Metabolism of intracellular Salmonella enterica: One liefstyle in intracellular infections

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The successful intracellular lifestyle of Salmonella enterica relies on the adaptation to nutritional conditions within the Salmonella-containing vacuole (SCV) in host cells. Based on previous results, metabolic requirements for Salmonella in the SCV shall be characterized further. This includes (i) prediction of intracellular phenotypes of mutant strains based on elementary mode modeling and experimental tests, (ii) isotopolog profiling using 13C compounds in intracellular Salmonella, and (iii) complementation of metabolic defects for attenuated mutant strains. The collaborative work between the Dandekar and Hensel groups proposed for the second funding period should lead to a comprehen-sive understanding of the metabolic requirements of the intracellular lifestyle of Salmonella. Further analyses of intracellular phenotypes will be based on improved elementary modes predictions. Vice versa, based on analyses of mutant phenotypes and isotopolog analyses, iterative refinement of metabolic flux models will be achieved. An ultimate goal will be the comprehensive understanding of the adaptation of Salmonella to the life in a membrane-bound compartment in mammalian cells. Towards an integrated model, comparison of the Salmonella lifestyle with other pathogens and their metabolic requirements during infection, in particular cytoplasmic as for Listeria, or membrane-bound as for Legionella will be made in the context of the priority program.