Analysis of molecular mechanisms underlying systemic salmonellosis using One Health models

Salmonella is a bacterial pathogen of global importance. Some types of Salmonella are specific to humans and cause typhoid, a severe systemic disease (e.g. S. Typhi). A capsule comprised of sugars on the surface of S. Typhi is believed to help it evade the immune system, but this is challenging to study in people. The same capsule (called the Vi antigen encoded by via genes) is present in some strains of Salmonella Dublin, which cause typhoid-like disease in cattle. This offers a tractable model to understand the role it plays during infection. My research will involve creating mutations within the via genes of S. Dublin and testing how these affect interactions with immune system components in the laboratory (e.g. blood cells and serum components that kill bacteria). I will then use surgical models to study how Vi helps S. Dublin to spread from the gut to other organs and produce disease in cattle. The role of Vi has mostly been researched using mouse models and strains that naturally lack via genes but have been engineered to express them. The presence of Vi in S. Dublin offers a rare opportunity to study the role of Vi in a natural microbe-host combination.