Campylobacter jejuni has become the most frequently identified cause of acute infectious diarrhea in the developed world and is the most commonly reported bacterial cause of foodborne infection in the U.S.(1). Despite its global importance and economic impact, little is known regarding mechanisms of pathogenesis. This is due in large part to the paucity of high resolution experimental systems for studying infection in vivo. We have recently developed murine models that are characterized by the efficient establishment of gastrointestinal infection following oral inoculation, high levels of colonization and long term persistence. We propose to exploit these models to study determinants of pathogenicity, with an emphasis on chemotaxis. We hypothesize that chemotaxis is required for both the establishment and maintenance of infection and this contention is supported by our preliminary data and reports by other investigators. Despite its obvious importance, the chemotactic system of C. jejuni has remained almost entirely uncharacterized. Similarities between the predicted chemotaxis proteins of C. jejuni and H. pylori suggest that our analysis will have broad implications. An understanding of the signal transduction pathways that guide bacterial movement in vivo may have practical applications for the development of antimicrobial therapeutics as well as vaccines. Specifically, we propose to: 1. Characterize the interactions between Campylobacter and the mouse gastrointestinal tract in our murine models of C. jejuni colonization. 2. Characterize the role of chemotaxis genes identified by genome sequence analysis in chemotactic responses measured in vitro and infection measured in vivo. 3. Conduct a biochemical characterization of the central signaling pathway that controls Campylobacter chemotaxis.
| Chang, Christopher; Miller, Jeff F (2006) Campylobacter jejuni colonization of mice with limited enteric flora. Infect Immun 74:5261-71 |
| MacKichan, Joanna K; Gaynor, Erin C; Chang, Christopher et al. (2004) The Campylobacter jejuni dccRS two-component system is required for optimal in vivo colonization but is dispensable for in vitro growth. Mol Microbiol 54:1269-86 |
