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: 6943805
• 负责人: Karen M Ottemann
• 金额: $ 4.77万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6943805
• 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.

幽门螺杆菌栖息在整整 30 亿人的胃里——占世界人口的一半。这种细菌的感染在全球范围内导致显着的发病率和死亡率。 在大多数情况下，这种细菌会造成慢性感染，导致多种结果，从无症状携带到溃疡病再到胃癌。 保守估计表明，1.5 亿感染者中，有 5% 会患上某种疾病。幽门螺杆菌是唯一被世界卫生组织国际癌症研究机构列为第一类致癌物的细菌，这一点值得怀疑。这种细菌的感染是多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。幽门螺杆菌用于建立和维持感染的过程才刚刚开始研究出来。 其中一个过程就是游泳的能力。 幽门螺杆菌通过称为鞭毛的细胞器进行运动，并且它必须具有这些细胞器的功能版本才能在动物胃中定殖。 此外，幽门螺杆菌不会随机游动，而是在称为趋化性的过程中根据环境线索引导其运动。我们有兴趣了解趋化运动如何用于这种细菌的感染。为此，我们提出三个目标：（i）确定幽门螺杆菌在感染过程中的哪些点使用趋化性。 (ii) 通过查明幽门螺杆菌的哪些化学感受器用于小鼠胃定植以及它们的反应来确定幽门螺杆菌趋化性是如何定向的。 (iii) 通过分析蛋白质家族 CheV 的功能，剖析幽门螺杆菌趋化信号转导过程中信息如何从化学感受器传递到鞭毛运动。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知识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。