The invasive disease caused by Salmonella typhimurium in mice resemble
s the acute phase of human typhoid fever caused by Salmonella typhi, a
nd experimental murine salmonellosis is a widely used experimental mod
el for systemic salmonellosis. In this paper we demonstrate that murin
e S. typhimurium infection can also be used to model the development o
f the chronic carrier state that develops in humans after infection wi
th S. typhi. We describe a virulent variant of S. typhimurium that has
decreased expression of AgfA fibers under all environmental condition
s studied and that causes a chronic carrier state in BALB/c mice after
peroral inoculation. The chronic carrier state is associated with per
sistence of bacteria in the small intestine, spleen, and liver, and ch
ronic infection continues despite the development of protective immuni
ty to challenge with virulent Salmonella.