Role of the cag-pathogenicity island encoded type IV secretion system in Helicobacter pylori pathogenesis.
Role of the cag-pathogenicity island encoded type IV secretion system in Helicobacter pylori pathogenesis.
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DOI：
10.1111/j.1742-4658.2011.08035.x
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发表时间：
2011-04
期刊：
影响因子：
--
通讯作者：
Backert S
中科院分区：
文献类型：
--
作者：
Tegtmeyer N;Wessler S;Backert S
幽门螺杆菌是世界范围内非常成功的人类特异性细菌。这种病原体感染胃可引起包括慢性胃炎、消化性溃疡甚至胃癌在内的病理。高毒力H. pylori菌株编码cag（细胞毒素相关基因）致病岛，其表达IV型分泌系统（T4SS）。这种T4SS形成了一种类似于螺旋藻的菌毛结构，用于将毒力因子如CagA效应蛋白注射到宿主靶细胞中。这是通过许多T4SS蛋白实现的，包括CagI、CagL、CagY和CagA，其本身结合宿主细胞整联蛋白成员β1，随后递送CagA穿过宿主细胞膜。CagA与磷脂酰丝氨酸相互作用的作用也已被证明对注射过程是重要的。递送后，CagA被致癌酪氨酸激酶磷酸化，并模拟宿主细胞因子，用于激活或失活某些特定的细胞内信号传导途径。在这里，我们回顾了最近的进展，在表征CagA依赖和CagA非依赖的信号转导能力的T4 SS，其中包括膜动力学的诱导，细胞间连接的破坏，肌动蛋白细胞骨架重排以及促炎，细胞周期相关和抗凋亡的转录反应。这些信号通路在H.幽门螺杆菌感染进行了讨论。
Helicobacter pylori is a very successful human-specific bacterium worldwide. Infections of the stomach with this pathogen can induce pathologies including chronic gastritis, peptic ulcers and even gastric cancer. Highly virulent H. pylori strains encode the cag (cytotoxin-associated genes) pathogenicity island which expresses a type IV secretion system (T4SS). This T4SS forms a syringe-like pilus structure for the injection of virulence factors such as the CagA effector protein into host target cells. This is achieved by a number of T4SS proteins including CagI, CagL, CagY and CagA which by itself bind the host cell integrin member β1 followed by delivery of CagA across the host cell membrane. A role of CagA interaction with phosphatidylserine has also been shown to be important for the injection process. After delivery, CagA becomes phosphorylated by oncogenic tyrosine kinases and mimics a host cell factor for the activation or inactivation of some specific intracellular signaling pathways. Here we review recent progress in characterizing CagA-dependent and CagA-independent signalling capabilities of the T4SS which include the induction of membrane dynamics, disruption of cell-to-cell junctions, actin-cytoskeletal rearrangements as well as pro-inflammatory, cell cycle-related and anti-apoptotic transcriptional responses. The contribution of these signalling pathways to pathogenesis during H. pylori infections is discussed.
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