Roles for motility in Helicobacter pylori pathogenesis

点击翻译按钮获取中文摘要

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.