HELICOBACTER PYLORI AND THE GASTRIC MICROBIAL COMMUNITY IN RHESUS MACAQUES

恒河猴中的幽门螺杆菌和胃微生物群落

• 批准号: 8357316
• 负责人: JAY V. SOLNICK
• 金额: $ 7.56万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357316
• 关键词: Anti-Bacterial Agents; Bacteria; California; Cellular biology; Cytotoxin; Development; Funding; Gastric mucosa; Gastritis; Genes; Goals; Grant; Helicobacter pylori; Host Defense; Immune; Immune response; In Vitro; Individual; Infection; Inflammation; Knock-out; Macaca mulatta; Modeling; National Center for Research Resources; Pathogenicity Island; Peptic Ulcer; Primates; Principal Investigator; Research; Research Infrastructure; Resistance; Resources; Source; Stomach; United States National Institutes of Health; Up-Regulation; antimicrobial; cost; genetic element; in vivo; malignant stomach neoplasm; member; microbial community; pathogen

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: Helicobacter pylori is a bacterium that commonly infects the stomach, where it causes inflammation (gastritis) in all individuals and peptic ulcer disease or gastric cancer in some. The most intensively studied bacterial factor associated with the development of gastric cancer and peptic ulcer is the cytotoxin-associated gene pathogenicity island (cag PAI). While the cell biology of the H. pylori cag PAI has been studied extensively in vitro, its effects in vivo are poorly understood. We recently used the rhesus macaque model to demonstrate that H. pylori induces an antimicrobial host response in a cag PAI-dependent manner, which includes up-regulation of a suite of innate immune effectors molecules in the gastric mucosa. While it seems paradoxical that H. pylori would carry a genetic element that stimulates anti-bacterial host defenses, it is possible that H. pylori is more resistant to these effectors than other gastric inhabitants, and thus enjoys a competitive advantage in the inflamed stomach. Conversely, interactions between an established microbial community and the host may modulate successful colonization by H. pylori. Our specific goals are to: (a) characterize the microbial community of the stomach in the rhesus macaque and compare the effects of infection with wild-type H. pylori or its isogenic cag PAI knockout, and (b) determine the effects of reducing the gastric microbial community on infection with H. pylori. These studies will contribute to our understanding of the interplay between the host and resident microbiota, as well as antagonistic relationships between members of microbial communities, which may intensify or mitigate the impact of a pathogen on the host.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 目的： 幽门螺杆菌是一种常见的感染胃的细菌，在所有个体中引起炎症（胃炎），在一些个体中引起消化性溃疡疾病或胃癌。细胞毒素相关基因致病岛（cag派）是研究最多的与胃癌和消化性溃疡发生相关的细菌因子。而H. pylori cag派已在体外被广泛研究，但其在体内的作用知之甚少。我们最近使用恒河猴模型来证明H。幽门螺杆菌以cag PAI依赖性方式诱导抗微生物宿主应答，其包括胃粘膜中一组先天免疫效应分子的上调。虽然H.幽门螺杆菌携带一种基因元件，刺激抗细菌宿主防御，这是可能的，H。幽门比其它胃内生物对这些效应物更有抵抗力，因此在发炎的胃中具有竞争优势。相反，已建立的微生物群落和宿主之间的相互作用可能调节H.幽门。我们的具体目标是：（a）表征恒河猴胃中的微生物群落，并比较用野生型H. pylori或其同基因cag派敲除，和（B）确定减少胃微生物群落对H.幽门。这些研究将有助于我们了解宿主和居民微生物群之间的相互作用，以及微生物群落成员之间的拮抗关系，这可能会加强或减轻病原体对宿主的影响。