PDF(Pubmed)
Abstract：
Chlamydia trachomatis (C.t.), the leading cause of bacterial sexually transmitted infections, employs a type III secretion system (T3SS) to translocate two classes of effectors, inclusion membrane proteins and conventional T3SS (cT3SS) effectors, into the host cell to counter host defense mechanisms. Here we employed three assays to directly evaluate secretion during infection, validating secretion for 23 cT3SS effectors. As bioinformatic analyses have been largely unrevealing, we conducted affinity purification-mass spectrometry to identify host targets and gain insights into the functions of these effectors, identifying high confidence interacting partners for 21 cT3SS effectors. We demonstrate that CebN localizes to the nuclear envelope in infected and bystander cells where it interacts with multiple nucleoporins and Rae1, blocking STAT1 nuclear import following IFN-γ stimulation. By building a cT3SS effector-host interactome, we have identified novel pathways that are targeted during bacterial infection and have begun to address how C.t. effectors combat cell autonomous immunity.
摘要：
沙眼衣原体（C.t.),细菌性性传播感染的主要原因，使用III型分泌系统（T3SS）来移位两类效应物，包涵膜蛋白和常规T3SS（cT3SS）效应子，进入宿主细胞以对抗宿主防御机制。在这里，我们采用了三种方法来直接评估感染过程中的分泌，验证23个cT3SS效应子的分泌。由于生物信息学分析在很大程度上没有揭示，我们进行了亲和纯化-质谱来识别宿主靶标并深入了解这些效应子的功能，确定21个cT3SS效应器的高置信度交互伙伴。我们证明，CebN定位于受感染和旁观者细胞的核膜，在那里它与多个核孔蛋白和Rae1相互作用，在IFN-γ刺激后阻断STAT1核输入。通过构建cT3SS效应-宿主相互作用组，我们已经确定了在细菌感染过程中靶向的新通路，并开始研究C.t.效应子如何对抗细胞自主免疫。
