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: 6634086
• 负责人: STANLEY FALKOW
• 金额: $ 29.4万
• 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/6634086
• 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）：幽门螺杆菌感染是因果关系 与胃炎和消化性溃疡，以及两个胃 恶性肿瘤、胃癌和B细胞粘膜相关淋巴组织 （MALT）淋巴瘤。我们建议的研究重点是基因的应用， 和分子工具来操纵H. pylori染色体和DNA的应用 微阵列技术监测宿主和病原体在H.幽门 感染和疾病的动物模型。具体而言，我们建议研究 H.小鼠和长爪沙鼠的幽门螺杆菌感染。虽然没有细胞 我们建议使用的文化模型或动物模型可以充分反映 在人类中看到，小鼠感染模型可以用于有效地 研究H.幽门螺杆菌在胃中定植。我们希望长期遵循 感染小鼠和宿主细胞对长期H.幽门 与未感染相比，通过转录谱变化测量的携带 同窝出生的此外，小鼠感染模型可用于研究一种形式的 H.幽门螺杆菌，MALT淋巴瘤，我们建议研究这一点， 长期的H.小鼠幽门螺杆菌感染的细菌转录 分析和使用小鼠DNA微阵列来跟踪宿主反应 以及恶性转化过程中发生的变化。我们亦建议 鉴定胃定植和持续存在所必需的细菌基因， 用我们实验室开发的一种叫做微阵列的方法 转座子标记（MATT）策略。H.幽门螺杆菌感染反映了一个特别 宿主与病原体相互作用的有趣例子。微生物是一种工具 来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