Virulence of non-type 1-fimbriated and nonfimbriated nonflagellated Salmonella typhimurium mutants in murine typhoid fever.

The virulence of Salmonella typhimurium mutants that were unable to synthesize type 1 fimbriae was tested in a murine typhoid fever model. Nonfimbriated mutants (fim) exhibited a lower 50% lethal dose than a wild-type (fim+) strain and produced significantly higher mortality (fim, 55%; fim+, 37% [P less than 0.002]) in mice that were challenged orally. There was no difference in virulence when the wild-type and mutant strains were injected intraperitoneally into mice. The progress of a short-term lethal infection was monitored after oral inoculation of mice with a mixture containing equivalent numbers of fim+ wild-type and fim mutant bacteria. The results indicated that while both strains colonized the intestinal tract equally well and invaded internal organs, the S. typhimurium fim mutant proliferated in the blood of the mice faster than the fim+ strain. The results of the mixed oral challenge suggested that bacteremia caused by fim+ S. typhimurium was reduced or delayed by the sequestration of the fimbriated bacteria in the spleen, liver, and kidneys. Thus, type 1 fimbriae were not virulence factors for S. typhimurium in this model, and the fimbriae may be an impediment to the pathogen in this setting. An S. typhimurium double mutant lacking type 1 fimbriae and flagella (fla) also was tested in mice. The virulence of the fim fla mutant was greatly reduced compared with that of the wild-type strain (mortality from fim fla challenge, 11% [P less than 0.0005]). The significance of this latter result is discussed in relation to host adaptation by pathogenic salmonellae.