POSITIVE CONTROL OF A REGULON FOR DEFENSES AGAINST OXIDATIVE STRESS AND SOME HEAT-SHOCK PROTEINS IN SALMONELLA-TYPHIMURIUM

S. typhimurium become resistant to killing by H2O2 and other oxidants when pretreated with nonlethal levels of H2O2. During adaptation to H2O2, 30 proteins are induced. Nine are constitutively overexpressed in dominant H2O2-resistant oxyR mutants. Mutant oxyR1 is resistant to a variety of oxidizing agents and overexpresses at least 5 enzyme activities involved in defenses against oxidative damage. Deletions of oxyR are recessive and uninducible by H2O2 for the 9 proteins overexpressed in oxyR1, demonstrating that oxyR is a positive regulatory element. The oxyR1 mutant is also more resistant than the wild-type parent to killing by heat, and it constitutively overexpresses 3 heat-shock proteins. The oxyR regulatory network is a previously uncharacterized global regulatory system in enteric bacteria.