Effect of repeated in vivo passage (in mice) on Salmonella typhimurium dam mutant virulence and fitness

Numerous studies have shown that Salmonella typhimurium dam mutants are highly attenuated for virulence in mice. In vivo studies have also shown that, on oral and intraperitoneal administration, low number of these mutants is able to colonize and persist in target organs. So, they must sense and overcome a myriad of host killing mechanisms. Our goal was to evaluate the effect of in vivo passage, in mice, on S. typhimurium dam mutant virulence and fitness. Swiss albino mice were used for the determination of LD50 and enumeration of bacteria recovered from liver eight days postinfection. Our results indicate that LD50 values of re-isolated mutants were at least two to three-fold lower than those of control strains. Strains re-isolated from liver showed decreased in vitro sensitivity toward sodium deoxycholate and H(2)O(2) than control strains. In addition, the number of re-isolated mutants colonizing spleen and liver was relatively higher than control strains. According to these results, we suggest that persistence of S. typhimurium dam mutants within target organs can increase their in vivo virulence in mice. (C) 2007 Elsevier Masson SAS. All rights reserved.