The difference in in vivo sensitivity between Bacillus licheniformis PerR and Bacillus subtilis PerR is due to the different cellular environments

Abstract

PerR, a member of Fur family of metal-dependent regulators, is a major peroxide sensor in many Gram positive bacteria, and controls the expression of genes involved in peroxide resistance. Bacillus licheniformis, a close relative to the well-studied model organism Bacillus subtilis, contains three PerR-like proteins (PerR_BL, PerR2 and PerR3) in addition to Fur and Zur. In the present study, we characterized the role of PerR_BL in B. licheniformis. In vitro and in vivo studies indicate that PerR_BL, like PerR_BS, uses either Fe²⁺ or Mn²⁺ as a corepressor and only the Fe²⁺-bound form of PerR_BL senses low levels of H₂O₂ by iron-mediated histidine oxidation. Interestingly, regardless of the difference in H₂O₂ sensitivity, if any, between PerR_BL and PerR_BS, B. licheniformis expressing PerR_BL or PerR_BS could sense lower levels of H₂O₂ and was more sensitive to H₂O₂ than B. subtilis expressing PerR_BL or PerR_BS. This result suggests that the differences in cellular milieu between B. subtilis and B. licheniformis, rather than the intrinsic differences in PerR_BS and PerR_BLper se, affect the H₂O₂ sensing ability of PerR inside the cell and the H₂O₂ resistance of cell. In contrast, B. licheniformis and B. subtilis expressing Staphylococcus aureus PerR (PerR_SA), which is more sensitive to H₂O₂ than PerR_BL and PerR_BS, were more resistant to H₂O₂ than those expressing either PerR_BL or PerR_BS. This result indicates that the sufficient difference in H₂O₂ susceptibility of PerR proteins can override the difference in cellular environment and affect the resistance of cell to H₂O₂.

Keywords: Bacillus licheniformis; Fur (ferric uptake regulator) family; Hydrogen peroxide; PerR (peroxide sensing repressor).