Grant: Operating Grant

Salmonella species continue to cause much morbidity and mortality worldwide, causing human diseases ranging from gastroenteritis to typhoid fever. In addition, there is an ever-increasing incidence of antibiotic resistant Salmonella worldwide, especially in non-typhoidal Salmonella. This application proposes to continue our work on Salmonella pathogenesis by applying a systematic approach to study how its secreted virulence factors work. This will include several systems biology approaches (proteomics, metabolomics, proteolysis), as well as examining the function of several virulence factors in concert, focusing on host immune and metabolic pathways. In addition, we will further define the function of these factors on pathogenesis in relevant tissues in murine models of typhoid fever, gastroenteritis, and long-term carriage. Collectively this information will yield new information about Salmonella as an enteric pathogen, infectious disease mechanisms, and explore the interactions that occur between bacterial virulence factors and host defense mechanisms. It is hoped that by understanding the basic mechanisms of disease, potential lines of therapeutics can be developed.