DNA recombinational repair in Helicobacter pylori

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Helicobacter pylori infects the stomachs of approximately 50% of humans and results in a series of human gastric diseases. It is highly adapted to maintain persistence in the human gastric mucosa, a niche full of oxidative and acid stress agents that cause bacterial DNA damage. H. pylori exhibits the highest level of genetic diversity known among bacteria, and a major contributor to this diversity is the high frequency of DNA recombination. We hypothesize that the repair of DNA damage by recombination both facilitates H. pylori's genetic diversity and contributes to its in vivo survival. H. pylori likely has a unique mechanism for DNA recombinational repair, particularly for the initial steps including the recognition of damaged DNA and subsequent recruitment of recombination repair proteins. The exploratory goals of this proposal are to define the roles of four putative proteins (RecN, RecJ, RecR, and HP1553) involved in DNA recombinational repair. Gene-targeted mutant strains in these 4 genes will be examined for their sensitivity to DNA damaging agents, for their survival under oxidative and acid stress conditions, and for their DNA recombination frequency. The roles of these genes/proteins in the in vivo survival of H. pylori will be studied using a mouse model of infection. A secondary exploratory goal is to identify additional components of the recombinational repair system in H. pylori by screening for mitomycin C-sensitive strains from a random transposon mutagenesis library. Alternatively, the proteins that interact with RecN, RecB, or RecR will be identified via cross-linking and coimmunoprecipitation approaches. Our studies are designed to shed light on H. pylori genes involved in the bacterium's unique ability to survive the gastric environment, and to provide novel insight into the unique mechanisms of DNA recombinational repair. PUBLIC HEALTH RELEVANCE: Helicobacter pylori persistently infects the human gastric mucosa and causes serious conditions such as peptic ulcer disease and gastric cancers. Studying the DNA recombinational repair system will help us understand how H. pylori can adapt to and persist in the human stomach.