Open AccessThe Staphylococcus aureus SrrAB Regulatory System Modulates Hydrogen Peroxide Resistance Factors, Which Imparts Protection to Aconitase during Aerobic Growth
Author(s) -
Ameya A. Mashruwala,
Jeffrey M. Boyd
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0170283
Subject(s) - aconitase , regulon , repressor , hydrogen peroxide , cellular respiration , transcription factor , biology , microbiology and biotechnology , transcription (linguistics) , gene , staphylococcus aureus , biochemistry , chemistry , peroxide , genetics , bacteria , mitochondrion , linguistics , philosophy , organic chemistry
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 (H 2 O 2 ) can arise as a byproduct of spontaneous interactions between dioxygen and components of respiratory pathways. H 2 O 2 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 H 2 O 2 intoxication. We tested the hypothesis that SrrAB manages the mutually inclusive expression of genes required for aerobic respiration and H 2 O 2 resistance. Consistent with our hypothesis, a Δ srrAB strain had decreased transcription of genes encoding for H 2 O 2 resistance factors ( kat , ahpC , dps ). SrrAB was not required for the inducing the transcription of these genes in cells challenged with H 2 O 2 . Purified SrrA bound to the promoter region for dps suggesting that SrrA directly influences dps transcription. The H 2 O 2 sensitivity of the Δ srrAB strain was alleviated by iron chelation or deletion of the gene encoding for the peroxide regulon repressor (PerR). The positive influence of SrrAB upon H 2 O 2 metabolism bestowed protection upon the solvent accessible iron-sulfur (FeS) cluster of aconitase from H 2 O 2 poisoning. SrrAB also positively influenced transcription of scdA ( ytfE ), which encodes for a FeS cluster repair protein. Finally, we found that SrrAB positively influences H 2 O 2 resistance only during periods of high dioxygen-dependent respiratory activity. SrrAB did not influence H 2 O 2 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 H 2 O 2 intoxication during respiratory growth upon dixoygen.