The intracellular bacterium Orientia tsutsugamushi uses the autotransporter ScaC to activate BICD1 and BICD2 adaptors for dynein-based motility.

The intracellular bacterium Orientia tsutsugamushi relies on the microtubule cytoskeleton and the motor protein dynein to traffic to the perinuclear region within infected cells. However, it remains unclear how the bacterium is coupled to the dynein machinery and how transport is regulated. Here, we discover that O. tsutsugamushi uses its autotransporter protein ScaC to recruit the dynein adaptors BICD1 and BICD2 for movement to the perinucleus. We show that ScaC is sufficient to engage dynein-based motility in the absence of other bacterial proteins and that BICD1 and BICD2 are required for efficient movement of O. tsutsugamushi during infection. Using TIRF single-molecule assays, we demonstrate that ScaC induces BICD2 to adopt an open conformation which activates the assembly of dynein-dynactin complexes. Our results reveal a novel role for BICD adaptors during bacterial infection and provide mechanistic insights into the life cycle of an important human pathogen.胞内细菌恙虫病东方体（Orientia tsutsugamushi）依赖微管细胞骨架（microtubule cytoskeleton）与动力蛋白（dynein），在感染的宿主细胞内完成向核周区域的转运。然而，该细菌如何与动力蛋白转运系统耦联，以及转运过程的调控机制，目前仍不明确。本研究发现，恙虫病东方体通过其自转运蛋白（autotransporter protein）ScaC招募动力蛋白适配因子（dynein adaptors）BICD1与BICD2，从而介导向核周区域的移动；实验表明，即便缺乏其他细菌蛋白，ScaC即可介导依赖动力蛋白的转运过程，且在感染期间，BICD1与BICD2对于恙虫病东方体的有效转运不可或缺。借助全内反射荧光显微镜（TIRF）单分子实验，我们证实ScaC可诱导BICD2形成开放构象，进而激活动力蛋白-动力激活蛋白复合物（dynein-dynactin complexes）的组装。本研究揭示了BICD适配因子在细菌感染过程中的全新功能，并为这一重要人类致病菌的生命周期提供了机制层面的深入见解。