Chlamydia trachomatis CT229 Subverts Rab GTPase-Dependent CCV Trafficking Pathways to Promote Chlamydial Infection
Chlamydia trachomatis CT229 Subverts Rab GTPase-Dependent CCV Trafficking Pathways to Promote Chlamydial Infection
复制标题
DOI：
10.1016/j.celrep.2019.02.079
复制
发表时间：
2019-03-19
期刊：
影响因子：
8.8
通讯作者：
Weber, Mary M.
中科院分区：
文献类型：
--
作者：
Faris, Robert;Merling, Marlena;Weber, Mary M.
衣原体感染需要形成一个膜结合的空泡，称为包涵体，它与选定的宿主细胞器进行广泛的相互作用。最近的研究表明，INC蛋白CT229在衣原体包涵体的形成和维持中的重要性得到了强调，研究表明，感染过程中没有它会导致细菌复制减少、包涵体过早溶解和宿主细胞死亡。以前的报道表明，CT229与Rab GTP酶结合；然而，这种相互作用的生理意义尚不清楚。在这里，我们表明，CT229通过招募多个Rab GTP酶及其同源效应物来调节宿主的多囊泡运输。我们证明，CT229特异性地调控包被蛋白的囊泡转运，并调节转铁蛋白和甘露糖-6-磷酸受体的转运，这两种受体对衣原体的正常发育都是至关重要的。这项研究强调，CT229是衣原体感染所必需的多个宿主囊泡运输途径的主要调节者。
Chlamydial infection requires the formation of a membrane-bound vacuole, termed the inclusion, that undergoes extensive interactions with select host organelles. The importance of the Inc protein CT229 in the formation and maintenance of the chlamydial inclusion was recently highlighted by studies demonstrating that its absence during infection results in reduced bacterial replication, premature inclusion lysis, and host cell death. Previous reports have indicated that CT229 binds Rab GTPases; however, the physiological implications of this interaction are unknown. Here, we show that CT229 regulates host multivesicular trafficking by recruiting multiple Rab GTPases and their cognate effectors to the inclusion. We demonstrate that CT229 specifically modulates clathrin-coated vesicle trafficking and regulates the trafficking of transferrin and the mannose-6-phosphate receptor, both of which are crucial for proper chlamydial development. This study highlights CT229 as a master regulator of multiple host vesicular trafficking pathways essential for chlamydial infection.