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Gluconeogenesis is essential for trypanosome development in the tsetse fly vector

dc.rights.licenseopenen_US
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorWARGNIES, Marion
dc.contributor.authorBERTIAUX, Eloise
dc.contributor.authorCAHOREAU, Edern
dc.contributor.authorZIEBART, Nicole
dc.contributor.authorCROUZOLS, Aline
dc.contributor.authorMORAND, Pauline
dc.contributor.authorBIRAN, Marc
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorALLMANN, Stefan
dc.contributor.authorHUBERT, Jane
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorVILLAFRAZ, Oriana
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorMILLERIOUX, Yoann
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorPLAZOLLES, Nicolas
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorASENCIO, Corinne
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorRIVIÈRE, Loïc
dc.contributor.authorROTUREAU, Brice
dc.contributor.authorBOSHART, Michael
dc.contributor.authorPORTAIS, Jean-Charles
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorBRINGAUD, Frédéric
dc.date.accessioned2023-06-21T13:14:51Z
dc.date.available2023-06-21T13:14:51Z
dc.date.issued2018-12-17
dc.identifier.issn1553-7366en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182742
dc.description.abstractEnIn the glucose-free environment that is the midgut of the tsetse fly vector, the procyclic form of Trypanosoma brucei primarily uses proline to feed its central carbon and energy metabolism. In these conditions, the parasite needs to produce glucose 6-phosphate (G6P) through gluconeogenesis from metabolism of non-glycolytic carbon source(s). We showed here that two phosphoenolpyruvate-producing enzymes, PEP carboxykinase (PEPCK) and pyruvate phosphate dikinase (PPDK) have a redundant function for the essential gluconeogenesis from proline. Indeed, incorporation of 13C-enriched proline into G6P was abolished in the PEPCK/PPDK null double mutant (Δppdk/Δpepck), but not in the single Δppdk and Δpepck mutant cell lines. The procyclic trypanosome also uses the glycerol conversion pathway to feed gluconeogenesis, since the death of the Δppdk/Δpepck double null mutant in glucose-free conditions is only observed after RNAi-mediated down-regulation of the expression of the glycerol kinase, the first enzyme of the glycerol conversion pathways. Deletion of the gene encoding fructose-1,6-bisphosphatase (Δfbpase), a key gluconeogenic enzyme irreversibly producing fructose 6-phosphate from fructose 1,6-bisphosphate, considerably reduced, but not abolished, incorporation of 13C-enriched proline into G6P. In addition, the Δfbpase cell line is viable in glucose-free conditions, suggesting that an alternative pathway can be used for G6P production in vitro. However, FBPase is essential in vivo, as shown by the incapacity of the Δfbpase null mutant to colonise the fly vector salivary glands, while the parental phenotype is restored in the Δfbpase rescued cell line re-expressing FBPase. The essential role of FBPase for the development of T. brucei in the tsetse was confirmed by taking advantage of an in vitro differentiation assay based on the RNA-binding protein 6 over-expression, in which the procyclic forms differentiate into epimastigote forms but not into mammalian-infective metacyclic parasites. In total, morphology, immunofluorescence and cytometry analyses showed that the differentiation of the epimastigote stages into the metacyclic forms is abolished in the Δfbpase mutant.
dc.description.sponsorshipVoies métaboliques glycosomales non glycolytiques: nouvelles fonctions pour le développement et la virulence des trypanosomesen_US
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.sponsorshipAlliance française contre les maladies parasitairesen_US
dc.language.isoENen_US
dc.rights.urihttp://creativecommons.org/licenses/by/
dc.title.enGluconeogenesis is essential for trypanosome development in the tsetse fly vector
dc.typeArticle de revueen_US
dc.identifier.doi10.1371/journal.ppat.1007502en_US
dc.subject.halSciences du Vivant [q-bio]/Microbiologie et Parasitologieen_US
dc.subject.halSciences du Vivant [q-bio]/Microbiologie et Parasitologie/Parasitologieen_US
bordeaux.journalPLoS Pathogensen_US
bordeaux.pagee1007502en_US
bordeaux.volume14en_US
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.issue12en_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierpasteur-01963538
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=2018-12-17&rft.volume=14&rft.issue=12&rft.spage=e1007502&rft.epage=e1007502&rft.eissn=1553-7366&rft.issn=1553-7366&rft.au=WARGNIES,%20Marion&BERTIAUX,%20Eloise&CAHOREAU,%20Edern&ZIEBART,%20Nicole&CROUZOLS,%20Aline&rft.genre=article


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