A PerR-regulated Metal Transporter (PmtA) Is an Interface Between Oxidative Stress and Metal Homeostasis in Streptococcus Pyogenes

Mol Microbiol. 2007 Feb;63(4):1185-96. doi: 10.1111/j.1365-2958.2006.05577.x.

Abstract

In Streptococcus pyogenes, mutation of the peroxide sensor PerR results in avirulence despite producing hyper-resistance to peroxide stress. To understand the basis of this effect, global transcription profiling was conducted revealing one highly downregulated gene (czcD), and five highly upregulated genes in the mutant. Of the latter, only pmtA contained a binding site for PerR, while phtY, phtD, lsp and rpsN2 harboured an AdcR motif and were regulated by AdcR, a repressor of an ABC-type metal transporter. Furthermore, only the PerR-regulated pmtA (PerR-regulated metal transporter A), a putative metal transporter, contributed to resistance against peroxide stress, while AdcR and the other AdcR-regulated genes did not. However, overexpression of pmtA resulted in upregulation of several AdcR-regulated genes, suggesting that the AdcR regulon is sensitive to PerR regulation of metal homeostasis. Finally, examination of S. pyogenes following murine subcutaneous infection revealed that while pmtA was not upregulated in a late infection, the AdcR-regulated genes were. Taken together, these data suggest that PerR has a greater impact on the transcriptome than can be predicted by its binding sites and that pmtA functions to link metal homeostasis and oxidative stress responses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Binding Sites
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Gene Expression Regulation, Bacterial
  • Homeostasis
  • Hydrogen Peroxide / pharmacology
  • Metals / metabolism*
  • Mice
  • Mutation
  • Oxidative Stress*
  • Regulon
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Streptococcal Infections / genetics
  • Streptococcal Infections / microbiology
  • Streptococcus pyogenes / drug effects
  • Streptococcus pyogenes / genetics
  • Streptococcus pyogenes / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Zinc / pharmacology

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Metals
  • Repressor Proteins
  • Transcription Factors
  • peroxide repressor proteins
  • Hydrogen Peroxide
  • Zinc