Campylobacter jejuni colonization and the resident microbiota

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 DESCRIPTION (provided by applicant): Campylobacter jejuni is the most common cause of food-born diarrhea in the United States. Although it is most often associated with self-limiting diarrheal disease, a small proportion of infected patients develop a more serious neuro-degenerative complication known as Guillain-Barré Syndrome. Despite many important advances in the field, still remarkably little is known about its mechanisms of pathogenicity. C. jejuni has the ability to efficiently colonize the intestine of a broad range of hosts, which allow this pathogen to gain access to the food chain thus presenting major challenges to the food industry. Therefore, the study of C. jejuni colonization offers unique opportunities to gain knowledge about mechanisms by which a pathogen can establish itself in the intestinal track of its hosts and successfully compete with the resident microbiota. Securing nutrients and terminal electron acceptors for their respiratory chain are central to the ability of pathogens to colonize given niche. Although knowledge of microbial metabolism in model organisms is substantial, much less is known about metabolism during infection. The versatility of microbial pathogens to acquire nutrients is emerging as central for their ability to colonize in the face of steep competition from the resident microbiota. Many basic parameters of C. jejuni central metabolism, its ability to utilize nutrients, and several aspects of its diversified respiratory chins have been established. However, these studies have been largely carried out in culture medium and therefore the understanding of C. jejuni metabolism during infection is still limited. We aimed to carry out a comprehensive survey of the C. jejuni metabolic requirements to colonize the gut. In addition, we intend to explore the role of the resident microbiota in the modulation of C. jejuni metabolic requirements. Over the last decade, our laboratory has built considerable expertise in the study of C. jejuni and has made significant contributions to the understanding of its pathogenesis. We plan to leverage this expertise to address what we believe are among the most fundamental questions in C. jejuni biology, namely its metabolic requirements for effective host colonization and its interplay with the resident microbiota.