Abstract: Differential Regulation of the ArsRS Regulon in Helicobacter pylori

Nearly 50% of the world’s population is infected by the gastric bacterium Helicobacter pylori. H. pylori infection is one of the major causes of peptic ulcer disease as well as some forms of stomach cancer. H. pylori utilizes a variety of molecular mechanisms to sense and respond to changes in the gastric environment. One such system is called the two-component signal transduction system. H. pylori has three of these systems, but the most well studied is the ArsRS system involved in the bacterial response to changing levels of acidity in the stomach. The ArsRS system regulates the expression of many genes including those important in facilitating successful infection and colonization of a human host. In the clinical setting, many different strains of H. pylori exist, some of which are capable of causing severe human disease while others are not. The goal of this project is to explore the differential activity of ArsRS in regulating genes important in H. pylori virulence across several strains. Techniques of quantitative real-time PCR will be used to measure gene expression and an assay to asses virulence will be developed. Understanding how and to what extent ArsRS impacts the expression of virulence genes in different strains will provide insight into why different H. pylori strains differ vastly in clinical outcomes. H. pylori represents a large disease burden and is currently treatable with antibiotics, although the emergence of resistant strains is possible. This research may lead to the identification of new drug targets useful in treating H. pylori infection.