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 (PerR, PerR2 and PerR3) in addition to Fur and Zur. In the present study, we characterized the role of PerR in B. licheniformis. In vitro and in vivo studies indicate that PerR, like PerR, uses either Fe or Mn as a corepressor and only the Fe-bound form of PerR senses low levels of HO by iron-mediated histidine oxidation. Interestingly, regardless of the difference in HO sensitivity, if any, between PerR and PerR, B. licheniformis expressing PerR or PerR could sense lower levels of HO and was more sensitive to HO than B. subtilis expressing PerR or PerR. This result suggests that the differences in cellular milieu between B. subtilis and B. licheniformis, rather than the intrinsic differences in PerR and PerRper se, affect the HO sensing ability of PerR inside the cell and the HO resistance of cell. In contrast, B. licheniformis and B. subtilis expressing Staphylococcus aureus PerR (PerR), which is more sensitive to HO than PerR and PerR, were more resistant to HO than those expressing either PerR or PerR. This result indicates that the sufficient difference in HO susceptibility of PerR proteins can override the difference in cellular environment and affect the resistance of cell to HO.