DEFINING THE ROLE OF SALMONELLA TYPHIMURIUM ARTAB TOXIN IN DIARRHEAL DISEASE TO PROMOTE BOVINE VACCINE DEVELOPMENT

despite the licensure and use of bovine salmonella vaccines, the presence of this bacterial pathogen on large beef and dairy operations remains common. salmonella can be harbored subclinically, but causes significant morbidity and mortality in calves, and reducing or eliminating this pathogen is an economically impactful priority for agriculture. in addition, cows are a significant source of transmission to humans, and concerns over increasingly antibiotic-resistance salmonella has focused attention on the need for improved methods of prevention. an inexpensive, effective and safe vaccine that can induce mucosal responses and protect cows from systemic disease will improve animal welfare and production, and potentially reduce transmission to humans. bacterial ab5 toxins represent essential virulence factors in certain gram negative bacteria and and are important vaccine antigens in licensed vaccines. the proposed studies are based on the identification of a novel ab5 toxin in s. typhimurium dt014, and the hypothesis that this toxin is expressed during clinical infection, a contibuting virulence factor to disease and a potential vaccine antigen. in the proposed studies we will; 1) determine the expression of artab in clinical disease, 2) define a role for artab in cellular cytotoxicity and barrier dysfunction and 3) quantify the effects of toxin deletion on pathogenicity. these studies are the first that will define contributions of artab to toxicity and virulence, and represent primary steps to the long-term goal of developing a mucosal salmonella vaccine for use in cows. this project aligns with the priority of disease prevention and control within the usda-afri animal health and disease program area.