An Iron-Binding Protein, Dpr, Decreases Hydrogen Peroxide Stress and Protects Streptococcus pyogenes against Multiple Stresses

Abstract

Streptococcus pyogenes does not produce catalase, but it can grow in aerobic environments and survive in the presence of peroxide. One of the stress proteins of this organism, peroxide resistance protein (Dpr), has been studied to examine its role in resistance to hydrogen peroxide, but the protective mechanism of Dpr is not clear. The aim of this study was to characterize the dpr gene and its role in dealing with different stresses. A dpr deletion mutant was constructed by double-crossover mutagenesis. The dpr mutant was more sensitive to H 2 O 2 , and complementation could partially restore the defect in the mutant. Pretreatment with the iron chelator deferoxamine mesylate rescued the survival activity of the mutant under oxidative stress conditions. The dpr mutant also showed a low survival rate in the long-term stationary phase, when it was treated with extreme acids, and under alkaline pH conditions compared to the wild-type strain. The growth of the dpr mutant was slower than that of the wild-type strain in iron-limiting conditions. The dpr mutant showed high sensitivity to iron and zinc but not to manganese, copper, nickel, and calcium. Recombinant Dpr protein was purified and showed iron-binding activity, whereas no DNA-binding activity was found. These data indicate that an ironbinding protein, Dpr, provides protection from hydrogen peroxide stress by preventing the Fenton reaction, and Dpr was identified as a novel stress protein that protects against several stresses in group A streptococci.

The PerR-Regulated P 1B-4 -Type ATPase (PmtA) Acts as a Ferrous Iron Efflux Pump in Streptococcus pyogenes

“…Here, we confirm that pmtA expression is upregulated by both Fe(II) and hydrogen peroxide and is regulated via PerR. The GAS ferritin-like protein Dpr (formerly MrgA) is also regulated by PerR (14) and has been shown to chelate Fe and protect GAS under conditions of oxidative stress (46). We hypothesize that GAS uses Dpr and PmtA to sequester and export Fe(II) under oxidative stress conditions, respec-tively.…”

“…Cu(I) and Fe(II) are biologically available metal elements capable of potentiating Fenton chemistry. In the case of Fe(II), one aspect of the bacterial peroxide stress response involves the decreased expression of Fe uptake systems and the increased expression of Fe storage proteins that effectively sequester Fe and thus prevent prooxidant activity (12)(13)(14). In contrast, copper concentrations within the bacterial cell are held very low as a consequence of the action of a Cu efflux system (CopYAZ) that is controlled by a Cu-sensing regulator (CopY) (15)(16)(17).…”

Stress Physiology of Lactic Acid Bacteria

“…An S. pneumoniae ⌬dpr strain displayed a reduced colonization ability and was more rapidly cleared from the nasopharynxes of infected animals (527). Despite the in vitro hypersensitivity to peroxide (528), loss of Dpr did not affect GAS virulence in zebrafish or in different murine infection models (529).…”

Peroxide Stimulon and Role of PerR in Group A Streptococcus

“…A critical role for SodA in GAS aerobic growth has been proposed (18). The iron/DNA-binding protein Dpr/MrgA (Dps-like peroxide resistance protein) is also thought to contribute to resistance against oxidative DNA damage by chelating free intracellular iron, thus preventing its reaction with peroxide (Fenton reaction) and leading to generation of highly reactive hydroxyl radicals (5,65).…”