Rolle des Zytoskeletts bei der Endothel-Infektion durch S. aureus

金黄色葡萄球菌是最成功的细菌病原体之一，可以在感染动物的内皮中发现并侵入培养的内皮细胞。金黄色葡萄球菌对内皮细胞的影响被认为会引起脓毒症的症状，内皮细胞内细菌的长期存活可能是慢性炎症的基础。内皮细胞侵袭是由整合素和葡萄球菌纤维连接蛋白结合蛋白介导的，但控制摄取的分子事件尚不清楚。金黄色葡萄球菌可以产生不能穿透细胞膜的外毒素，这表明这些毒素可能是在细胞内产生的。在此背景下，我们希望研究细胞骨架在金黄色葡萄球菌摄取过程中的作用，以及作为细胞外和细胞内分泌的金黄色葡萄球菌毒力因子的目标。其中一个重点将放在Rho gtp结合蛋白的功能上，因为这些蛋白对细菌摄取、细胞内运输至关重要，并且构成了一种有趣的金黄色葡萄球菌毒素——表皮细胞分化抑制剂（EDIN）的底物。

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).