Department of Microbiology and Molecular Genetics, Institute of Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Cell Microbiol. 2010 Apr 1;12(4):489-505. doi: 10.1111/j.1462-5822.2009.01410.x. Epub 2009 Nov 12.
Enterohaemorrhagic Escherichia coli and enteropathogenic E. coli are enteropathogens characterized by their ability to induce the host cell to form actin-rich structures, termed pedestals. A type III secretion system, through which the pathogens deliver effector proteins into infected host cells, is essential for their virulence and pedestal formation. Enterohaemorrhagic E. coli encodes two similar effectors, EspM1 and EspM2, which activate the RhoA signalling pathway and induce the formation of stress fibres upon infection of host cells. We confirm these observations and in addition show that EspM inhibits the formation of actin pedestals. Moreover, we show that translocation of EspM into polarized epithelial cells induces dramatic changes in the tight junction localization and in the morphology and architecture of infected polarized monolayers. These changes are manifested by altered localization of the tight junctions and 'bulging out' morphology of the cells. Surprisingly, despite the dramatic changes in their architecture, the cells remain alive and the epithelial monolayer maintains a normal barrier function. Taken together, our results show that the EspM effectors inhibit pedestal formation and induce tight junction mislocalization as well as dramatic changes in the architecture of the polarized monolayer.
产肠毒性大肠杆菌和肠致病性大肠杆菌是具有诱导宿主细胞形成富含肌动蛋白结构（称为基脚）能力的肠病原体。III 型分泌系统是病原体将效应蛋白递送至感染宿主细胞所必需的，对于它们的毒力和基脚形成至关重要。产肠毒性大肠杆菌编码两种类似的效应蛋白 EspM1 和 EspM2，它们激活 RhoA 信号通路，并在感染宿主细胞时诱导应激纤维的形成。我们证实了这些观察结果，并进一步表明 EspM 抑制肌动蛋白基脚的形成。此外，我们表明 EspM 易位到极化上皮细胞中会诱导紧密连接定位以及感染极化单层的形态和结构的剧烈变化。这些变化表现为紧密连接的定位改变和细胞的“膨出”形态。令人惊讶的是，尽管它们的结构发生了剧烈变化，但细胞仍然存活，上皮单层保持正常的屏障功能。总之，我们的结果表明 EspM 效应蛋白抑制基脚形成，并诱导紧密连接定位错误以及极化单层结构的剧烈变化。
