Metabolism of intracellular Salmonella


Salmonella enterica is a facultative intracellular pathogen that efficiently proliferates within the 'Salmonella-containing vacuole' or SCV in various mammalian host cells. The composition of the SCV and avail¬ability of nutrients in the SCV is largely unknown. We aim to characterize the nutritional basis for intracellular replication of Salmonella on the cellular level. Two alternative models may explain the intracellular nutrition of Salmonella. Salmonella metabolism to available metabolites and molecules derived from the host cell. Alternatively, by means of translocated effector proteins Salmonella may direct vesicular traffic of the host cell in order to rapidly gain access to endocytosed material. This may allow intracellular Salmonella to metabolize nutrient of the external medium.
Using the isotopolog perturbation technique, we analyse the metabolic fluxes of substrates that can be utilized by Salmonella and the host cell or by Salmonella only.


We aim to

  • identify metabolic pathways of Salmonella defective in single or multiple pathways will be quantified
  • use reporter strains as sensors for the regulatory response of intracellular Salmonella
  • use experimental data to test and refine models based on bioinformatics analyses
  • investigate the changes in the metabolome of the mammalian host cells in response to Salmonella infection
  • use cell biology techniques such as live cell imaging to analyse the access of the SCV to the external environment as well as the redirection of host-derived vesicles for the nutrition of Salmonella

The multidisciplinary approaches and close collaborations with the platform techniques, we will provide a detailed view on the metabolism of Salmonella inside host cells. These data should be important for the definition of novel antimicrobial targets and strategies.


Funding

The project is currently funded by the DFG, project HE1964/14-1 within the priority program 1316 'Host-adapted metabolism of bacterial pathogens'


Collaborations

  • PD Dr. Wolfgang Eisenreich, TU München
  • Prof. Dr. Thomas Dandekar, Universität Würzburg
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