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 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.
Seymour
R L
RL
Department of Biomedical Sciences, University of South Alabama, Mobile 36688-0002, USA.
Mishra
P V
PV
Khan
M A
MA
Spector
M P
MP
D000222:Adaptation, Physiological; D001426:Bacterial Proteins / Q000235:genetics; D002244:Carbon / Q000378:metabolism*; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins; D004351:Drug Resistance; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009154:Mutation; D018384:Oxidative Stress; D012097:Repressor Proteins / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D012808:Sigma Factor / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D012808:Sigma Factor; D014157:Transcription Factors; C069567:sigma factor KatF protein, Bacteria; D002244:Carbon; D006861:Hydrogen Peroxide