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

因果关系：宿主微管细胞骨架对肺炎衣原体感染的贡献

基本信息

批准号：
275334639
负责人：
Professorin Dr. Ursula-Nicole Fleig
金额：
--
依托单位：
Institut für Funktionelle Genomforschung der Mikroorganismen
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2015
资助国家：
德国
起止时间：
2014-12-31 至 2018-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/275334639?language=en
关键词：
Cause consequence contribution host microtubule

项目摘要

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.

许多微生物病原体靶向宿主细胞骨架以促进感染过程。严格的细胞内革兰氏阴性细菌病原体衣原体改变真核细胞骨架以促进侵袭、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得到充分证明。然而，宿主微管细胞骨架的影响还不太清楚，在这个项目中，我们将确定微管细胞骨架在宿主过程中的作用。人类病原体肺炎衣原体的细胞进入和发育周期。这种生物体以一种不确定的方式沿着微管轨道移动到宿主的细胞微管组织中心，迄今为止，仅对一种肺炎衣原体蛋白 CopN 进行了表征。因此，我们将鉴定调节微管的衣原体效应蛋白，并确定此类蛋白对衣原体感染周期的贡献，因为肺炎衣原体无法通过遗传途径获得。最后，我们将确定当宿主细胞的微管细胞骨架被肺炎衣原体破坏时对宿主细胞的影响，因为这种病原体的感染很常见并且已经发生。由于细菌感染与肺癌风险增加有关，我们将分析细菌感染是否会干扰有丝分裂过程，从而导致非整倍体（癌症的标志之一）。