Modeling metabolism in intracellular infections comparing Salmonella and Listeria

• Applicant: Professor Dr. Thomas Dandekar
• Subject Area: Bioinformatics and Theoretical Biology
• Term: from 2008 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 71820928

We want to model metabolism in intracellular infections. We will compare an intra-vacuolar strategy (Salmonella, Salmonella enterica serovar Typhimurium (S. Typhimurium) Gram negative) with a cytoplasmic strategy (Listeria, L. monocytogenes, Gram positive) and examine subsequently whether the results found can be generalized to other bacteria and their infection strategy. During infection, the metabolism of these organisms is intricately interacting and intertwined with the metabolism of the host. Only by this bacterial growth and further infection is possible. The description of metabolism in this situation allows furthermore to identify potential target proteins for antibiotic strategies and where a disturbance of the delicate metabolic interaction of host and parasite could modify or stop the infectious process (intensive collaboration with the bioanalytical platform, in particular PD Eisenreich, and with Prof. Hensel and Bumann (Salmonella), Prof. Fuchs (Listeria); further collaborations with Dr. Heuner (Legionella), Dr. Rudel (Chlamydia) and others). Furthermore, we want to understand the pathophysiology of the infection process, resulting amino acid fluxes, the utilization of different carbohydrate sources as well as metabolic bottle necks. Intervention strategies will be clarified as well as the effect of pathological factors, for instance infection specific transcription factors. In an iterative process new predictions will lead to new experiments and these to further improved models. The application of bioinformatics to these questions allows furthermore the development of new methods and improved predictions (including algorithms for improved modeling of (i) metabolism, (ii) metabolic networks and (iii) regulation of intracellular infection). All these techniques, software and results will be available for the whole SPP.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1316: Host-adapted Metabolism of Bacterial Pathogens