Analysis of the H. Pylori cag pathogenicity island

描述（由申请人提供）：革兰氏阴性杆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展的危险因素。本工作的长期目标是了解幽门螺旋杆菌引起这些疾病的分子机制，并为预防和治疗这些疾病制定有效的手段。来自不同人类的幽门螺杆菌分离株表现出相当程度的遗传多样性。一个存在于某些幽门螺杆菌菌株而不存在于其他菌株的染色体区域是cag致病性岛（PAI），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）的发生率在感染cag pai阳性菌株的人群中高于感染cag pai阴性菌株的人群。cag PAI编码一种效应蛋白、CagA和多种通过IV型分泌过程将CagA转运到胃上皮细胞的蛋白。本项目计划研究CagA转运到胃上皮细胞的分子机制。该项目的目的是i)分析cag pai编码的IV型分泌装置的子组件；ii)研究幽门螺杆菌Cag蛋白的亚细胞定位；iii)分析CagA对动物模型胃的影响。这些研究将在我们理解幽门螺杆菌cag PAI产物促进胃十二指肠疾病发展的分子机制方面取得重要进展。人类胃中存在一种被称为幽门螺杆菌的细菌，会导致胃癌和消化性溃疡疾病的发生。这项研究旨在了解细菌感染如何导致这些疾病。长期目标是开发预防和治疗胃癌和消化性溃疡疾病的有效手段。

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.