Staphylococcus aureus infection of endothelial cells

金黄色葡萄球菌感染内皮细胞

• 批准号: 5389431
• 负责人: Professor Dr. Andreas Peschel
• 金额: --
• 依托单位: Institut für Medizinische Mikrobiologie und Hygiene
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5389431?language=en
• 关键词: Staphylococcus; aureus; infection; endothelial; cells

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.

金黄色葡萄球菌是血流感染的最常见原因之一。血管内S.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对内皮细胞的粘附、吞噬作用的诱导和细胞内持久性，随后是内皮细胞的活化和损伤。介导粘附和摄取以及调节内皮功能的因子仍然是难以捉摸的。纤连蛋白结合蛋白和纤连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。我们的数据显示，现在同样重要的作用磷壁酸，葡萄球菌细胞壁聚合物，作为粘附素结合内皮细胞。脂磷壁酸也是内皮细胞中细胞因子产生和表面蛋白上调的重要激活剂。我们想用我们的磷壁酸突变体和纤连蛋白结合蛋白缺乏的菌株来表征各种S。金黄色葡萄球菌因子与内皮细胞的结合、摄取和活化。Rho GTP酶失活S.金黄色葡萄球菌毒素EDIN与内皮功能的调节有关。虽然以前的实验是用纯化的EDIN进行的，但我们打算产生定义的S。金黄色葡萄球菌EDIN敲除和敲入突变体，并分析该毒素对内皮细胞活化和对S.在细胞培养和动物实验中，金黄色葡萄球菌在内皮细胞内持续存在或损伤内皮细胞。