Establishment and maintenance of the chlamydial inclusion: requirement for septins and the inhibition of host cell translation

衣原体包涵体的建立和维持：对脓毒症的需求和宿主细胞翻译的抑制

• 批准号: 198125886
• 负责人: Professor Dr. Georg Häcker
• 金额: --
• 依托单位: Department für Medizinische Mikrobiologie, Virologie und Hygiene
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/198125886?language=en
• 关键词: Establishment; maintenance; chlamydial; inclusion; requirement

Chlamydia trachomatis, a frequent agent of human eye infection and sexually transmitted disease, is an obligate intracellular bacterium that grows in a membrane-bounded vacuole (the inclusion) in the cytoplasm of the human host cell. Unlike other pathogen-containing vacuoles, the Chlamydia-inclusion lacks markers of endocytic transport but acquires components from the post-Golgi exocytic vesicular pathway. Chlamydia induces fragmentation of the Golgi apparatus through cleavage of the Golgi-matrix protein golgin-84, and this has been linked to lipid acquisition by the inclusion. We have recently shown that the Chlamydia protease CPAF cleaves golgin-84 and that ectopically expressed CPAF is sufficient to induce Golgi-fragmentation. Further, the synthetic caspase-1-inhibitor WEHDfmk was identified as an inhibitor of CPAF. In this project we aim at understanding mechanism and importance of this function of CPAF. CPAF will be either specifically inhibited during infection or ectopically expressed. The effect of these experimental manipulations on vesicular transport, transport to the inclusion and the development of inclusion and bacteria will be monitored using cell biological as well as proteomic and lipidomic approaches. The evolutionary conservation of this mechanism will further be tested by the analysis of CPAF from species of Chlamydia-like organisms. These studies will enhance our understanding of maintenance and development of the chlamydial inclusion and the mechanisms and importance of the hijacking of the post-Golgi exocytic pathway by an intracellular pathogen.

沙眼衣原体（Chlamydia trachomatis）是一种专性细胞内细菌，在人类宿主细胞的细胞质中生长于有膜的空泡（内含物）中，是人类眼部感染和性传播疾病的常见病原体。与其他病原体含有空泡，衣原体包涵体缺乏内吞运输的标志物，但收购组件后高尔基体胞吐囊泡途径。衣原体通过切割高尔基体基质蛋白golgin-84诱导高尔基体的片段化，并且这已经与通过内含物获得脂质相关联。我们最近表明，衣原体蛋白酶CPAF切割高尔基体-84和异位表达的CPAF足以诱导高尔基体片段化。此外，合成的半胱天冬酶-1-抑制剂WEHDfectin被鉴定为CPAF的抑制剂。在这个项目中，我们的目的是了解机制和重要性，这一职能的CPAF。CPAF在感染过程中被特异性抑制或异位表达。将使用细胞生物学以及蛋白质组学和脂质组学方法监测这些实验操作对囊泡转运、转运至包涵体以及包涵体和细菌的发育的影响。这种机制的进化保守性将进一步测试的CPAF从衣原体样生物物种的分析。这些研究将增强我们对衣原体包涵体的维持和发展以及细胞内病原体劫持高尔基体后胞外途径的机制和重要性的理解。