Extra- und intrazelluläre Funktionen von S. aureus Eap in der Wirtsabwehr

病原菌的组织渗透依赖于与宿主的细胞外基质和/或细胞表面或细胞相关黏附成分的相互作用。引起心内膜炎或不可愈合伤口的革兰氏阳性细菌进入血管包括与可溶性宿主成分的进一步相互作用，提供了一种整体防御逃避策略。在这里，金黄色葡萄球菌新的抗炎成分及其在宿主防御中的作用以及宿主清道夫分子在血管中用于细菌识别的概念将在体外和体内进行研究：(I)金黄色葡萄球菌释放某些与细菌黏附相关的细胞外黏附产物，但也是细菌保护，通过抑制宿主的S白细胞募集机制(先前的研究)来对抗炎症反应。EAP作用的潜在分子机制将在体外和体内模型中进行剖析和评估，并将考虑将EAP用作新的抗炎药物。(Ii)新的宿主EAP“受体”将通过使用噬菌体展示的单链抗体和蛋白质组分析的组合方法来鉴定。(Iii)将利用分子遗传学方法和血管疾病的动物模型研究内皮细胞“晚期糖基化终末产物受体”(RAGE)在识别(AGE)金黄色葡萄球菌、细菌侵入和炎症方面的作用，从而评估用于抗微生物治疗的新的抗粘连策略。

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.