Roles for Motility in Helicobactor pylori pathogenesis

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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.