Analysis of the H. Pylori cag pathogenicity island

描述（由申请方提供）：革兰氏阴性菌幽门螺杆菌在人胃中的持续定植是胃癌和消化性溃疡疾病发生的风险因素。这项工作的长期目标是了解H。幽门螺杆菌导致这些疾病，并开发有效的手段来预防和治疗这些疾病。H.来自不同人的幽门螺杆菌分离物表现出相当程度的遗传多样性。在某些H染色体中存在的一个染色体区域。pylori菌株而不是其他菌株的一个重要的基因是cag致病岛（派），这是一个40 kb的区域，预计编码27种不同的蛋白质。有症状的胃十二指肠疾病（胃癌或消化性溃疡）的发病率在感染cag PAI阳性菌株的人中高于感染cag阴性菌株的人。cag派编码一种效应蛋白CagA和多种通过IV型分泌过程将CagA转运到胃上皮细胞中的蛋白。该项目描述了研究CagA转位到胃上皮细胞的分子机制的计划。本研究的目的是：i）分析cag PAI编码的IV型分泌器的结构; ii）研究H. pylori Cag蛋白;和iii）分析CagA在动物模型胃中的作用。这些研究将使我们对H。pylori cag派参与胃十二指肠疾病的发生发展。幽门螺杆菌是一种存在于人类胃中的细菌，它会导致胃癌和消化性溃疡的发生。这项研究旨在了解细菌感染如何导致这些疾病。长远目标是发展预防和治疗胃癌和消化性溃疡的有效方法。

DESCRIPTION (provided by applicant): Persistent colonization of the human stomach with the Gram negative bacterium Helicobacter pylori is a risk factor for the development of gastric cancer and peptic ulcer disease. The long-term goals of this work are to understand the molecular mechanisms by which H. pylori causes these diseases, and to develop effective means for the prevention and treatment of these diseases. H. pylori isolates from different humans exhibit a considerable level of genetic diversity. One chromosomal region that is present in some H. pylori strains but not others is the cag pathogenicity island (PAI), a 40 kb region that is predicted to encode 27 different proteins. The incidence of symptomatic gastroduodenal disease (gastric cancer or peptic ulceration) is higher among persons infected with cag PAI-positive strains than among persons infected with cag-negative strains. The cag PAI encodes an effector protein, CagA, and multiple proteins that translocate CagA into gastric epithelial cells via a type IV secretion process. This project describes plans to investigate the molecular mechanisms by which CagA is translocated into gastric epithelial cells. The aims of the project are i) to analyze subassemblies of the cag PAI-encoded type IV secretion apparatus; ii) to investigate the subcellular localization of H. pylori Cag proteins; and iii) to analyze effects of CagA in the stomachs of animal models. These studies should lead to important advances in our understanding of the molecular mechanisms by which products of the H. pylori cag PAI contribute to the development of gastroduodenal diseases. The presence of a bacterium known as Helicobacter pylori in the human stomach contributes to the development of cancer of the stomach and peptic ulcer disease. This research seeks to understand how a bacterial infection can lead to these diseases. The long-term goals are to develop effective means for the prevention and treatment of stomach cancer and peptic ulcer disease.