Mechanisms of cell death induction by Staphylococcus aureus in leucocytes and endothelial cells

金黄色葡萄球菌诱导白细胞和内皮细胞死亡的机制

• 批准号: 137502261
• 负责人: Professorin Dr. Bettina Löffler
• 金额: --
• 依托单位: Institut für Medizinische Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/137502261?language=en
• 关键词: Mechanisms; cell; death; induction; Staphylococcus

Staphylococcus aureus is a frequent human pathogen, which can induce a multitude of serious diseases, such as endocarditis, pneumonia, soft-tissue infections and septic shock. The course of infection is determined by various staphylococcal virulence factors, including the release of toxins, bacterial adhesion and host cell invasion. Only recently, different research groups, which applied murine disease models, have published conflicting results concerning the role of the S. aureus pore-forming toxins α-hemolysin (α-toxin) and Panton-Valentine leukocidin (PVL). Both toxins have been associated with severe necrotizing infections. They exhibit cytolytic effects, which are restricted to certain cell types; however, their mechanisms of action are largely unknown. This project is designed to investigate the impact of defined S. aureus virulence factors, with special regard to α-toxin and PVL, on human leucocytes and endothelial cells, which come into close contact to bacteria during endo- and perivascular infections. On the staphylococcal side additional factors will be explored, which act together with α-toxin and PVL and contribute to the infection process. On the host cell side receptors and signal transduction pathways will be analyzed, which are activated during the infection process and induce cell death. Detailed knowledge about the cytolytic activity of S. aureus provides new rationale for therapeutic intervention in severe S. aureus infections.

金黄色葡萄球菌是人类常见的致病菌，可引起心内膜炎、肺炎、软组织感染和感染性休克等多种严重疾病。葡萄球菌的感染过程由多种毒力因素决定，包括毒素的释放、细菌的黏附和宿主细胞的入侵。直到最近，不同的研究小组应用小鼠疾病模型，发表了关于金黄色葡萄球菌毛孔形成毒素α-溶血素(α-毒素)和潘顿-瓦伦丁杀白素(PVL)的作用的相互矛盾的结果。这两种毒素都与严重的坏死性感染有关。它们表现出仅限于某些细胞类型的细胞溶解作用；然而，它们的作用机制在很大程度上是未知的。本项目旨在研究明确的金黄色葡萄球菌毒力因子，特别是α毒素和PVL，对人白细胞和内皮细胞的影响，这些细胞在血管内和血管周围感染期间与细菌密切接触。在葡萄球菌方面，将探索其他因素，这些因素与α毒素和PVL共同作用，促进感染过程。在宿主细胞方面，将分析在感染过程中被激活并诱导细胞死亡的受体和信号转导途径。对金黄色葡萄球菌溶细胞活性的详细了解为治疗严重的金黄色葡萄球菌感染提供了新的理论基础。