Identification of a Novel Virulence Factor in Campylobacter jejuni: Characterization, Pathogenesis and Immunity of Cj1534c
Committee ChairJoens, Lynn A.
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PublisherThe University of Arizona.
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AbstractInfection with Campylobacter jejuni is one of the leading causes of bacterial gastroenteritis, causing an estimated 2.1 million cases annually. Although infections with C. jejuni resolve naturally, over 13,000 hospitalizations and 100 deaths are attributed to this organism. Despite these alarming numbers, relatively little is known about C. jejuni pathogenesis, when compared to other enteric pathogens. This dissertation outlines the identification and characterization of a novel virulence factor in C. jejuni, the protein expressed by the Cj1534c gene. Using microarray and RT real time PCR, Cj1534c was found to be greater than 10 fold over expressed in both swine and poultry. Employing immunoelectron microscopy, we determined that at least a subset of the protein is surface localized. Based on the surface localization and up regulation in poultry, colonization studies were performed. Results demonstrate a significant reduction in colonization by a Cj1534c deficient mutant as compared to wild type. In vitro binding assays using both biotic and abiotic surfaces indicate this protein is involved with attachment to surfaces, as well as the invasion of cultured epithelial cells. In vitro findings were confirmed in vivo using swine, with the Cj1534c mutant being highly attenuated as compared to wild type strains. Additionally, the Cj1534c protein was tested for its potential as a vaccine in poultry. Studies demonstrated that Cj1534c recombinantly expressed in a Salmonella expression vector partially protected chickens, reducing cecal colonization three logs as compared to wild type. Taken together, this data demonstrates a major role of Cj1534c in both chicken cecal colonization and infection of swine.