol-rich conditions

dc.rights.licenseopenen_US
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorPINEDA, Erika
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorTHONNUS, Magali
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorMAZET, Muriel
dc.contributor.authorMOURIER, Arnaud
dc.contributor.authorCAHOREAU, Edern
dc.contributor.authorKULYK, Hanna
dc.contributor.authorDUPUY, Jean-William
dc.contributor.authorBIRAN, Marc
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorMASANTE, Cyril
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorALLMANN, Stefan
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorRIVIÈRE, Loïc
dc.contributor.authorROTUREAU, Brice
dc.contributor.authorPORTAIS, Jean-Charles
dc.contributor.authorBRINGAUD, Frédéric
dc.date.accessioned2023-06-21T13:48:28Z
dc.date.available2023-06-21T13:48:28Z
dc.date.issued2018-11-01
dc.identifier.issn1553-7366en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182747
dc.description.abstractEnThe bloodstream forms of Trypanosoma brucei (BSF), the parasite protist causing sleeping sickness, primarily proliferate in the blood of their mammalian hosts. The skin and adipose tissues were recently identified as additional major sites for parasite development. Glucose was the only carbon source known to be used by bloodstream trypanosomes to feed their central carbon metabolism, however, the metabolic behaviour of extravascular tissue-adapted parasites has not been addressed yet. Since the production of glycerol is an important primary function of adipocytes, we have adapted BSF trypanosomes to a glucose-depleted but glycerol-rich culture medium (CMM_Glyc/GlcNAc) and compared their metabolism and proteome to those of parasites grown in standard glucose-rich conditions (CMM_Glc). BSF were shown to consume 2-folds more oxygen per consumed carbon unit in CMM_Glyc/GlcNAc and were 11.5-times more sensitive to SHAM, a specific inhibitor of the plant-like alternative oxidase (TAO), which is the only mitochondrial terminal oxidase expressed in BSF. This is consistent with (i) the absolute requirement of the mitochondrial respiratory activity to convert glycerol into dihydroxyacetone phosphate, as deduced from the updated metabolic scheme and (ii) with the 1.8-fold increase of the TAO expression level compared to the presence of glucose. Proton NMR analysis of excreted end products from glycerol and glucose metabolism showed that these two carbon sources are metabolised through the same pathways, although the contributions of the acetate and succinate branches are more important in the presence of glycerol than glucose (10.2% versus 3.4% of the excreted end products, respectively). In addition, metabolomic analyses by mass spectrometry showed that, in the absence of glucose, 13C-labelled glycerol was incorporated into hexose phosphates through gluconeogenesis. As expected, RNAi-mediated down-regulation of glycerol kinase expression abolished glycerol metabolism and was lethal for BSF grown in CMM_Glyc/GlcNAc. Interestingly, BSF have adapted their metabolism to grow in CMM_Glyc/GlcNAc by concomitantly increasing their rate of glycerol consumption and decreasing that of glucose. However, the glycerol kinase activity was 7.8-fold lower in CMM_Glyc/GlcNAc, as confirmed by both western blotting and proteomic analyses. This suggests that the huge excess in glycerol kinase that is not absolutely required for glycerol metabolism, might be used for another yet undetermined non-essential function in glucose rich-conditions. Altogether, these data demonstrate that BSF trypanosomes are well-adapted to glycerol-rich conditions that could be encountered by the parasite in extravascular niches, such as the skin and adipose tissues.
dc.description.sponsorshipMetabolisme de l'acetyl-CoA et de l'acetate chez les trypanosomes: identification de nouvelles voies métaboliques spécifiques aux parasitesen_US
dc.description.sponsorshipVoies métaboliques glycosomales non glycolytiques: nouvelles fonctions pour le développement et la virulence des trypanosomesen_US
dc.description.sponsorshipAlliance française contre les maladies parasitaires - ANR-11-LABX-0024en_US
dc.language.isoENen_US
dc.rights.urihttp://creativecommons.org/licenses/by/
dc.subject.enGlucose metabolism
dc.subject.enTrypanosoma
dc.subject.enGlucose
dc.subject.enCell metabolism
dc.subject.enEnzyme metabolism
dc.subject.enOxygen metabolism
dc.subject.enPhosphates
dc.subject.enGlycerol
dc.title.enGlycerol supports growth of the Trypanosoma brucei bloodstream forms in the absence of glucose: Analysis of metabolic adaptations on glycerol-rich conditions
dc.typeArticle de revueen_US
dc.identifier.doi10.1371/journal.ppat.1007412en_US
dc.subject.halSciences du Vivant [q-bio]en_US
dc.subject.halSciences du Vivant [q-bio]/Microbiologie et Parasitologieen_US
dc.subject.halSciences du Vivant [q-bio]/Microbiologie et Parasitologie/Parasitologieen_US
dc.description.sponsorshipEuropeA systematic analysis of parasite metabolism - from metabolism to interventionen_US
bordeaux.journalPLoS Pathogensen_US
bordeaux.pagee1007412en_US
bordeaux.volume14en_US
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.issue11en_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierpasteur-01928252
hal.version1
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccCC BYen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=PLoS%20Pathogens&rft.date=2018-11-01&rft.volume=14&rft.issue=11&rft.spage=e1007412&rft.epage=e1007412&rft.eissn=1553-7366&rft.issn=1553-7366&rft.au=PINEDA,%20Erika&THONNUS,%20Magali&MAZET,%20Muriel&MOURIER,%20Arnaud&CAHOREAU,%20Edern&rft.genre=article


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