Manipulating the actin cytoskeleton from the outside - induction of focal adhesion-like protein complexes an actin cytoskeletal rearrangements by fibbronectin-binding bacteria

大量的致病细菌和病毒利用宿主细胞整合素间接影响细胞肌动蛋白细胞骨架，从而获得进入宿主细胞的途径。金黄色葡萄球菌是医院获得性感染的主要原因，它利用纤维连接蛋白结合蛋白(FnBPs)触发肌动蛋白重排和被哺乳动物细胞摄取。在这里，我们将通过活细胞显微镜和质谱仪研究FnBP在感染细胞中诱导的焦点粘附样复合体的局部组装，招募的细胞质蛋白在肌动蛋白动力学中的作用，以及肌动蛋白细丝和肌动蛋白生成的力量在这些位置的细菌摄取中的联系。总之，这些研究旨在提供对整合素启动的内吞作用的全面了解，并测试这一新概念，即除了肌动蛋白聚合外，基于肌球蛋白的收缩是整合素介导的病原体内化的主要驱动力。

A large number of pathogenic bacteria and viruses exploit host cell integrins to indirectly influence the cellular actin cytoskeleton and to gain access to host cells. Staphylococcus atureus, a leading cause of hospital-acquired infections, utilizes fibronectin-binding proteins (FnBPs) to trigger actin rearrangements and uptake by mammalian cells. Here, we will investigate the FnBP-induced local assembly of focal-adhesion like complexes in the infected cells by live-cellmicroscopy and mass spectrometry, the role of recruited cytoplasmic proteins in actin dynamics as well as the connection between actin filaments and myo sin-generated forces in bacterial uptake at these sites. Together, these investigations are designed to provide a comprehensive understanding of integrin-initiated endocytosis and to test the novel concept that, in addition to actin polymerization, actin-myosin-based contraction is a major driving force behind integrinmediated internalization of pathogens.