ABSTRACT

To evaluate potential pathomechanisms in the induction of infective endocarditis (IE), 34 Staphylococcus aureus (S. aureus) isolates, collected from patients with S. aureus endocarditis and from healthy individuals were investigated both in vitro and in vivo. S. aureus isolates were tested in vitro for their cytotoxicity, invasion and the association with platelets. Virulence factor expression profiles and cellular response were additionally investigated and tested for correlation with the ability of S. aureus to induce vegetations on the aortic valves in vivo. In an animal model of IE valvular conspicuity was assessed by in vivo magnetic resonance imaging at 9.4 T, histology and enrichment gene expression analysis. All S. aureus isolates tested in vivo caused a reliable infection and inflammation of the aortic valves, but could not be differentiated and categorized according to the measured in vitro virulence profiles and cytotoxicity. Results from in vitro assays did not correlate with the severity of IE. However, the isolates differed substantially in the activation and inhibition of pathways connected to the extracellular matrix and inflammatory response. Thus, comprehensive approaches of host-pathogen interactions and corresponding immune pathways are needed for the evaluation of the pathogenic capacity of bacteria. An improved understanding of the interaction between virulence factors and immune response in S. aureus infective endocarditis would offer novel possibilities for the development of therapeutic strategies and specific diagnostic imaging markers.

摘要

为了评估诱导感染性心内膜炎 (IE) 的潜在病理机制，在体外和体内研究了从金黄色葡萄球菌心内膜炎患者和健康个体中收集的 34 株金黄色葡萄球菌( S. aureus ) 分离株。在体外测试金黄色葡萄球菌分离株的细胞毒性、侵袭性和与血小板的关联。另外研究并测试了毒力因子表达谱和细胞反应与金黄色葡萄球菌在体内诱导主动脉瓣上的植被的能力的相关性。在 IE 瓣膜显着性的动物模型中，通过以下方法评估9.4 T的体内磁共振成像，组织学和富集基因表达分析。在体内测试的所有金黄色葡萄球菌分离株都引起了可靠的主动脉瓣感染和炎症，但无法根据测量的体外毒力谱和细胞毒性进行区分和分类。体外结果检测与 IE 的严重程度无关。然而，分离物在与细胞外基质和炎症反应相关的途径的激活和抑制方面存在显着差异。因此，需要宿主-病原体相互作用和相应免疫途径的综合方法来评估细菌的致病能力。更好地理解金黄色葡萄球菌感染性心内膜炎的毒力因子和免疫反应之间的相互作用，将为开发治疗策略和特异性诊断成像标志物提供新的可能性。