The role of endothelial cell receptors and bacterial products in Staphylococcus aureus endovascular infection and novel strategies for anti-inflammatory interventions

病原菌的组织浸润取决于与宿主的细胞外基质和/或细胞表面或细胞相关粘附组分的相互作用。引起心内膜炎或不愈合伤口的革兰氏阳性菌的血管进入包括与可溶性宿主组分的进一步相互作用，从而提供总体防御逃避策略。在这里，新的抗炎成分的S。金黄色葡萄球菌及其在宿主防御中的作用以及用于细菌识别的脉管系统中的宿主清除分子的概念将在体外和体内进行研究：金黄色葡萄球菌释放某些与细菌粘附相关的细胞外粘附产物（Eap），但由于抑制宿主的白细胞募集机制（先前的研究），也可保护细菌对抗炎症反应。Eap功能的潜在分子机制将在体外和体内模型中进行分析和评估;将考虑使用Eap作为新的抗炎药物。ii）新的宿主Eap“受体”将通过使用噬菌体展示单链抗体和蛋白质组分析的组合方法来鉴定。iii）内皮细胞“晚期糖基化终产物受体”（receptor for advanced glycation endproducts，AGE-）在识别（AGE-）S中的作用。将利用分子遗传学方法和血管疾病的动物模型来研究金黄色葡萄球菌、细菌进入和炎症，从而能够评估用于抗微生物治疗的新的抗粘附策略。

Tissue infiltration by pathogenic bacteria depends on interactions with the extracellular matrix and/or cell suface or cell-associated adhesive components of the host. Vascular entry of Gram-positive bacteria causing endocarditis or non-healing wounds includes further interactions with soluble host components providing an overall defense evasion strategy. Here, new anti-inflammatory components of S. aureus and their role in host defense as well as the concept of host scavenger molecules in the vasculature for bacterial recognition will be studied in vitro and in vivo: i) S. aureus releases certain extracellular adhesion products (Eap), relevant for bacterial adherence, but also being bacteria-pro-tective against the inflammatory response due to inhibition of the host´s leukocyte recruitment machinery (previous studies). The underlying molecular mechanisms of Eap functions will be dis-sected and evaluated in in vitro and in vivo models; the use of Eap as new anti-inflammatory drug will be considered. ii) Novel host Eap "receptors" will be identified by a combined approach using phage displayed single-chain antibodies and proteome analysis. iii) The contribution of the endothelial cell "receptor for advanced glycation endproducts" (RAGE) in recognition of (AGE-)S. aureus, bacterial entry and inflammation will be studied utilizing molecular genetic approaches and animal models of vascular diseases, allowing to evaluate new anti-adhesion strategies for anti-microbial therapy.