Staphylococcus aureus, one of most successful bacterial pathogens, can be found within the endothelium in infected animals and invades endothelial cells in culture. The effects of S. aureus on the endothelium are thought to cause symptoms of sepsis and prolonged survival of the bacteria within endothelial cells may underly chronic inflammation. Endothelial cell invasion is mediated by integrins and staphylococcal fibronectin binding proteins but the molecular events governing uptake are unknown. S. aureus can produce exotoxins which are unable to penetrate cell membranes, suggesting that these may be intracellularly produced. On this background we want to investigate the role of the cytoskeleton, both, during S. aureus uptake and as target of extracellularly and intracellularly secreted S. aureus virulence factors. One focus will be on the function of Rho GTP-binding proteins because these are crucial for bacterial uptake, intracellular transport and constitute substrates of an interesting S. aureus toxin, the epidermal cell differentiation inhibitor (EDIN).
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