Staphylococcus aureus infection of endothelial cells

金黄色葡萄球菌是引起血流感染的最常见原因之一。血管内金黄色葡萄球菌疾病，如心内膜炎和转移性感染的频繁诱导涉及粘附内皮细胞，诱导吞噬和细胞内持久性，然后是内皮细胞的激活和损伤。介导粘附和摄取以及调节内皮功能的因素仍然难以捉摸。纤维连接蛋白结合蛋白和纤维连接蛋白先前已被确定为与内皮细胞相互作用的关键决定因素。我们的数据现在揭示了一个同样重要的作用，苔壁酸，葡萄球菌细胞壁聚合物，作为粘附素结合到内皮细胞。脂壁酸也是内皮细胞细胞因子产生和表面蛋白上调的重要激活剂。我们想用我们的一组壁酸突变体和缺乏纤维连接蛋白结合蛋白的菌株来表征各种金黄色葡萄球菌因子对内皮细胞的结合、摄取和激活的贡献。Rho gtpase灭活金黄色葡萄球菌毒素EDIN与内皮功能的调节有关。虽然之前的实验是用纯化的EDIN进行的，但我们打算生成明确的金黄色葡萄球菌EDIN敲除和敲入突变体，并在细胞培养和动物实验中分析该毒素对内皮细胞活化的影响，以及金黄色葡萄球菌在内皮细胞内持续存在或损伤内皮细胞的能力。

Staphylococcus aureus is one of the most prevalent causes of blood stream infections. Endovascular S. aureus diseases such as endocarditis and the frequent induction of metastatic infections involve adherence to endothelial cells, induction of phagocytosis and intracellular persistence, followed by activation and damage of endothelial cells. The factors mediating adherence and uptake and modulating endothelial functions are still elusive. Fibronectin-binding proteins and fibronectin have previously been identified as crucial determinants for interactions with endothelial cells. Our data reveal now an equally important role of teichoic acids, staphylococcal cell wall polymers, as adhesins for binding to endothelial cells. Lipoteichoic acids are also important activators of cytokine production and surface protein upregulation in endothelial cells. We want to use our set of teichoic acids mutants and of strains deficient in fibronectin binding proteins to characterize the contribution of the various S. aureus factors to binding, uptake into, and activation of endothelial cells. The Rho GTPase-inactivating S. aureus toxin EDIN has been implicated in modulation of endothelial functions. While the previous experiments were carried out with purified EDIN, we intend to generate defined S. aureus EDIN knock-out and knock-in mutants and analyze the impact of this toxin on activation of endothelial cells and on the ability of S. aureus to persist within or damage endothelial cells in cell culture and animal experiments.