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. Y. pseudotuberculosis causes severe infections in humans: Enteritis, Ileitis and Lymphadenitis, including several recent outbreaks of these diseases. In addition to its clinical relevance, the pathogen is important as an evolutionary ancestor of Y. pestis, the agent of plague. The German Research Foundation (DFG) supports the project through its priority program SPP1316 "Host Pathogen Interaction". We collaborate with the group of Petra Dersch from the Helmholtz-Centre for Infection Research (HZI).
- Combined analysis of metabolic fluxes and gene expression profiles of the Y. pseudotuberculosis wild type and defined virulence regulator mutants
- Identification of check points that link virulence and metabolism through integration of transcriptome and fluxome data
- Construction of mutants potentially affected in virulence control and testing of their infection potential in a mouse model
Bücker R, Heroven AK, Becker J, Dersch P, Wittmann C (2014) The pyruvate - tricarboxylic acid cycle node: a focal point of virulence control in the enteric pathogen Yersinia pseudotuberculosis. J. Biol. Chem. 289:30114-30132. Link.
Rücker N, Billig S, Bücker R, Jahn D, Wittmann C, Bange FC (2015) Acetate dissimilation and assimilation in Mycobacterium tuberculosis depend on carbon availability. J. Bacteriol. 197:3182-3190. Link.
Nuss, AM, Schuster, F, Roselius, L, Klein, J, Bücker, R, Herbst, K, Heroven, AK, Pisano, F, Wittmann, C, Münch, R, Müller, J, Jahn, D, Dersch, P (2016) A precise temperature-responsive bistable switch controlling Yersinia virulence. PLOS Pathogens. 12(12): e1006091. Link.