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

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 (PerRBL, PerR2 and PerR3) in addition to Fur and Zur. In the present study, we characterized the role of PerRBL in B. licheniformis. In vitro and in vivo studies indicate that PerRBL, like PerRBS, uses either Fe2+ or Mn2+ as a corepressor and only the Fe2+-bound form of PerRBL senses low levels of H2O2 by iron-mediated histidine oxidation. Interestingly, regardless of the difference in H2O2 sensitivity, if any, between PerRBL and PerRBS, B. licheniformis expressing PerRBL or PerRBS could sense lower levels of H2O2 and was more sensitive to H2O2 than B. subtilis expressing PerRBL or PerRBS. This result suggests that the differences in cellular milieu between B. subtilis and B. licheniformis, rather than the intrinsic differences in PerRBS and PerRBLper 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 (PerRSA), which is more sensitive to H2O2 than PerRBL and PerRBS, were more resistant to H2O2 than those expressing either PerRBL or PerRBS. 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.