Degree Type

Dissertation

Date of Award

2017

Degree Name

Doctor of Philosophy

Department

Veterinary Microbiology and Preventive Medicine

Major

Biomedical Sciences

First Advisor

Steve A. Carlson

Abstract

Saccharomyces cerevisiae fermentation metabolites have been used for over a century as feed additives to improve the feed efficiency of food-producing animals. During the routine microbiological monitoring of poultry houses, reports emerged indicating a significant decrease in Salmonella recovered from houses that recently contained broilers fed a yeast fermentation metabolite product (XPCTM) when compared to houses that recently harbored birds fed a conventional diet. Preliminary studies evaluated the scope and breadth of this discovery, as well as the underlying mechanisms. Based on these studies, we developed the hypothesis (central to this dissertation) that XPC has anti-Salmonella properties stemming from the immunomodulation of the mucosal immune system, possibly at the bridge between the adaptive and innate immune systems. Addressing this hypothesis involved field studies evaluating the anti-Salmonella effects of XPC in cattle and poultry naturally infected with the pathogen. Additional studies investigated the same parameters in experimentally infected animals. These studies revealed that supplementing animals with XPC resulted in a significant reduction in the shedding and colonization of Salmonella, a reduction of integron- and plasmid- associated antibiotic resistance in input and naturally occurring Salmonella isolates, and the attenuation of pathogenicity of isolates obtained in both the field and laboratory settings. Further studies explored the potential mechanism underlying the immunomodulatory effects of XPC after pilot studies revealed that leukocytes recovered from XPC-treated animals demonstrated an enhanced phagocytic clearance of Salmonella. Additionally, gene expression studies revealed that this clearance phenomenon may be linked to enhanced local complement C3 expression observed in XPC-fed birds. Enhanced C3 production will lead to elevated production of complement C5, whose cognate receptor is a druggable G-protein coupled receptor C5aR1 that plays a central role in enhancing the phagocytic capabilities of innate effector cells. Thus, a series of in vivo experiments were conducted in order to ascertain the specific role that XPC plays in the improvement of innate immune activity via C5aR1. Resulting evidence suggests that C5aR1 may play a novel role in the immunostimulatory efficacy of XPC, which enhances the clearance of Salmonella. Therefore, this thesis provides evidence supporting the anti-Salmonella and immunostimulatory effects of XPC.

Copyright Owner

Kristina Marie Feye

Language

en

File Format

application/pdf

File Size

133 pages

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