Bacteria hijack integrin-linked kinase to stabilize focal adhesions and block cell detachment
Bacteria hijack integrin-linked kinase to stabilize focal adhesions and block cell detachment
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DOI：
10.1038/nature07952
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发表时间：
2009-05-28
期刊：
影响因子：
64.8
通讯作者：
Sasakawa, Chihiro
中科院分区：
文献类型：
--
作者：
Kim, Minsoo;Ogawa, Michinaga;Sasakawa, Chihiro
粘膜上皮细胞的快速周转和脱落为抵抗细菌感染提供了一种天生的防御系统(1，2)。然而，包括志贺氏菌在内的许多致病菌能够有效地克服脱落并在上皮细胞上定植(3，4)。在这里，我们展示了志贺氏菌效应子OSPE(5，6)(由OspE1和OspE2蛋白组成)，它在致病性大肠杆菌、肠出血性大肠杆菌、罗氏柠檬酸杆菌和沙门氏菌中高度保守(7)，通过与整合素连接激酶(ILK)(8)相互作用加强宿主细胞对基底膜的黏附。ILK-OSPE结合后，随着膜分数ilk的增加，焦点粘附数增加。ILK和OSPE之间的相互作用增加了细胞表面β1整合素的水平，抑制了粘着斑激酶和帕西林的磷酸化，这是细胞运动中粘着斑快速转换所必需的(9)。OSPE的表达可阻断诺可达唑洗脱诱导的灶性粘连解离。缺乏OSPE基因的志贺氏菌突变体感染的极化上皮细胞比感染野生型志贺氏菌的细胞更快地脱离细胞。豚鼠结肠感染志贺氏菌证实了OSPE-ILK相互作用在抑制上皮脱落、增加细菌细胞间扩散和促进细菌定植方面的关键作用。这些结果表明，志贺氏菌通过使用特殊的策略来防止感染细胞脱落，从而维持其感染立足点。
The rapid turnover and exfoliation of mucosal epithelial cells provides an innate defence system against bacterial infection(1,2). Nevertheless, many pathogenic bacteria, including Shigella, are able to surmount exfoliation and colonize the epithelium efficiently(3,4). Here we show that the Shigella flexneri effector OspE(5,6) (consisting of OspE1 and OspE2 proteins), which is highly conserved among enteropathogenic Escherichia coli, enterohaemorrhagic E. coli, Citrobacter rodentium and Salmonella strains(7), reinforces host cell adherence to the basement membrane by interacting with integrin-linked kinase (ILK)(8). The number of focal adhesions was augmented along with membrane fraction ILK by ILK-OspE binding. The interaction between ILK and OspE increased cell surface levels of beta 1 integrin and suppressed phosphorylation of focal adhesion kinase and paxillin, which are required for rapid turnover of focal adhesion in cell motility(9). Nocodazole-washout-induced focal adhesion disassembly was blocked by expression of OspE. Polarized epithelial cells infected with a Shigella mutant lacking the ospE gene underwent more rapid cell detachment than cells infected with wild-type Shigella. Infection of guinea pig colons with Shigella corroborated the pivotal role of the OspE-ILK interaction in suppressing epithelial detachment, increasing bacterial cell-to-cell spreading, and promoting bacterial colonization. These results indicate that Shigella sustain their infectious foothold by using special tactics to prevent detachment of infected cells.