Peroxide responsive regulator PerR of group A Streptococcus is required for the expression of phage-associated DNase Sda1 under oxidative stress

PLoS One. 2013 Dec 3;8(12):e81882. doi: 10.1371/journal.pone.0081882. eCollection 2013.

Abstract

The peroxide regulator (PerR) is a ferric uptake repressor-like protein, which is involved in adaptation to oxidative stress and iron homeostasis in group A streptococcus. A perR mutant is attenuated in surviving in human blood, colonization of the pharynx, and resistance to phagocytic clearance, indicating that the PerR regulon affects both host environment adaptation and immune escape. Sda1 is a phage-associated DNase which promotes M1T1 group A streptococcus escaping from phagocytic cells by degrading DNA-based neutrophil extracellular traps. In the present study, we found that the expression of sda1 is up-regulated under oxidative conditions in the wild-type strain but not in the perR mutant. A gel mobility shift assay showed that the recombinant PerR protein binds the sda1 promoter. In addition, mutation of the conserved histidine residue in the metal binding site of PerR abolished sda1 expression under hydrogen peroxide treatment conditions, suggesting that PerR is directly responsible for the sda1 expression under oxidative stress. Our results reveal PerR-dependent sda1 expression under oxidative stress, which may aid innate immune escape of group A streptococcus.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Bacteriophages / physiology*
  • Binding Sites
  • Deoxyribonuclease I / genetics*
  • Gene Expression Regulation, Bacterial*
  • Metals / metabolism
  • Molecular Sequence Data
  • Mutation
  • Oxidative Stress*
  • Promoter Regions, Genetic / genetics
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Streptococcus pyogenes / genetics
  • Streptococcus pyogenes / metabolism*
  • Streptococcus pyogenes / virology*
  • Transcription Initiation Site

Substances

  • Bacterial Proteins
  • Metals
  • Repressor Proteins
  • peroxide repressor proteins
  • Deoxyribonuclease I
  • Sda1 protein, Streptococcus pyogenes

Grants and funding

This work was supported in part by grants NSC 98-2320-B-006-006-MY3 and NSC 101-2320-B-006-029-MY3 from the National Science Council, Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.