A PerR-regulated metal transporter (PmtA) is an interface between oxidative stress and metal homeostasis in

Audrey Brenot1, Benjamin F Weston, Michael G Caparon

  • 1Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110, USA.

Molecular Microbiology
|January 24, 2007
PubMed

Insights

Mutation of the peroxide sensor PerR in Streptococcus pyogenes leads to avirulence and increased peroxide resistance. The PerR-regulated gene pmtA links metal homeostasis and oxidative stress responses.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Streptococcus pyogenes PerR is a peroxide sensor.
  • PerR mutations cause avirulence and peroxide resistance.
  • Global transcription profiling is used to study gene regulation.

Purpose of the Study:

  • To understand the molecular basis of PerR-mediated avirulence in S. pyogenes.
  • To identify genes regulated by PerR and AdcR.
  • To elucidate the link between metal homeostasis and oxidative stress response.

Main Methods:

  • Global transcription profiling (RNA sequencing) of a PerR mutant.
  • Identification of transcription factor binding sites (PerR and AdcR motifs).
  • Analysis of gene expression during murine infection models.

Main Results:

  • PerR mutation downregulated cczD and upregulated five genes, including pmtA (PerR-regulated) and AdcR-regulated genes.
  • Only pmtA contributed to peroxide resistance.
  • pmtA overexpression upregulated AdcR-regulated genes, indicating PerR's influence on metal homeostasis.
  • AdcR-regulated genes were upregulated during murine infection, not pmtA.

Conclusions:

  • PerR significantly impacts the S. pyogenes transcriptome beyond its direct binding sites.
  • pmtA acts as a crucial link between metal homeostasis and oxidative stress responses.
  • AdcR-regulated genes play a role in S. pyogenes pathogenesis.

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