Influence of an E. coli hyperadherent probiotic on Salmonella intestinal colonization

Project Abstract Salmonellosis continues to be one of the most important causes of food-borne illness in the U.S. Furthermore, multiple-antibiotic resistant Salmonella strains are becoming untreatable infectious diseases. Poultry meat and eggs are major sources of Salmonella food-borne illness, due to carriage of these bacterial pathogens in the intestinal microbiome. The NIH goal to reduce Salmonella human infections is directly linked to the USDA goal of reducing carriage of Salmonella in poultry. While these goals have been high priorities for many years, current control efforts have been uniformly unsuccessful. Accordingly, new approaches are needed to address this infectious disease problem in the United States. The long-term goal of our work is to reduce or eliminate carriage of Salmonella in poultry flocks. The working hypothesis of this proposal is that an engineered probiotic strain that expresses a key Salmonella adherence factor, type 1 fimbriae, can outcompete pathogenic Salmonella strains for position in the intestinal microbiome of poultry. Significant reduction of Salmonella carriage in poultry will significantly improve the food safety of poultry and will decrease the incidence of salmonellosis. There are two specific aims in this proposal: 1) To optimize the binding activity of the type 1 FimH gene expressed in E. coli Nissle 1917, 2) Demonstrate that the hyper adherent E. coli strain can competitively exclude Salmonella strains from colonizing the intestinal epithelium of the poultry host. At the completion of this project, we expect to have demonstrate that an engineered E. coli probiotic strain can significantly reduce intestinal carriage of Salmonella in chickens. The focus of this project is to provide an avenue to reduce cases of human salmonellosis and reduce the human infection risks posed by multiple-antibiotic resistant Gram-negative bacteria.