Essential roles of core starvation-stress response loci in carbon-starvation-inducible cross-resistance and hydrogen peroxide-inducible adaptive resistance to oxidative challenge in Salmonella typhimurium

The starvation-stress response (SSR) of Salmonella typhimurium encompasses the physiological changes that occur upon starvation for an essential nutrient, e.g, C-source, A subset of SSR genes, known as core SSR genes, are required for the long-term starvation survival of the bacteria, Four core SSR loci have been identified in S, typhimurium: rpoS, stiA, stiB, and stiC, Here we report that in S, typhimurium C-starvation induced a greater and more sustainable cross-resistance to oxidative challenge (15 mM hydrogen peroxide (H2O2) for 40 min) than either N- or P-starvation, Of the four core SSR loci, only rpoS and stiC mutants exhibited a defective C-starvation-inducible cross-resistance to H2O2 challenge, Interestingly, (unadapted) log-phase S. typhimurium rpoS and stiA mutants were very sensitive to oxidative challenge, Based on this, we determined if these core SSR loci were important for H2O2 resistance developed during a 60 min adaptive exposure to 60 mu M H2O2 (adapted cells), Both unadapted and adapted rpoS and stiA mutants were hypersensitive to a H2O2 challenge, in addition, a stiB mutant exhibited normal adaptive resistance for the first 20 mins of H2O2 challenge but then rapidly lost viability, declining to a level of about 1.5% of the wild-type strain, The results of these experiments indicate that: (i) the rpoS and stiC loci are essential for the development of C-starvation-inducible cross-resistance to oxidative challenge, and (ii) the rpoS, stiA, and, in a delayed effect, stiB loci are needed for H2O2-inducible adaptive resistance to oxidative challenge, Moreover, we found that both stiA and stiB are induced by a 60 mu M H2O2 exposure, but only stiA was regulated (repressed) by (reduced form) OxyR.