The Pyruvate – Tricarboxylic Acid Cycle Node: a Focal Point of Virulence Control in the Enteric Pathogen Yersinia pseudotuberculosis [Metabolism]
August 27th, 2014 by Bucker, R., Heroven, A. K., Becker, J., Dersch, P., Wittmann, C.
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 13C-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 particularly 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 colonisation and virulence of Yersinia.