Date of Award

12-2017

Degree Type

Thesis

Degree Name

Master of Science

Major

Microbiology

Major Professor

Jeremiah G. Johnson

Committee Members

Sarah L. Lebeis, Todd B. Reynolds

Abstract

Campylobacter jejuni is a leading cause of bacterial-derived gastroenteritis worldwide. In the developed world, campylobacteriosis is most commonly acquired following the consumption of cross contaminated foods or undercooked poultry meat, since the bacterium asymptomatically colonizes chickens. In the developing world, infection most commonly occurs through drinking contaminated water. Following ingestion, Campylobacter adheres to the intestinal epithelium and mucus layer, causing toxin-mediated inflammation and inhibition of fluid reabsorption. Currently, the bacterial mechanisms behind colonization and disease are relatively unknown. Thus, it is important to identify factors that influence the development of these sequelae during and after initial C. jejuni infection.Ferrets (Mustela putorius furo) have been previously used as an animal model of human campylobacteriosis, but intensive investigation into this model has yet to be performed. Thus, in this study, we non-invasively examined for disease in ferrets and determined whether there were any effects on development following infection with C. jejuni. Ferrets were effectively colonized by C. jejuni with peak fecal loads observed at day 3 post-infection, and with full resolution by day 12 post-infection. Infected male ferrets had reduced weight when compared to uninfected males early in infection, but this was resolved by the conclusion of the experiment. All infected ferrets exhibited reduced activity and minor changes in fecal consistency. Cytokine levels in serum increased in response to infection, with significance observed for IL-10 and TNF (tumor necrosis factor alpha). Occult blood was observed in both uninfected and infected cohorts. Additionally, in response to infection, the neutrophil protein calgranulin C (S100A12) was found to be increased in the feces of both ferrets and humans infected with C. jejuni, while calprotectin (another neutrophil protein) was not. The addition of either purified S100A12 or of calprotectin to in vitro cultures of C. jejuni was found to inhibit growth in a zinc-dependent manner. These results suggest that upon infection with C. jejuni, neutrophils that are trafficked to the intestine release S100A12 and possibly calprotectin as a mechanism for inhibiting C. jejuni growth in the intestine.

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