Cause and consequence: the contribution of the host´s microtubule cytoskeleton to Chlamydia pneumoniae infection

许多微生物病原体以宿主细胞骨架为靶标，促进感染过程。严格的细胞内革兰氏阴性细菌衣原体改变了真核细胞的细胞骨架，促进了入侵、复制和传播。肌动蛋白细胞骨架在衣原体感染过程中的作用已经得到了很好的证明，然而宿主S微管细胞骨架的影响还不是很清楚。在这个项目中，我们将确定微管细胞骨架在宿主细胞进入和人类肺炎衣原体发育周期中的作用。这种微生物沿着微管以一种未知的方式到达宿主S细胞的微管组织中心，到目前为止，只有一种肺炎衣原体蛋白CoPn被鉴定为体外微管调节剂。因此，我们将识别调节微管的衣原体效应蛋白，并确定这些蛋白在衣原体感染周期中的作用。由于肺炎链球菌不是遗传可及的，因此将在异源金黄色葡萄球菌裂解酵母系统中鉴定和鉴定微管调节蛋白。最后，我们将确定当宿主细胞的微管细胞骨架被肺炎链球菌破坏时对宿主细胞的影响。由于这种病原体的感染很常见，并与肺癌风险增加有关，我们将分析细菌感染是否干扰有丝分裂过程，从而导致非整倍体，这是癌症的标志之一。

Many microbial pathogens target the host cytoskeleton to promote the infection process. The strictly intracellular gram-negative bacterial pathogens Chlamydiae alter the eukaryotic cytoskeleton to facilitate invasion, replication and dissemination. The role of the actin cytoskeleton during the chlamydial course of infection has been well documented however the impact of the host´s microtubule cytoskeleton is less clear. In this project we will determine the role of the microtubule cytoskeleton during host cell entry and the developmental cycle of the human pathogen Chlamydia pneumoniae. This organism travels along microtubule tracks to the host´s cell microtubule organizing center in a non-defined manner and to date only a single C. pneumoniae protein, CopN, has been characterized as an in vitro microtubule modulator. Thus we will identify chlamydial effector proteins that modulate microtubules and determine the contribution of such proteins to the chlamydial infection cycle. As C. pneumoniae is not genetically accessible bacterial microtubule regulating proteins will be identified and characterized in the heterologous S. pombe fission yeast system. Lastly, we will determine the consequences for the host cell when its microtubule cytoskeleton is subverted by C. pneumoniae. As infection by this pathogen is common and has been associated with an increased risk for lung cancer we will analyze if bacterial infection interferes with mitotic processes and thus leads to aneuploidy, one of the hallmarks of cancer.