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dc.contributor.authorBücker, René
dc.contributor.authorHeroven, Ann Kathrin
dc.contributor.authorBecker, Judith
dc.contributor.authorDersch, Petra
dc.contributor.authorWittmann, Christoph
dc.date.accessioned2015-02-25T13:36:45Zen
dc.date.available2015-02-25T13:36:45Zen
dc.date.issued2014-10-24en
dc.identifier.citationThe pyruvate-tricarboxylic acid cycle node: a focal point of virulence control in the enteric pathogen Yersinia pseudotuberculosis. 2014, 289 (43):30114-32 J. Biol. Chem.en
dc.identifier.issn1083-351Xen
dc.identifier.pmid25164818en
dc.identifier.doi10.1074/jbc.M114.581348en
dc.identifier.urihttp://hdl.handle.net/10033/345304en
dc.description.abstractDespite our increasing knowledge of the specific pathogenicity factors in bacteria, the contribution of metabolic processes to virulence is largely unknown. Here, we elucidate a tight connection between pathogenicity and core metabolism in the enteric pathogen Yersinia pseudotuberculosis by integrated transcriptome and [(13)C]fluxome analysis of the wild type and virulence-regulator mutants. During aerobic growth on glucose, Y. pseudotuberculosis reveals an unusual flux distribution with a high level of secreted pyruvate. The absence of the transcriptional and post-transcriptional regulators RovA, CsrA, and Crp strongly perturbs the fluxes of carbon core metabolism at the level of pyruvate metabolism and the tricarboxylic acid (TCA) cycle, and these perturbations are accompanied by transcriptional changes in the corresponding enzymes. Knock-outs of regulators of this metabolic branch point and of its central enzyme, pyruvate kinase (ΔpykF), result in mutants with significantly reduced virulence in an oral mouse infection model. In summary, our work identifies the pyruvate-TCA cycle node as a focal point for controlling the host colonization and virulence of Yersinia.
dc.language.isoenen
dc.subject.meshAdaptation, Physiologicalen
dc.subject.meshAnimalsen
dc.subject.meshBacterial Proteinsen
dc.subject.meshBiomassen
dc.subject.meshCitric Acid Cycleen
dc.subject.meshEscherichia colien
dc.subject.meshFemaleen
dc.subject.meshGene Expression Regulation, Bacterialen
dc.subject.meshGene Regulatory Networksen
dc.subject.meshGlucoseen
dc.subject.meshIronen
dc.subject.meshMetabolic Flux Analysisen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred BALB Cen
dc.subject.meshMolecular Weighten
dc.subject.meshMutationen
dc.subject.meshPyruvatesen
dc.subject.meshStress, Physiologicalen
dc.subject.meshTranscriptomeen
dc.subject.meshVirulenceen
dc.subject.meshYersinia pseudotuberculosisen
dc.subject.meshYersinia pseudotuberculosis Infectionsen
dc.titleThe pyruvate-tricarboxylic acid cycle node: a focal point of virulence control in the enteric pathogen Yersinia pseudotuberculosis.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalThe Journal of biological chemistryen
refterms.dateFOA2018-06-13T00:28:17Z
html.description.abstractDespite our increasing knowledge of the specific pathogenicity factors in bacteria, the contribution of metabolic processes to virulence is largely unknown. Here, we elucidate a tight connection between pathogenicity and core metabolism in the enteric pathogen Yersinia pseudotuberculosis by integrated transcriptome and [(13)C]fluxome analysis of the wild type and virulence-regulator mutants. During aerobic growth on glucose, Y. pseudotuberculosis reveals an unusual flux distribution with a high level of secreted pyruvate. The absence of the transcriptional and post-transcriptional regulators RovA, CsrA, and Crp strongly perturbs the fluxes of carbon core metabolism at the level of pyruvate metabolism and the tricarboxylic acid (TCA) cycle, and these perturbations are accompanied by transcriptional changes in the corresponding enzymes. Knock-outs of regulators of this metabolic branch point and of its central enzyme, pyruvate kinase (ΔpykF), result in mutants with significantly reduced virulence in an oral mouse infection model. In summary, our work identifies the pyruvate-TCA cycle node as a focal point for controlling the host colonization and virulence of Yersinia.


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