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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 客观的： 幽门螺杆菌是一种常见的胃部感染细菌，它会导致所有个体出现炎症（胃炎），并导致某些人出现消化性溃疡或胃癌。与胃癌和消化性溃疡发展相关的最深入研究的细菌因素是细胞毒素相关基因致病岛（cag PAI）。虽然幽门螺杆菌 cag PAI 的细胞生物学已在体外进行了广泛研究，但其在体内的作用却知之甚少。我们最近使用恒河猴模型来证明幽门螺杆菌以 cag PAI 依赖性方式诱导抗菌宿主反应，其中包括胃粘膜中一系列先天免疫效应分子的上调。虽然幽门螺杆菌携带刺激抗菌宿主防御的遗传元件似乎有些矛盾，但幽门螺杆菌可能比其他胃居民对这些效应物具有更强的抵抗力，因此在发炎的胃中享有竞争优势。相反，已建立的微生物群落与宿主之间的相互作用可能会调节幽门螺杆菌的成功定殖。我们的具体目标是：(a) 描述恒河猴​​胃部微生物群落的特征，并比较野生型幽门螺杆菌或其同基因 cag PAI 敲除的感染效果，以及 (b) 确定减少幽门螺杆菌感染的效果。胃微生物群落对幽门螺杆菌感染的影响。这些研究将有助于我们了解宿主和常驻微生物群之间的相互作用，以及微生物群落成员之间的对抗关系，这可能会加剧或减轻病原体对宿主的影响。