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-Barre Syndrome. Despite the availability of the entire nucleotide sequence of the C. jejuni genome, remarkably little is known about its mechanisms of pathogenicity. The pathology associated with C. jejuni infections, combined with a variety of observations in experimental animals and tissue culture systems, suggest that disease may be the result of the development of an intimate functional interface between these bacteria and intestinal epithelial cells. As a consequence of these intimate interactions, C. jejuni can gain access to the cells that line the intestinal epithelium and can stimulate the production of pro-inflammatory cytokines. The molecular and cellular bases for these events are poorly understood. The long term goal of this research project is to gain a better understanding of the molecular and cell biology of the interactions of C. jejuni with host cells. We propose to execute the following specific aims: 1) To identify C. jejuni determinants which mediate its interactions with host cells;2) To deepen the understanding of the cell biology of critical events leading to C. jejuni uptake into and survival within intestinal epithelial cells;3) To investigate the C. jejuni metabolic reprogramming that allows its survival within host cells;and 4) To define the proteoglycome of C. jejuni after growth in vitro or within mammalian cells.