Helicobacter Host Interactions in Animal Models

描述(申请人提供)：幽门螺杆菌感染是因 与胃炎和消化性溃疡有关，以及两种胃病 恶性肿瘤、胃癌与B细胞黏膜相关淋巴组织 (MALT)淋巴瘤。我们提出的研究重点是遗传基因的应用 以及操纵幽门螺杆菌染色体和使用DNA的分子工具 同时监测幽门螺杆菌宿主和病原体的微阵列技术 感染和疾病的动物模型。具体来说，我们建议研究 幽门螺杆菌感染对小鼠和蒙古沙土鼠的影响。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 在人类身上看到的小鼠感染模型可以有效地用于 研究幽门螺杆菌是如何在胃中定植的。我们希望跟踪小鼠的长期感染和宿主细胞对长期幽门螺杆菌的反应 通过转录图谱的变化来衡量与未感染相比的携带量 一窝产仔。此外，小鼠感染模型也有助于研究一种形式的 幽门螺杆菌、MALT淋巴瘤引起的恶性肿瘤，我们建议通过细菌转录来研究幽门螺杆菌长期感染小鼠的这一特征 通过使用小鼠DNA微阵列来跟踪宿主反应 以及在恶变过程中发生的变化。我们还建议 确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名为微阵列的方法进行胃 转座子标记(MAT)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耐人寻味的例子。微生物充当了一种工具 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了解细菌的本质 致病性。

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.