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

Mol Microbiol. 1996 May;20(3):497-505. doi: 10.1046/j.1365-2958.1996.5451068.x.


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

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptation, Physiological
  • Bacterial Proteins / genetics
  • Carbon / metabolism*
  • Chromosome Mapping
  • DNA-Binding Proteins*
  • Drug Resistance
  • Hydrogen Peroxide / pharmacology*
  • Mutation
  • Oxidative Stress*
  • Repressor Proteins / metabolism
  • Salmonella typhimurium / drug effects*
  • Salmonella typhimurium / genetics*
  • Salmonella typhimurium / metabolism
  • Sigma Factor / genetics
  • Transcription Factors / metabolism


  • Bacterial Proteins
  • DNA-Binding Proteins
  • Repressor Proteins
  • Sigma Factor
  • Transcription Factors
  • sigma factor KatF protein, Bacteria
  • Carbon
  • Hydrogen Peroxide