Division of Infectious Diseases, Brigham and Women's Hospital, 15 Francis Street, Boston, MA 02115, USA.
Cell Rep. 2013 May 30;3(5):1690-702. doi: 10.1016/j.celrep.2013.03.039. Epub 2013 Apr 25.
Vibrio parahaemolyticus type III secretion system 2 (T3SS2) is essential for the organism's virulence, but the effectors required for intestinal colonization and induction of diarrhea by this pathogen have not been identified. Here, we identify a type III secretion system (T3SS2)-secreted effector, VopZ, that is essential for V. parahaemolyticus pathogenicity. VopZ plays distinct, genetically separable roles in enabling intestinal colonization and diarrheagenesis. Truncation of VopZ prevents V. parahaemolyticus colonization, whereas deletion of VopZ amino acids 38-62 abrogates V. parahaemolyticus-induced diarrhea and intestinal pathology but does not impair colonization. VopZ inhibits activation of the kinase TAK1 and thereby prevents the activation of MAPK and NF-κB signaling pathways, which lie downstream. In contrast, the VopZ internal deletion mutant cannot counter the activation of pathways regulated by TAK1. Collectively, our findings suggest that VopZ's inhibition of TAK1 is critical for V. parahaemolyticus to induce diarrhea and intestinal pathology.
副溶血性弧菌 III 型分泌系统 2（T3SS2）对该生物体的毒力至关重要，但尚未鉴定出该病原体进行肠道定植和诱导腹泻所需的效应物。在这里，我们鉴定了一种 III 型分泌系统（T3SS2）分泌的效应物 VopZ，它是副溶血性弧菌致病性所必需的。VopZ 在使肠道定植和致腹泻方面发挥着不同的、可遗传的作用。VopZ 的截断阻止了副溶血性弧菌的定植，而 VopZ 氨基酸 38-62 的缺失消除了副溶血性弧菌诱导的腹泻和肠道病理学，但不会损害定植。VopZ 抑制激酶 TAK1 的激活，从而防止 MAPK 和 NF-κB 信号通路的激活，后者位于下游。相比之下，VopZ 的内部缺失突变体不能抵消 TAK1 调节的途径的激活。总的来说，我们的研究结果表明，VopZ 对 TAK1 的抑制作用对于副溶血性弧菌诱导腹泻和肠道病理学至关重要。
