Persistence of Salmonella typhimurium in Swine

S. typhimurium is one of the major causes of salmonellosis in humans. Pigs persistently infected with S. typhimurium are one of the major reservoir of this pathogen. Generally, pigs persistently infected with S. typhimurium are asymptomatic. One means to reduce the risk of food borne infections caused by S.typhimurium is to prevent pigs from becoming persistently infected. This project is designed to understand the mechanisms promoting persistent infections. The initiation of infection requires the attachment of S. typhimurium to the lining of the small intestine. There are two types of cells int he small intestine that are targets for attachment: epithelial cells call enterocytes and epithelial cells call M-cells. Our current hypothesis, which is based on our previous experiments using mutant S.typhimurium that do not attach to enterocytes, is that attachment to enterocytes is important for the development of persistent infectionswhile attachment to M-cells results in disease. The goals of this study are to confirm that our non-adhesive mutants indeed do not attach to enterocytes in pigs but retain the ability to attach to M-cells. Furthermore, we have found that a novel mechanism allows S. typhimurium to sense its location in the intestine and turn on a set of genes that promote its ability to colonize enterocytes and this resultsin persistent infections. We plan to create additional mutants that no longer can control these genes and determine whether the mutants have lost the ability to cause persistent infections.