GENETICS AND CELLULAR BASIS OF H PYLORI PATHOGENESIS

幽门螺杆菌感染了世界上近一半的人口， 特别是在胃癌发病率与之相当的发展中国家， 在一些国家，这是导致恶性肿瘤和消化性溃疡的主要原因。 重要的流行病学和生物学证据表明，H. 幽门螺杆菌感染是胃病发生发展的必要危险因素 癌症和消化性溃疡。人们对细菌因素知之甚少 允许幽门螺杆菌感染胃组织或那些 导致伴随而来的慢性、持续性炎症状态 感染和胃病。此外，宿主细胞对H. 幽门螺杆菌感染的定义尚未确定。我们提出了两个广泛的具体目标 为了阐明病原体和细菌之间相互作用的本质。 宿主：1)确定幽门螺杆菌毒力因子对 与宿主细胞相互作用的分子和细胞生物学；以及2) 定义与之相关的宿主细胞的生物学后果 幽门螺杆菌对细胞的附着和随后的稳定感染 目标。我们将利用视频和共聚焦显微镜的独特方法 研究宿主细胞在细胞内的转运和对 感染，我们将利用新的分子方法来识别新的 受环境调控并在体内表达的细菌基因。 此外，我们建议使用一种名为 差异显示法研究活菌和细菌的作用效果 影响真核细胞的因素。我们实验室以前对H. 幽门螺杆菌和其他利用这些方法的肠道病原体 提供了相关经验，并产生了令人兴奋的见解 寄主-病原体相互作用的生物学后果。因此，我们 希望有类似的方法来理解糖尿病的发病机制 幽门螺杆菌感染将是卓有成效的。

Helicobacter pylori infects nearly half of the world's population, especially in developing countries paralleled by rates of gastric cancers, a leading cause of malignancy in some countries, and peptic ulcer disease. Significant epidemiological and biological evidence suggests that H. pylori infection is a necessary risk factor for the development of gastric cancer and peptic ulcers. Little is known about the bacterial factors that permit H. pylori to infect gastric tissue or those gene products that bring about the state of chronic, persistent inflammation that accompanies infection and gastric diseases. As well, the response of host cells to H. pylori infection has not been defined. We propose two broad specific aims to elucidate the nature of the interaction between the pathogen and the host: 1) to define the contribution of H. pylori virulence factors to the molecular and cell biology of the interaction with host cells; and 2) to define the biological consequences to the host cell associated with the attachment and subsequent stable infection by H. pylori to cellular targets. We will utilize unique methods of video and confocal microscopy to study Intracellular trafficking and response of host cells to Infection, and we will exploit novel molecular methods to identify new bacterial genes that are environmentally regulated and expressed in vivo. In addition, we propose to utilize a molecular method known as differential display to study the effect of viable bacteria and bacterial factors on eukaryotic cells. Previous studies in our laboratories on H. pylori and other enteric pathogens utilizing these approaches have provided the relevant experience and have produced exciting insights into the biological consequences of the host-pathogen interaction. Thus, we expect that a similar approach to understand the pathogenesis of Helicobacter infection will be fruitful.