Kumar Yadunanda, Valdivia Raphael H
Department of Molecular Genetics and Microbiology and Center for Microbial Pathogenesis, Duke University Medical Center, Durham, NC 27710, USA.
Cell Host Microbe. 2008 Aug 14;4(2):159-69. doi: 10.1016/j.chom.2008.05.018.
The obligate intracellular bacterial pathogen Chlamydia trachomatis replicates within a large vacuole or "inclusion" that expands as bacteria multiply but is maintained as an intact organelle. Here, we report that the inclusion is encased in a scaffold of host cytoskeletal structures made up of a network of F-actin and intermediate filaments (IF) that act cooperatively to stabilize the pathogen-containing vacuole. Formation of F-actin at the inclusion was dependent on RhoA, and its disruption led to the disassembly of IFs, loss of inclusion integrity, and leakage of inclusion contents into the host cytoplasm. In addition, IF proteins were processed by the secreted chlamydial protease CPAF to form filamentous structures at the inclusion surface with altered structural properties. We propose that Chlamydia has co-opted the function of F-actin and IFs to stabilize the inclusion with a dynamic, structural scaffold while minimizing the exposure of inclusion contents to cytoplasmic innate immune-surveillance pathways.
专性胞内细菌病原体沙眼衣原体在一个大液泡或“包涵体”内复制,该包涵体随着细菌繁殖而扩大,但作为一个完整的细胞器得以维持。在此,我们报告称,包涵体被宿主细胞骨架结构的支架所包裹,该支架由F-肌动蛋白和中间丝(IF)网络组成,它们协同作用以稳定含病原体的液泡。包涵体处F-肌动蛋白的形成依赖于RhoA,其破坏导致中间丝解体、包涵体完整性丧失以及包涵体内容物泄漏到宿主细胞质中。此外,IF蛋白被分泌的衣原体蛋白酶CPAF加工,以在包涵体表面形成具有改变的结构特性的丝状结构。我们提出,衣原体利用F-肌动蛋白和中间丝的功能,通过动态的结构支架来稳定包涵体,同时尽量减少包涵体内容物暴露于细胞质先天性免疫监测途径。