title: Manganese homeostasis in Bacillus subtilis is regulated by MntR, a bifunctional regulator related to the diphtheria toxin repressor family of proteins.
abstract: The Bacillus subtilis yqhN gene encodes a metalloregulatory protein distantly related to the Corynebacterium diphtheriae diphtheria toxin repressor (DtxR). While DtxR mediates the iron-dependent repression of iron uptake, we demonstrate that yqhN (herein renamed mntR) encodes a manganese modulated regulator of manganese transport. An mntR mutant strain is sensitive to both manganese and cadmium, suggesting that the transport of these metals is derepressed. We selected Tn10 insertions that suppress the Mn(II) sensitivity of the mntR mutant or that increase the Cd(II) tolerance of wild-type cells, 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 MntH and MntABCD transporters are both selectively repressed by Mn(II) and this 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 conditions. Biochemical studies demonstrate that MntR binding to the mntH control region requires Mn(II), while interaction with the mntABCD control region does not depend on Mn(II).
authors.affiliation: Section of Microbiology, Wing Hall, Cornell University, Ithaca, NY 14853-8101, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Que
authors.forename: J D
authors.initials: JD
authors.lastname: Helmann
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D001692:Biological Transport; D002104:Cadmium / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins; D004167:Diphtheria Toxin / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006706:Homeostasis; D008345:Manganese / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D009876:Operon; D013171:Spores, Bacterial / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D004167:Diphtheria Toxin; C400921:mntA protein, Lactobacillus plantarum; D002104:Cadmium; D008345:Manganese