Karen M. Ottemann, Ph.D.
University of California at Santa Cruz

Helicobacter pylori: Proteins and Processes that Contribute to Persistent Infection.

Bacterial pathogens that chronically infect humans cause a variety of illnesses such as tuberculosis, stomach ulcers, and leprosy. For example, one such bacterium, Helicobacter pylori, sustains infections for many years, an ability that can result in gastritis, gastric and duodenal ulcers, and/or stomach cancer. Little is known of the H. pylori factors that allow this bacterium to survive in the human stomach for such long periods. Studies of persistence have been hindered by a lack of ways to follow H. pylori infection in animal models without sacrificing the individual being studied. Because of this, long term studies are population-based and require many animals.

We are interested in the processes and proteins that promote persistent infection. Towards the identification of these, we propose to develop techniques to non-invasively monitor H. pylori infection in a mouse. We will then utilize these detection systems to ascertain the dynamics of wild-type H. pylori infection and compare this to mutants that are lacking a factor that may be needed for persistence, motility. Finally, we propose experiments to identify H. pylori genes that are induced only after the bacteria have initiated infection. These genes are likely to be needed for the chronic infection exhibited by H. pylori.

Together, these three components will provide us the tools to study long-term infection, information about how motility aids persistent infection, and the identity of gene products that contribute to stable infection by this world-wide pathogen. Because chronic infections are the therapeutic target for H. pylori, it is crucial that we identify bacterial processes used to sustain infection to facilitate development of novel antimicrobial therapies.

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