L Bacterial Strains Strain Relevant characteristics Reference 14028 s Wild - type 12 CLIO

Pathogenic microorganisms possess antioxidant defense mechanisms for protection from reactive oxygen metabolites such as hydrogen peroxide (H202), which are generated during the respiratory burst of phagocytic cells. These defense mechanisms include enzymes such as catalase, which detoxify reactive oxygen species, and DNA repair systems which repair damage resulting from oxidative stress. To determine the relative importance of these two potentially protective defense mechanisms against oxidative stress encountered by Salmonella during infection of the host, a Salmonella typhimurium double mutant unable to produce either the HPI or HPII catalase was constructed, and compared with an isogenic recA mutant deficient in DNA repair. The recA mutant was hypersusceptible to H202 at low cell densities in vitro, while the catalase mutant was more susceptible to high H202 concentrations at high cell densities. The catalase mutant was found to be resistant to macrophages and retained full murine virulence, in contrast to the recA mutant which previously was shown to be macrophagesensitive and attenuated in mice. These observations suggest that Salmonella is subjected to low concentrations of H202 while at relatively low cell density during infection, conditions requiring an intact DNA repair system but not functional catalase activity. (J. Clin. Invest. 1995. 95:1047-1053.)