Abstract
Iron is an essential nutrient that is implicated in most cellular oxidation reactions. However, iron is a highly reactive element that, if not appropriately chaperoned, can react with endogenously and exogenously generated oxidants such as hydrogen peroxide to generate highly toxic hydroxyl radicals. Dps proteins (DNA-binding proteins from starved cells) form a distinct class (the miniferritins) of iron-binding proteins within the ferritin superfamily. Bacillus anthracis encodes two Dps-like proteins, Dps1 and Dps2, the latter being one of the main iron-containing proteins in the cytoplasm. In this study, the function of Dps2 was characterized in vivo. A B. anthracis Δdps2 mutant was constructed by double-crossover mutagenesis. The growth of the Δdps2 mutant was unaffected by excess iron or iron-limiting conditions, indicating that the primary role of Dps2 is not that of iron sequestration and storage. However, the Δdps2 mutant was highly sensitive to H(2)O(2), and pretreatment of the cells with the iron chelator deferoxamine mesylate (DFM) significantly reduced its sensitivity to H(2)O(2) stress. In addition, the transcription of dps2 was upregulated by H(2)O(2) treatment and derepressed in a perR mutant, indicating that dps2 is a member of the regulon controlled by the PerR regulator. This indicates that the main role of Dps2 is to protect cells from peroxide stress by inhibiting the iron-catalyzed production of OH.