The SrrAB two-component regulatory system (TCRS) positively influences the transcription of genes involved in aerobic respiration in response to changes in respiratory flux. Hydrogen peroxide (H2 O2 ) can arise as a byproduct of spontaneous interactions between dioxygen and components of respiratory pathways. H2 O2 damages cellular factors including protein associated iron-sulfur cluster prosthetic groups. We found that a Staphylococcus aureus strain lacking the SrrAB two-component regulatory system (TCRS) is sensitive to H2 O2 intoxication. We tested the hypothesis that SrrAB manages the mutually inclusive expression of genes required for aerobic respiration and H2 O2 resistance. Consistent with our hypothesis, a AΔsrrAB strain had decreased transcription of genes encoding for H2 O2 resistance factors (kat, ahpC, dps). SrrAB was not required for the inducing the transcription of these genes in cells challenged with H2 O2 . Purified SrrA bound to the promoter region for dps suggesting that SrrA directly influences dps transcription. The H2 O2 sensitivity of the AΔsrrAB strain was alleviated by iron chelation or deletion of the gene encoding for the peroxide regulon repressor (PerR). The positive influence of SrrAB upon H2 O2 metabolism bestowed protection upon the solvent accessible iron-sulfur (FeS) cluster of aconitase from H2 O2 poisoning. SrrAB also positively influenced transcription of scdA (ytfE), which encodes for a FeS cluster repair protein. Finally, we found that SrrAB positively influences H2 O2 resistance only during periods of high dioxygen-dependent respiratory activity. SrrAB did not influence H2 O2 resistance when cellular respiration was diminished as a result of decreased dioxygen availability, and negatively influenced it in the absence of respiration (fermentative growth). We propose a model whereby SrrAB-dependent regulatory patterns facilitate the adaptation of cells to changes in dioxygen concentrations, and thereby aids in the prevention of H2 O2 intoxication during respiratory growth upon dixoygen.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)