COORDINATE REGULATION OF BACILLUS-SUBTILIS PEROXIDE STRESS GENES BY HYDROGEN-PEROXIDE AND METAL-IONS

The Bacillus subtilis mrgA gene encodes an abundant DNA-binding protei n that protects cells against the lethal effects of H2O2. Transcriptio n of mrgA is induced by H2O2 or by entry into stationary phase when ma nganese and iron levels are low. We have selected for strains derepres sed for transcription of mrgA in the presence of Mn(II). The resulting cis-acting mutants define an operator site just upstream of the mrgA promoter. Similar sequences flank the promoters for the catalase gene, katA, and the heme biosynthesis operon, hemAXCDBL. Like mrgA, transcr iption of the katA and hem genes is repressed by Mn(II), which thereby potentiates the killing action of H2O2. We identified two classes of trans-acting mutants derepressed for mrgA transcription in the presenc e of Mn(II): some exhibit a coordinate derepression of MrgA, catalase, heme biosynthesis, and alkyl hydroperoxide reductase and are H2O2 res istant, while others have reduced catalase activity and are H2O2 sensi tive, These data indicate that the peroxide stress response of B. subt ilis is regulated by a repressor that senses both metal ion levels and H2O2.