Roles for Motility in Helicobactor pylori pathogenesis

幽门螺杆菌生活在30亿人的胃里，占世界人口的一半。感染这种细菌会在全球范围内造成严重的发病率和死亡率。在大多数情况下，这种细菌会建立慢性感染，导致从无症状携带到溃疡疾病再到胃癌的各种结果。保守的估计表明，在这些感染者中，有5%--1.5亿人--会患上某种疾病。幽门螺杆菌是唯一一种被世界卫生组织国际癌症研究机构列为I类致癌物质的细菌，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。幽门螺杆菌用来建立和维持感染的过程才刚刚开始研究。其中一个过程就是游泳的能力。幽门螺杆菌通过被称为鞭毛的细胞器移动，它必须具有这些细胞器的功能版本才能在动物胃中定植。此外，幽门螺杆菌并不是随机游泳，而是在一个称为趋化性的过程中，根据环境提示引导自己的运动性。我们有兴趣了解趋化运动是如何被这种细菌感染的。为此，我们提出了三个目标：(I)确定幽门螺杆菌在感染过程中的哪些点使用趋化运动。(Ii)通过确定幽门螺杆菌的哪些化学感受器用于小鼠的胃定植以及它们的反应来确定幽门螺杆菌的趋化作用是如何进行的。(Iii)通过分析一系列蛋白质CheV的功能，剖析在Hp的趋化信号转导过程中，信息是如何从化学感受器传递到鞭毛马达的。在许多细菌病原体中观察到趋化作用，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也适用于其他细菌。例如，弯曲杆菌群是食源性腹泻疾病的主要原因，同样需要运动性和趋化性才能感染。

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.