Many cytosolic bacterial pathogens hijack the host actin polymerization machinery to form actin tails that promote direct cell-to-cell spread, enabling these pathogens to avoid extracellular immune defenses. However, these pathogens are still susceptible to intracellular cell-autonomous immune responses that restrict bacterial actin-based motility. Two classes of cytosolic antimotility factors, septins and guanylate-binding proteins (GBPs), have recently been established to block actin tail formation by the human-adapted bacterial pathogen Shigella flexneri. Both septin cages and GBP1 microcapsules restrict S. flexneri cell-to-cell spread by blocking S. flexneri actin-based motility. While septins assemble into cage-like structures around immobile S. flexneri, GBP1 forms microcapsules around both motile and immobile bacteria. The interplay between these two defense programs remains elusive. Here, we demonstrate that GBP1 microcapsules block septin cage assembly, likely by interfering with the function of S. flexneri IcsA, the outer membrane protein that promotes actin-based motility, as this protein is required for septin cage formation. However, S. flexneri that escape from GBP1 microcapsules via the activity of IpaH9.8, a type III secreted effector that promotes the degradation of GBPs, are often captured within septin cages. Thus, our studies reveal how septin cages and GBP1 microcapsules represent complementary host cell antimotility strategies.

中文翻译：

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GBP1 微胶囊干扰了福氏志贺氏菌周围 IcsA 依赖的化粪池组装

许多细胞溶质细菌病原体劫持宿主肌动蛋白聚合机制，形成肌动蛋白尾巴，促进细胞间直接传播，使这些病原体能够避免细胞外免疫防御。然而，这些病原体仍然容易受到限制细菌肌动蛋白运动的细胞内细胞自主免疫反应的影响。最近已经建立了两类细胞溶质抗运动因子，败血素和鸟苷酸结合蛋白 (GBP)，以阻止人类适应的细菌病原体福氏志贺菌形成肌动蛋白尾。septin 笼和 GBP1 微胶囊都通过阻断基于 S. flexneri 肌动蛋白的运动来限制 S. flexneri 细胞间的传播。当化粪池在不动的 S. flexneri 周围组装成笼状结构时，GBP1 在能动和不动的细菌周围形成微囊。这两个防御计划之间的相互作用仍然难以捉摸。在这里，我们证明 GBP1 微胶囊阻断化粪池组装，可能是通过干扰 S. flexneri IcsA 的功能，这是一种促进基于肌动蛋白的运动的外膜蛋白，因为这种蛋白质是化粪池形成所必需的。然而，通过 IpaH9.8（一种促进 GBP 降解的 III 型分泌效应器）的活性从 GBP1 微囊中逃逸的 S. flexneri 通常被捕获在化粪池中。因此，我们的研究揭示了 septin 笼和 GBP1 微胶囊如何代表互补的宿主细胞抗运动策略。促进基于肌动蛋白的运动的外膜蛋白，因为这种蛋白是化粪池形成所必需的。然而，通过 IpaH9.8（一种促进 GBP 降解的 III 型分泌效应器）的活性从 GBP1 微囊中逃逸的 S. flexneri 通常被捕获在化粪池中。因此，我们的研究揭示了 septin 笼和 GBP1 微胶囊如何代表互补的宿主细胞抗运动策略。促进基于肌动蛋白的运动的外膜蛋白，因为这种蛋白是化粪池形成所必需的。然而，通过 IpaH9.8（一种促进 GBP 降解的 III 型分泌效应器）的活性从 GBP1 微囊中逃逸的 S. flexneri 通常被捕获在化粪池中。因此，我们的研究揭示了 septin 笼和 GBP1 微胶囊如何代表互补的宿主细胞抗运动策略。