Roles for motility in Helicobacter pylori pathogenesis

描述（由申请人提供）：幽门螺杆菌是一种人类胃病原体，感染世界上大约一半的人口，引起从无症状胃炎到胃溃疡再到胃癌的疾病。保守的估计表明，感染者中有5%--1.5亿人--发展成某种形式的疾病。H.幽门螺杆菌是世界卫生组织的国际癌症研究机构列为第一类致癌物的唯一细菌，这一点令人怀疑。这种细菌的感染是几种类型胃癌的危险因素，包括胃腺癌和粘膜相关淋巴组织（MALT）淋巴瘤。H.幽门螺杆菌具有几种能力，有助于其定植并引起疾病。这些能力之一是定向运动，或趋化性。趋化性是生物体感知环境并做出反应的能力。我们发现趋化性有助于H.幽门感染特别是，我们发现趋化性有助于H。幽门螺杆菌最初建立感染，维持慢性感染，定植在胃的所有区域，并引起疾病的第一步，炎症。我们有兴趣更好地了解趋化性如何帮助H。幽门感染。为了实现这一目标，我们提出了三个目标：（1）确定趋化性如何促进胃窦的定植以及趋化性如何触发炎症;幽门螺杆菌利用趋化性向一种关键的营养物质铁移动;（3）剖析信息是如何从感受环境的化学感受器传递到趋化性信号转导级联。特别是，确定CheZ和三个CheV的角色。微生物对抗生素的抵抗力越来越强，因此我们需要更清楚地了解感染机制。因此，这些实验可以帮助我们确定关键的抗生素或疫苗靶点。概述：幽门螺杆菌是一种感染人类胃的微生物，感染了世界上大约一半的人口，引起的疾病包括无症状胃炎、胃溃疡和胃癌。细菌的一种特性有助于H。幽门螺杆菌在胃中生存的能力是游泳。我们的工作旨在确定H。幽门螺旋杆菌游动促进疾病并帮助细菌寻找营养。此外，我们将剖析这一过程的分子细节，长期目标是鉴定出能够成为良好抗菌靶标的蛋白质。

DESCRIPTION (provided by applicant): Helicobacter pylori is a human gastric pathogen that infects approximately half of the world's population, causing diseases that range from asymptomatic gastritis to gastric ulcers to gastric cancers. Conservative estimates suggest that 5% of those infected-150 million people-develop some form of disease. H. pylori has the dubious distinction of being the only bacterium classified as a Group I carcinogen by the International Agency for Research on Cancer of the World Health Organization. Infection by this bacterium is a risk factor for several types of gastric cancer including gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. H. pylori possesses several abilities that help it colonize and cause disease. One of these abilities is directed motility, or chemotaxis. Chemotaxis is the ability of an organism to sense its environment and move in response. We have found that chemotaxis aids H. pylori infection. In particular, we have found that chemotaxis helps the H. pylori establish infection initially, maintain a chronic infection, colonize all regions of the stomach and cause the first step of disease, inflammation. We are interested in a better understanding of how chemotaxis helps H. pylori infect. Toward this goal we propose three aims: (1) Determine how chemotaxis promotes colonization of the stomach antrum and how chemotaxis triggers inflammation; (2) Ascertain how H. pylori uses chemotaxis to move towards a critical nutrient, iron; (3) Dissect how information is relayed from the chemoreceptors, which sense the environment, to the chemotaxis signal transduction cascade. In particular, determine the roles of CheZ and the three CheVs. Microbes increasingly resist antibiotics, so we need a clearer comprehension of infectious mechanisms. Thus these experiments may help us pinpoint key antibiotic or vaccine targets. Lay Summary: Helicobacter pylori is a human stomach-infecting microbe that infects approximately half of the world's population, causing diseases that range from asymptomatic gastritis to gastric ulcers to gastric cancers. One bacterial property that helps H. pylori survive in the stomach is the ability to swim. Our work aims to determine how H. pylori swimming promotes disease and helps the bacterium find nutrients. Additionally, we will dissect the molecular details of this process, with the long-term goal of identifying proteins that would make good antibacterial targets.