Division of Microbiology, Department of Biology, Friedrich Alexander University Erlangen-Nuremberg, Staudtstr. 5, Erlangen, 91058, Germany.
Max von Pettenkofer-Institute for Hygiene and Medical Microbiology, Ludwig-Maximilians-University, Munich, Germany.
Curr Top Microbiol Immunol. 2017;413:187-220. doi: 10.1007/978-3-319-75241-9_8.
Various gram-negative pathogens express type IV secretion systems (T4SSs) which translocate bacterial virulence factors into host target cells to hijack cellular processes for their own benefit and causing disease. The pathology of Helicobacter pylori, the causative agent of chronic gastritis, peptic ulcer disease, and gastric cancer in humans, strongly depends on a T4SS encoded by the cag pathogenicity island (cagPAI). This T4SS represents a pilus-like structure and a membrane-spanning complex. T4SS assembly is achieved by various protein-protein interactions and several pilus-associated components (CagL, CagI, CagY, and CagA) that allow docking to the host cell integrin member αβ followed by delivery of its major effector protein, CagA, across the host cell membrane. In addition, recent studies have shown that H. pylori exploits human CEACAM receptors via the adhesin HopQ, encoded outside of the cagPAI, for bacterial adherence and translocation of CagA. Here, we review the composition and assembly of the H. pylori T4SS and its fundamental role in the infection process. We discuss major CagA-dependent and CagA-independent signaling events by the T4SS in vitro and in animal models in vivo, which include the induction of cytoskeletal rearrangements, membrane dynamics, disturbance of cell polarity as well as transcriptional responses involved in inflammation, cell proliferation, and anti-apoptosis. The contribution of these signaling cascades to H. pylori colonization, and pathogenesis is reviewed.
多种革兰氏阴性病原体表达 IV 型分泌系统（T4SS），该系统将细菌毒力因子转位至宿主靶细胞，以劫持细胞过程为己所用，从而导致疾病。幽门螺杆菌是慢性胃炎、消化性溃疡病和胃癌的病原体，其病理学强烈依赖于 cag 致病岛（cagPAI）编码的 T4SS。该 T4SS 代表了一种类似于菌毛的结构和一个跨膜复合物。T4SS 的组装是通过各种蛋白-蛋白相互作用和几个菌毛相关成分（CagL、CagI、CagY 和 CagA）实现的，这些成分允许与宿主细胞整合素成员 αβ 对接，然后将其主要效应蛋白 CagA 递送至宿主细胞膜内。此外，最近的研究表明，幽门螺杆菌通过黏附素 HopQ 利用人类 CEACAM 受体，该黏附素编码于 cagPAI 之外，用于细菌黏附和 CagA 的易位。在这里，我们综述了幽门螺杆菌 T4SS 的组成和组装及其在感染过程中的基本作用。我们讨论了 T4SS 在体外和体内动物模型中主要的 CagA 依赖和 CagA 非依赖的信号事件，这些事件包括细胞骨架重排、膜动力学、细胞极性紊乱以及涉及炎症、细胞增殖和抗细胞凋亡的转录反应。我们还综述了这些信号级联反应对幽门螺杆菌定植和发病机制的贡献。
