Cyclophilin A Controls Salmonella Internalization Levels and is Present at E. coli Actin-Rich Pedestals
Cyclophilin A Controls Salmonella Internalization Levels and is Present at E. coli Actin-Rich Pedestals
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DOI：
10.1002/ar.23957
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发表时间：
2018-12-01
影响因子：
2
通讯作者：
Guttman, Julian A.
中科院分区：
文献类型：
--
作者：
Dhanda, Aaron S.;Warren, Kiera E.;Guttman, Julian A.
肠道沙门氏菌鼠伤寒血清型（S.鼠伤寒沙门氏菌（Typhimurium）、肠致病性大肠杆菌（EPEC）和肠出血性E.大肠杆菌（EHEC）在其感染过程中占据宿主细胞的肌动蛋白细胞骨架作为关键步骤。这些病原体依赖于将其自身的效应物直接注射到靶宿主细胞中，以便篡夺导致这些细胞中的形态肌动蛋白重排的细胞信号传导途径。在这里，我们表明，PPIase亲环素A（CypA）是一个新的组成部分，S。Typhimurium诱导的膜皱褶和功能限制细菌侵入水平，如在CypA耗尽的细胞中，细菌负荷增加。我们还表明，CypA需要EPEC效应Tir以及基座的形成，其招聘到细菌附着位点，它的存在也在肠出血性大肠杆菌感染期间，在肠道。最后，我们证明，CypA被发现在板状伪足，肌动蛋白丰富的结构在运动细胞的前缘。我们的研究结果进一步确立CypA作为细菌感染期间和一般细胞内形成的动态肌动蛋白丰富结构的组成部分。(C)2018年威利期刊公司
Salmonella enterica serovar Typhimurium (S. Typhimurium), enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) commandeer the actin cytoskeleton of their host cells as a crucial step in their infectious processes. These pathogens depend on the injection of their own effectors directly into target host cells in order to usurp cellular signaling pathways that lead to morphological actin rearrangements in those cells. Here we show that the PPIase Cyclophilin A (CypA) is a novel component of S. Typhimurium-induced membrane ruffles and functions to restrict bacterial invasion levels, as in cells depleted of CypA, bacterial loads increase. We also demonstrate that CypA requires the EPEC effector Tir as well as pedestal formation for its recruitment to bacterial attachment sites and that its presence at pedestals also holds during EHEC infections. Finally, we demonstrate that CypA is found at lamellipodia; actin-rich structures at the leading edge of motile cells. Our findings further establish CypA as a component of dynamic actin-rich structures formed during bacterial infections and within cells in general. (C) 2018 Wiley Periodicals, Inc.