A PerR‐regulated metal transporter (PmtA) is an interface between oxidative stress and metal homeostasis inStreptococcus pyogenes

Abstract

SummaryIn 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.

Protective capacities of cell surface-associated proteins of Streptococcus suis mutants deficient in divalent cation-uptake regulators

“…Scenarios in concordance with this hypothesis have been reported during zinc starvation for ribosomal proteins of B. subtilis and Streptococcus pyogenes (Brenot et al, 2007;Makarova et al, 2001). In accordance with this, our results showed that expression of ssu1352 ORF in the adcR-knockout strain, encoding ribosomal protein S14, is approximately 100-fold higher than in the wild-type strain (Fig.…”

“…Furthermore, Pht proteins are involved in the host-cellpathogen interaction, and it has been hypothesized that they have evolved to become sensitive to AdcR regulation in order to exploit zinc as a compartment-specific regulatory cue (Brenot et al, 2007). It is also noteworthy that Pht proteins present hydrophobic leader sequences, which presumably target these proteins to the bacterial cell surface and induce specific antibodies against pneumococcal sepsis, suggesting that Pht proteins could serve as effective vaccines against streptococcal infections (Adamou et al, 2001;Kunitomo et al, 2008).…”

Transcriptional regulation, occurrence and putative role of the Pht family of Streptococcus pneumoniae

“…Binding of AdcR, induced under conditions of high Zn 2+ concentration, inhibits the transcription of the genes under its dependence. Upon direct or indirect zinc starvation conditions, and hence a reduced intracellular concentration of this metal, repression by AdcR is relieved (Brenot et al, 2007;Claverys, 2001). However, and in contrast to what we have observed here, it was recently shown that the addition of zinc in culture medium elicits Pht production (Ogunniyi et al, 2009).…”

Peroxide‐Sensing Transcriptional Regulators in Bacteria

“…In Bacillus subtilis, PerR regulates itself (30) and other genes, including those involved in oxidative stress defense (katA, ahpCF, mrgA) (10,14), metal homeostasis (zosA, fur, hemAXCDBL) (14,30,31), and surfactant production (srfA) (41), in response to peroxide exposure. As with OxyR, PerR homologs in other organisms tend to regulate similar classes of genes (7,8,36,48,79,91,117).…”