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

Audrey Brenot, Benjamin F. Weston, Michael G. Caparon

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

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.

Original languageEnglish
Pages (from-to)1185-1196
Number of pages12
JournalMolecular Microbiology
Volume63
Issue number4
DOIs
StatePublished - Feb 2007

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