Interferon exposure boosts cell-autonomous immunity for more efficient pathogen control. But how interferon-enhanced immunity protects the cytosol against bacteria and how professionally cytosol-dwelling bacteria avoid clearance are insufficiently understood. Here we demonstrate that the interferon-induced GTPase family of guanylate-binding proteins (GBPs) coats Shigella flexneri in a hierarchical manner reliant on GBP1. GBPs inhibit actin-dependent motility and cell-to-cell spread of bacteria but are antagonized by IpaH9.8, a bacterial ubiquitin ligase secreted into the host cytosol. IpaH9.8 ubiquitylates GBP1, GBP2, and GBP4 to cause the proteasome-dependent destruction of existing GBP coats. This ubiquitin coating of Shigella favors the pathogen as it liberates bacteria from GBP encapsulation to resume actin-mediated motility and cell-to-cell spread. We conclude that an important function of GBP recruitment to S. flexneri is to prevent the spread of infection to neighboring cells while IpaH9.8 helps bacterial propagation by counteracting GBP-dependent cell-autonomous immunity.

干扰素暴露可增强细胞自主免疫，从而更有效地控制病原体。但是，干扰素增强的免疫力如何保护细胞质免受细菌侵害，以及细胞质内的细菌如何专业地避免清除，目前还没有得到充分了解。在这里，我们证明干扰素诱导的 GTPase 家族的鸟苷酸结合蛋白 (GBPs)以依赖于 GBP1 的分层方式覆盖福氏志贺氏菌。GBPs 抑制细菌的肌动蛋白依赖性运动和细胞间传播，但被 IpaH9.8 拮抗，IpaH9.8 是一种分泌到宿主细胞质中的细菌泛素连接酶。IpaH9.8 泛素化 GBP1、GBP2 和 GBP4，导致现有 GBP 涂层的蛋白酶体依赖性破坏。这种志贺氏菌的泛素涂层有利于病原体，因为它将细菌从 GBP 封装中释放出来，以恢复肌动蛋白介导的运动和细胞间传播。我们得出结论，GBP 募集到S. flexneri的一个重要功能是防止感染扩散到邻近细胞，而 IpaH9.8 通过抵消 GBP 依赖性细胞自主免疫来帮助细菌繁殖。