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Procyclic trypanosomes recycle glucose catabolites and TCA cycle intermediates to stimulate growth in the presence of physiological amounts of proline

dc.rights.licenseopenen_US
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorVILLAFRAZ, Oriana
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorBIRAN, Marc
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorPINEDA, Erika
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorPLAZOLLES, Nicolas
dc.contributor.authorCAHOREAU, Edern
dc.contributor.authorORNITZ OLIVEIRA SOUZA, Rodolpho
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorTHONNUS, Magali
dc.contributor.authorALLMANN, Stefan
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorTETAUD, Emmanuel
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorRIVIÈRE, Loïc
dc.contributor.authorSILBER, Ariel
dc.contributor.authorBARRETT, Michael
dc.contributor.authorZÍKOVÁ, Alena
dc.contributor.authorBOSHART, Michael
dc.contributor.authorPORTAIS, Jean-Charles
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorBRINGAUD, Frédéric
dc.date.accessioned2023-05-24T14:19:45Z
dc.date.available2023-05-24T14:19:45Z
dc.date.issued2021
dc.identifier.issn1553-7366en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182326
dc.description.abstractEnTrypanosoma brucei, a protist responsible for human African trypanosomiasis (sleeping sickness), is transmitted by the tsetse fly where the procyclic forms of the parasite develop in the proline-rich (1–2 mM) and glucose-depleted digestive tract. Proline is essential for the midgut colonization of the parasite in the insect vector, however other carbon sources could be available and used to feed its central metabolism. Here we show that procyclic trypanosomes can consume and metabolize metabolic intermediates, including those excreted from glucose catabolism (succinate, alanine and pyruvate), with the exception of acetate, which is the ultimate end-product excreted by the parasite. Among the tested metabolites, tricarboxylic acid (TCA) cycle intermediates (succinate, malate and α-ketoglutarate) stimulated growth of the parasite in the presence of 2 mM proline. The pathways used for their metabolism were mapped by proton-NMR metabolic profiling and phenotypic analyses of thirteen RNAi and/or null mutants affecting central carbon metabolism. We showed that (i) malate is converted to succinate by both the reducing and oxidative branches of the TCA cycle, which demonstrates that procyclic trypanosomes can use the full TCA cycle, (ii) the enormous rate of α-ketoglutarate consumption (15-times higher than glucose) is possible thanks to the balanced production and consumption of NADH at the substrate level and (iii) α-ketoglutarate is toxic for trypanosomes if not appropriately metabolized as observed for an α-ketoglutarate dehydrogenase null mutant. In addition, epimastigotes produced from procyclics upon overexpression of RBP6 showed a growth defect in the presence of 2 mM proline, which is rescued by α-ketoglutarate, suggesting that physiological amounts of proline are not sufficient per se for the development of trypanosomes in the fly. In conclusion, these data show that trypanosomes can metabolize multiple metabolites, in addition to proline, which allows them to confront challenging environments in the fly.
dc.description.sponsorshipDéveloppement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovationen_US
dc.description.sponsorshipVoies métaboliques glycosomales non glycolytiques: nouvelles fonctions pour le développement et la virulence des trypanosomesen_US
dc.description.sponsorshipInteractions métaboliques entre les adipocytes et les trypanosomes, un nouveau paradigme pour les trypanosomoses - ANR-19-CE15-0004en_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.title.enProcyclic trypanosomes recycle glucose catabolites and TCA cycle intermediates to stimulate growth in the presence of physiological amounts of proline
dc.typeArticle de revueen_US
dc.identifier.doi10.1371/journal.ppat.1009204en_US
dc.subject.halSciences du Vivant [q-bio]/Microbiologie et Parasitologie/Parasitologieen_US
dc.subject.halSciences du Vivant [q-bio]/Microbiologie et Parasitologie/Protistologieen_US
bordeaux.journalPLoS Pathogensen_US
bordeaux.pagee1009204en_US
bordeaux.volume17en_US
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.issue3en_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierhal-03366686
hal.version1
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=PLoS%20Pathogens&rft.date=2021&rft.volume=17&rft.issue=3&rft.spage=e1009204&rft.epage=e1009204&rft.eissn=1553-7366&rft.issn=1553-7366&rft.au=VILLAFRAZ,%20Oriana&BIRAN,%20Marc&PINEDA,%20Erika&PLAZOLLES,%20Nicolas&CAHOREAU,%20Edern&rft.genre=article


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