PDF(Pubmed)
Abstract：
The Gram-negative bacterium Helicobacter pylori is a very successful pathogen, one of the most commonly identified causes of bacterial infections in humans worldwide. H. pylori produces several virulence factors that contribute to its persistence in the hostile host habitat and to its pathogenicity. The most extensively studied are cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA). VacA is present in almost all H. pylori strains. As a secreted multifunctional toxin, it assists bacterial colonization, survival, and proliferation during long-lasting infections. To exert its effect on gastric epithelium and other cell types, VacA undergoes several modifications and crosses multiple membrane barriers. Once inside the gastric epithelial cell, VacA disrupts many cellular-signaling pathways and processes, leading mainly to changes in the efflux of various ions, the depolarization of membrane potential, and perturbations in endocytic trafficking and mitochondrial function. The most notable effect of VacA is the formation of vacuole-like structures, which may lead to apoptosis. This review focuses on the processes involved in VacA secretion, processing, and entry into host cells, with a particular emphasis on the interaction of the mature toxin with host membranes and the formation of transmembrane pores.
摘要：
革兰氏阴性细菌幽门螺杆菌是一种非常成功的病原体，世界范围内人类细菌感染的最常见原因之一。幽门螺杆菌产生几种毒力因子，这些毒力因子有助于其在敌对宿主栖息地中的持久性和致病性。研究最广泛的是细胞毒素相关基因A（CagA）和空泡细胞毒素A（VacA）。VacA存在于几乎所有的幽门螺杆菌菌株中。作为一种分泌的多功能毒素，它有助于细菌定植，生存,和长期感染期间的增殖。为了发挥其对胃上皮和其他细胞类型的作用，VacA经历了几次修改并穿过多个膜屏障。一旦进入胃上皮细胞，VacA破坏许多细胞信号通路和过程，主要导致各种离子流出的变化，膜电位的去极化，以及胞吞运输和线粒体功能的扰动。VacA最显着的作用是形成液泡状结构，这可能导致细胞凋亡。这篇综述集中在VacA分泌过程中，processing,进入宿主细胞，特别强调成熟毒素与宿主膜的相互作用和跨膜孔的形成。
