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. typhimuriumrpoSstiAstiB, 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 μM 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 rpoSstiA, 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 μM H2O2 exposure, but only stiA was regulated (repressed) by (reduced form) OxyR.