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

金黄色葡萄球菌 Eap 在宿主防御中的胞外和胞内功能

• 批准号: 5390124
• 负责人: Professor Dr. Mathias Herrmann
• 金额: --
• 依托单位: Sektion Medizinische und Geographische Infektiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5390124?language=en
• 关键词: Extra; und; intrazellul; re; Funktionen

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.

致病菌的组织浸润取决于与宿主细胞外基质和/或细胞表面或细胞相关粘附成分的相互作用。引起心内膜炎或不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，提供整体防御逃避策略。本文将在体外和体内研究金黄色葡萄球菌的新抗炎成分及其在宿主防御中的作用，以及宿主清除分子在脉管系统中用于细菌识别的概念：(i)金黄色葡萄球菌释放某些与细菌粘附有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，也可以保护细菌免受炎症反应（先前的研究）。Eap功能的潜在分子机制将在体外和体内模型中进行解剖和评估；考虑将Eap作为新型抗炎药使用。（ii）新的宿主Eap“受体”将通过噬菌体单链抗体和蛋白质组分析相结合的方法进行鉴定。（iii）内皮细胞“晚期糖基化终产物受体”（RAGE）在识别（AGE-）S中的作用。利用分子遗传学方法和血管疾病动物模型研究金黄色葡萄球菌、细菌侵入和炎症，从而评估抗微生物治疗的新抗粘附策略。