Manganese homeostasis in Bacillus subtilis is regulated by MntR, a bifunctional regulator related to the diphtheria toxin repressor family of proteins

The Bacillus subtilis yqhN gene encodes a metalloregulatory protein distant ly related to the Corynebacterium diphtheriae diphtheria toxin repressor (D txR). While DtxR mediates the iron-dependent repression of iron uptake, we demonstrate that yqhN (herein renamed mntR) encodes a manganese modulated r egulator of manganese transport. An mntR mutant strain is sensitive to both manganese and cadmium, suggesting that the transport of these metals is de repressed. We selected Tn10 insertions that suppress the Mn(II) sensitivity of the mntR mutant or that increase the Cd(II) tolerance of wild-type cell s, and in both cases we recovered insertions in mntH (formerly ydaR). MntH is a member of the NRAMP family of proton-coupled, metal ion transporters. MntR also regulates expression of a Mn(II) ABC transporter (MntABCD). The M ntH and MntABCD transporters are both selectively repressed by Mn(II) and t his regulation requires MntR. In high Mn(II) conditions, MntR functions as a Mn(II)-dependent repressor of mntH transcription. In contrast, MntR acts as a positive regulator of the mntABCD operon under low Mn(II) growth condi tions. Biochemical studies demonstrate that MntR binding to the mntH contro l region requires Mn(II), while interaction with the mntABCD control region does not depend on Mn(II).