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- ELUCIDATING THE POTENTIAL ROLE OF ARYL HYDROCARBON RECEPTOR IN THE PATHOGENESIS OF CAMPYLOBACTER JEJUNI.
- Ahmed, Husnain
- Electronic Theses & Dissertations
Campylobacter jejuni is a leading cause of human foodborne gastroenteritis in the US, with an incidence rate of 13.6 diagnosed cases per 100,000 individuals. The most frequent cause of C. jejuni infection in the US is the consumption of chicken contaminated during processing. Macrolide antibiotics such as azithromycin and ciprofloxacin are the drug of choice to treat C. jejuni infection in human populations. However, the over-use of antibiotics has led to the emergence of antimicrobial...
Show moreCampylobacter jejuni is a leading cause of human foodborne gastroenteritis in the US, with an incidence rate of 13.6 diagnosed cases per 100,000 individuals. The most frequent cause of C. jejuni infection in the US is the consumption of chicken contaminated during processing. Macrolide antibiotics such as azithromycin and ciprofloxacin are the drug of choice to treat C. jejuni infection in human populations. However, the over-use of antibiotics has led to the emergence of antimicrobial-resistant C. jejuni strains and reduced treatment efficacy. The development of antimicrobial resistance traits in C. jejuni isolates has augmented the need to develop innovative strategies to treat drug-resistant C. jejuni infections in human and animal populations.Members of the genus Lactobacillus are commonly used as probiotics, however the mechanisms by which they provide protective health effects remain elusive. In the first study, we described a novel mechanism by which L. murinus attenuates pro-inflammatory responses in the human intestinal epithelial cells. The results showed that L. murinus activates aryl hydrocarbon receptor (AHR) to decrease the secretion of IL-8 in response to exogenous stimulation by TNF-alpha in the human intestinal epithelial cells. Furthermore, activating the AHR with its defined ligand also reduced the secretion of IL-8 upon TNF-alpha stimulation. These results suggest that AHR can a novel target for inflammatory bowel disease (IBD) treatment. Furthermore, these results suggest that L. murinus can be a novel probiotic for treating IBD. In the 2nd study, we determined the effect of prophylactic inoculation of L. muirnus on the pathogenesis of C. jejuni in the BALB/c IL-10-/- mice. A total of 41 BALB/c IL-10-/- mice were used in this study. 11 mice were sham inoculated, 10 mice received only L. murinus, 10 mice received only C. jejuni, and 10 mice in the test group received both L. murinus and C. jejuni such that L. murinus was inoculated 32 days before C. jejuni infection. In addition, 30 days post-C. jejuni challenge mice were sacrificed and assessed for gut pathology. Fecal samples were also collected to access bacterial colonization levels in the gut through routine culture techniques and 16S sequence analysis. Both positive control group for C. jejuni and test groups mice developed severe colitis. 16S analysis of fecal DNA revealed that bacterial diversity in the test and positive control group for C. jejuni was significantly less (P<0.001) than in the Lactobacillus only and negative control group. These results suggest that prophylactic administration of L. murinus does not protect BALB/c IL-10-/- mice from developing disease following C. jejuni infection. Overall, this dissertation contains identification of a novel mechanism of action of L. murinus. The results provide insights for the identification of novel targets to treat C. jejuni disease without using antibiotics. This dissertation provides a basis for the future studies to further dissect the role of the AHR in the pathogenesis of C. jejuni.