Development of a murine model of chronic Salmonella infection

The invasive disease caused by Salmonella typhimurium in mice resembles the acute phase of human typhoid fever caused by Salmonella typhi, and experimental murine salmonellosis is a widely used experimental model for systemic salmonellosis. In this paper we demonstrate that murine S. typhimurium infection can also be used to model the development of the chronic carrier state that develops in humans after infection with S. typhi. We describe a virulent variant of S. typhimurium that has decreased expression of AgfA fibers under all environmental conditions studied and that causes a chronic carrier state in BALB/c mice after peroral inoculation. The chronic carrier state is associated with persistence of bacteria in the small intestine, spleen, and liver, and chronic infection continues despite the development of protective immunity to challenge with virulent Salmonella.