Roles for Motility in Helicobactor pylori pathogenesis

运动在幽门螺杆菌发病机制中的作用

• 批准号: 6625659
• 负责人: Karen M Ottemann
• 金额: $ 29.8万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6625659
• 关键词: Helicobacter; bacteria infection mechanism; bacterial proteins; biological signal transduction; cell motility; chemoreceptors; chemotaxis; flagellum; gastrointestinal infection; gene mutation; genetic promoter element; host organism interaction; laboratory mouse; microorganism immunology; protein structure function

The bacterium Helicobacter pylori inhabits the stomachs of a full 3 billion people--half the world's population. Infections with this bacterium cause significant morbidity and mortality around the globe. In the majority of cases, the bacterium establishes chronic infections that lead to diverse outcomes ranging from asymptomatic carriage to ulcer disease to gastric cancer. Conservative estimates suggest that 5 percent 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. The processes used by H. pylori to establish and maintain infection are just beginning to be worked out. One such process is the ability to swim. H. pylori is motile via organelles called flagella, and it must have functional versions of these organelles in order to colonize animal stomachs. In addition, H. pylori does not swim randomly but instead directs its motility in response to environmental cues in a process called chemotaxis. We are interested in understanding how chemotactic motility is used for infection by this bacterium. Towards this we propose three aims: (i) Ascertain at what points during infection chemotactic motility is used by H. pylori. (ii) Determine how H. pylori chemotaxis is directed by pinpointing which of its chemoreceptors are used for mouse stomach colonization, and to what they respond. (iii) Dissect how information is relayed from the chemoreceptors to the flagellar motor during chemotactic signal transduction in H. pylori by analyzing how a family of proteins, the CheVs, function. Chemotaxis is observed in a number of bacterial pathogens but little is known about its role during infection. What we learn from these studies may apply to other bacteria. For example, the Campylobacter group of bacteria are leading causes of food-borne diarrheal disease, and similarly require motility and chemotaxis for infection.

幽门螺杆菌存在于30亿人的胃里，占世界人口的一半。这种细菌的感染在地球仪中引起显著的发病率和死亡率。 在大多数情况下，细菌建立慢性感染，导致从无症状携带到溃疡疾病到胃癌的各种结果。 保守的估计表明，5%的感染者-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.幽门螺杆菌建立和维持感染的机制才刚刚开始研究。 其中一个过程就是游泳的能力。 H.幽门螺旋杆菌通过称为鞭毛的细胞器运动，并且它必须具有这些细胞器的功能版本以便在动物胃中定殖。 此外，H.幽门螺杆菌不是随机游动的，而是在一个称为趋化性的过程中，根据环境线索引导其运动。我们有兴趣了解如何趋化运动是用于感染这种细菌。为此，我们提出了三个目标：（i）确定在感染过程中的哪些点的趋化运动是由H。幽门。(ii)确定H。幽门螺杆菌的趋化性是通过精确定位哪些化学受体用于小鼠胃定殖以及它们对什么反应来指导的。(iii)详细分析了在H. pylori通过分析一个家族的蛋白质，CheV，功能。在许多细菌病原体中观察到趋化性，但对其在感染过程中的作用知之甚少。 我们从这些研究中学到的东西可能适用于其他细菌。 例如，弯曲杆菌属细菌是食源性腹泻病的主要原因，并且同样需要运动性和趋化性来进行感染。