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Updated: Jul 17, 2026

Essential Metal Uptake in Gram-negative Bacteria: X-ray Fluorescence, Radioisotopes, and Cell Fractionation
Published on: February 1, 2018
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.
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.
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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