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General background

The central question of research of our group is the understanding of host-pathogen interactions on the molecular level. For a complete understanding of this critical interface, we need to integrate the immune defence of the host, the response of the pathogen, the function and regulation of virulence determinants and ultimately, the manipulation of host cell function by virulence factors of pathogens.
Our group uses Salmonella enterica as a model organism for the study of host-pathogen interaction. Infections with S. enterica are frequent and of high clinical importance. In Germany, Salmonella is the most frequent bacterial agent of gastrointestinal infections and worldwide typhoid fever is a major health problem. While typhoid fever is very rare in Germany, there is an increasing number of cases of non-typhoidal systemic infections, especially in very young or elderly individuals. The treatment of these infections is complicated by the frequent multi-resistance against antibiotics. A number of S. enterica infections also develops into persistent diseases which are associated with shedding of the bacteria.

In addition to the importance as a frequent pathogen, S. enterica is a very useful model organism for the study of the molecular mechanisms of host pathogen interaction. Salmonella can be easily genetically modified and a vast body of data on genome sequences and gene regulation is available. There are also well established cell culture and animal models of infection that simulate human systemic infection, localized gastroenteritis, as well as bacterial persistence.

We have recently discovered novel mechanisms of the modification of host cell transport processes by intracellular Salmonella. In particular, the organization of the microtubule cytoskeleton and the vesicular transport along microtubules are modified by activities of the pathogen. This activity might be the molecular basis of various previously described phenotypes, such as the biogenesis of a unique parasitophorous vacuole, defence of the pathogen against innate immune functions, the inhibition of antigen presentation by dendritic cells, or the altered exocytosis in infected cells.

A long term goal is the transfer the know-how from the Salmonella model to other important pathogens that are more difficult to study. One pathogen of interest is Chlamydia spp., which is of high clinical relevance and shows some interesting similarities to Salmonella pathogenesis. Furthermore, the detailed understanding of bacterial virulence factors may allow to device new vaccination strategies as well as novel form of anti-microbial therapy.

Image "Replication.gif"
Intracellular replication of S. enterica in the murine macrophage-like cell line RAW 264.7. Salmonella express green fluorescent protein (GFP, green). The macrophage cytoskeleton is stained with phalloidin-TexasRed (red).
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