Analysis of the H. Pylori cag pathogenicity island

幽门螺杆菌cag致病岛分析

• 批准号: 7795254
• 负责人: TIMOTHY L COVER
• 金额: $ 37.99万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-15 至 2013-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7795254
• 关键词: Animal Model; Bacteria; Bacterial Infections; DNA; Development; Disease; Epithelial Cells; Exhibits; Gastric mucosa; Genetic Variation; Goals; Gram-Negative Bacteria; Helicobacter Infections; Helicobacter pylori; Human; In Vitro; Incidence; Individual; Lead; Molecular; Pathogenicity Island; Peptic Ulcer; Peptidoglycan; Persons; Prevention; Proteins; Research; Research Design; Risk Factors; Stomach; Stomach Diseases; System; Type IV Secretion System Pathway; Ulcer; Work; malignant stomach neoplasm; secretion process

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.

描述（由申请人提供）：用革兰氏阴性细菌幽门螺杆菌对人胃的持续定殖是胃癌和消化性溃疡疾病发展的危险因素。这项工作的长期目标是了解幽门螺杆菌引起这些疾病的分子机制，并为预防和治疗这些疾病开发有效手段。来自不同人类的幽门螺杆菌分离株表现出相当多的遗传多样性。 CAG致病岛（PAI）是一个40 kb的区域，预计将编码27种不同的蛋白质。感染CAG PAI阳性菌株的人中，有症状的胃杀伤性疾病（胃癌或消化性溃疡）的发生率高于感染CAG阴性菌株的人。 CAG PAI编码通过IV型分泌过程将CAGA转移到胃皮细胞中的效应蛋白，CAGA和多种蛋白质。该项目描述了研究CAGA转移到胃皮细胞中的分子机制的计划。该项目的目的是i）分析CAG PAI编码IV型分泌设备的子仪器； ii）研究幽门螺杆菌CAG蛋白的亚细胞定位； iii）分析CAGA在动物模型的胃中的影响。这些研究应导致我们对幽门螺杆菌h. cag pai的产物有助于胃杀伤性疾病发展的分子机制的理解的重要进展。人类胃中称为幽门螺杆菌的细菌的存在有助于胃癌和消化性溃疡疾病的发展。这项研究试图了解细菌感染如何导致这些疾病。长期目标是为预防和治疗胃癌和消化性溃疡病的有效手段。