Helicobacter Host Interactions in Animal Models

动物模型中螺杆菌与宿主的相互作用

• 批准号: 6364973
• 负责人: STANLEY FALKOW
• 金额: $ 29.39万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6364973
• 关键词: Helicobacter; bacterial disease; bacterial genetics; cell motility; disease /disorder model; gene mutation; genetic library; genetic transcription; gerbil /jird; host organism interaction; immunocytochemistry; immunogenetics; infection related neoplasm /cancer; interleukin 8; laboratory mouse; lymphoma; microarray technology; microorganism immunology; neoplasm /cancer genetics; neoplasm /cancer immunology; neoplasm /cancer remission /regression; neoplastic process; polymerase chain reaction; transposon /insertion element

DESCRIPTION (provided by applicant): Helicobacter pylori infection is causally associated with gastritis and peptic ulcer, as well as two gastric malignancies, gastric carcinoma and B-cell-mucosa-associated lymphoid tissue (MALT) lymphoma. Our proposed research focuses on the application of genetic and molecular tools to manipulate the H. pylori chromosome and the use of DNA microarray technology to monitor both the host and the pathogen in H. pylori animal models of infection and disease. Specifically, we propose to examine the H. pylori infection of mice and Mongolian gerbil. While none of the cell culture models or the animal models we propose to use can fully reflect what is seen in humans, the mouse model of infection can be used to productively investigate how H. pylori colonizes the stomach. We wish to follow long-term infection of the mouse and the host cell response to long-term H. pylori carriage measured by transcriptional profile changes as compared to uninfected littermates. Also, the mouse infection model is useful to study one form of malignancy caused by H. pylori, MALT lymphoma, and we propose to study this feature of long-term H. pylori murine infection by both bacterial transcription profiling and by the use of a mouse DNA microarray to follow the host response and changes that occur in the malignant transformation. We also propose to identify bacterial genes essential for gastric colonization and persistence in the stomach using a method developed in our laboratory called MicroArray Transposon Tagging (MATT) strategy. H. pylori infection reflects a particularly intriguing example of a host-pathogen interaction. The microbe serves as a tool to understand host cell biology and malignancy. The response of the bacterium to the host cell environment allows us to understand the essence of bacterial pathogenicity.

描述（由申请人提供）：幽门螺杆菌感染是导致 与胃炎和消化性溃疡以及两种胃病有关 恶性肿瘤、胃癌和 B 细胞粘膜相关淋巴组织 （MALT）淋巴瘤。我们提出的研究重点是遗传的应用 和分子工具来操纵幽门螺杆菌染色体和 DNA 的使用 微阵列技术监测幽门螺杆菌的宿主和病原体 感染和疾病的动物模型。具体来说，我们建议审查 小鼠和蒙古沙鼠的幽门螺杆菌感染。虽然我们建议使用的细胞培养模型或动物模型都不能完全反映什么是 在人类中观察到，小鼠感染模型可有效地用于 研究幽门螺杆菌如何在胃中定殖。我们希望跟踪小鼠的长期感染以及宿主细胞对长期幽门螺杆菌的反应 与未感染者相比，通过转录谱变化测量携带情况 同窝的。此外，小鼠感染模型可用于研究一种形式的感染 幽门螺杆菌引起的恶性肿瘤，MALT淋巴瘤，我们建议通过细菌转录来研究长期幽门螺杆菌感染小鼠的这一特征 分析并使用小鼠 DNA 微阵列来跟踪宿主反应 以及恶变时发生的变化。我们还建议 鉴定胃定植和持续存在所必需的细菌基因 使用我们实验室开发的一种称为微阵列的方法来检测胃 转座子标记（MATT）策略。幽门螺杆菌感染反映了宿主与病原体相互作用的一个特别有趣的例子。微生物作为工具 了解宿主细胞生物学和恶性肿瘤。细菌的反应 对宿主细胞环境的了解使我们能够了解细菌的本质 致病性。