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- W2002077151 abstract "Despite 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." @default.
- W2002077151 created "2016-06-24" @default.
- W2002077151 creator A5041672461 @default.
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- W2002077151 creator A5078759067 @default.
- W2002077151 creator A5084674318 @default.
- W2002077151 creator A5091002552 @default.
- W2002077151 date "2014-10-01" @default.
- W2002077151 modified "2023-10-03" @default.
- W2002077151 title "The Pyruvate-Tricarboxylic Acid Cycle Node" @default.
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- W2002077151 doi "https://doi.org/10.1074/jbc.m114.581348" @default.
- W2002077151 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4208018" @default.
- W2002077151 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25164818" @default.
- W2002077151 hasPublicationYear "2014" @default.
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