Lim Jenson, Stones Daniel H, Hawley Catherine Alice, Watson Charlie Anne, Krachler Anne Marie
Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
PLoS Pathog. 2014 Sep 25;10(9):e1004421. doi: 10.1371/journal.ppat.1004421. eCollection 2014 Sep.
Vibrio parahaemolyticus is an emerging bacterial pathogen which colonizes the gastrointestinal tract and can cause severe enteritis and bacteraemia. During infection, V. parahaemolyticus primarily attaches to the small intestine, where it causes extensive tissue damage and compromises epithelial barrier integrity. We have previously described that Multivalent Adhesion Molecule (MAM) 7 contributes to initial attachment of V. parahaemolyticus to epithelial cells. Here we show that the bacterial adhesin, through multivalent interactions between surface-induced adhesin clusters and phosphatidic acid lipids in the host cell membrane, induces activation of the small GTPase RhoA and actin rearrangements in host cells. In infection studies with V. parahaemolyticus we further demonstrate that adhesin-triggered activation of the ROCK/LIMK signaling axis is sufficient to redistribute tight junction proteins, leading to a loss of epithelial barrier function. Taken together, these findings show an unprecedented mechanism by which an adhesin acts as assembly platform for a host cellular signaling pathway, which ultimately facilitates breaching of the epithelial barrier by a bacterial pathogen.
副溶血性弧菌是一种新出现的细菌病原体，它定殖于胃肠道，可引起严重肠炎和菌血症。在感染过程中，副溶血性弧菌主要附着于小肠，在那里它会造成广泛的组织损伤并破坏上皮屏障的完整性。我们之前曾描述过，多价粘附分子（MAM）7有助于副溶血性弧菌最初附着于上皮细胞。在此我们表明，这种细菌粘附素通过表面诱导的粘附素簇与宿主细胞膜中的磷脂酸脂质之间的多价相互作用，诱导宿主细胞中小GTP酶RhoA的激活和肌动蛋白重排。在用副溶血性弧菌进行的感染研究中，我们进一步证明，粘附素触发的ROCK/LIMK信号轴激活足以重新分布紧密连接蛋白，导致上皮屏障功能丧失。综上所述，这些发现揭示了一种前所未有的机制，即粘附素作为宿主细胞信号通路的组装平台，最终促进细菌病原体突破上皮屏障。
