Department of Clinical Bacteriology, Nice University Hospital, 151 Route de Saint Antoine de Ginestière, 06202 Nice Cedex 03, France.
Trends Microbiol. 2012 Apr;20(4):165-74. doi: 10.1016/j.tim.2012.01.008. Epub 2012 Feb 23.
VacA toxin from the cancer-inducing bacterium Helicobacter pylori is currently classified as a pore-forming toxin but is also considered a multifunctional toxin, apparently causing many pleiotropic cell effects. However, an increasing body of evidence suggests that VacA could be the prototype of a new class of monofunctional A-B toxins in which the A subunit exhibits pore-forming instead of enzymatic activity. Thus, VacA may use a peculiar mechanism of action, allowing it to intoxicate the human stomach. By combining the action of a cell-binding domain, a specific intracellular trafficking pathway and a novel mitochondrion-targeting sequence, the VacA pore-forming domain is selectively delivered to the inner mitochondrial membrane to efficiently kill target epithelial cells by apoptosis.
来自致癌细菌幽门螺旋杆菌的 VacA 毒素目前被归类为孔形成毒素，但也被认为是一种多功能毒素，显然会导致许多多效性的细胞效应。然而，越来越多的证据表明，VacA 可能是新型单功能 A-B 毒素的原型，其中 A 亚基表现出孔形成而不是酶活性。因此，VacA 可能使用一种特殊的作用机制，使其能够使人类胃部中毒。通过结合细胞结合结构域、特定的细胞内运输途径和新型的线粒体靶向序列的作用，VacA 的孔形成结构域被选择性递送至线粒体内膜，通过细胞凋亡有效地杀死靶上皮细胞。
