title: Regulation of Salmonella enterica serovar Typhimurium mntH transcription by H(2)O(2), Fe(2+), and Mn(2+).
abstract: MntH, a bacterial homolog of mammalian natural resistance associated macrophage protein 1 (Nramp1), is a primary transporter for Mn(2+) influx in Salmonella enterica serovar Typhimurium and Escherichia coli. S. enterica serovar Typhimurium MntH contributes to H(2)O(2) resistance and is important for full virulence. Consistent with its phenotype and function, mntH is regulated at the transcriptional level by both H(2)O(2) and substrate cation. We have now identified three trans-acting regulatory factors and the three corresponding cis-acting mntH promoter motifs that mediate this regulation. In the presence of hydrogen peroxide, mntH is activated by OxyR, acting through an OxyR-binding motif centered just upstream of the likely -35 RNA polymerase-binding site. In the presence of Fe(2+), mntH is repressed primarily by Fur, acting through a Fur-binding motif overlapping the -35 region. In the presence of Mn(2+), mntH is repressed primarily by the Salmonella equivalent of E. coli b0817, a distant homolog of the Bacillus subtilis manganese transport repressor, MntR, acting through an inverted-repeat motif located between the likely -10 polymerase binding site and the ribosome binding site. E. coli b0817 was recently shown to bind the identical inverted-repeat motif in the E. coli mntH promoter and hence has been renamed MntR (S. I. Patzer and K. Hantke, J. Bacteriol. 183:4806-4813, 2001). Using Deltafur, DeltamntR, and Deltafur DeltamntR mutant strains as well as mutations in the Fur- and MntR-binding motif elements, we found that Fe(2+) can also mediate repression through the Mn(2+) repressor MntR.
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4965, USA. dgk2@po.cwru.edu
authors.forename: David G
authors.initials: DG
authors.lastname: Kehres
authors.forename: Anu
authors.initials: A
authors.lastname: Janakiraman
authors.forename: James M
authors.initials: JM
authors.lastname: Slauch
authors.forename: Michael E
authors.initials: ME
authors.lastname: Maguire
mesh_terms: D001426:Bacterial Proteins; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins; D029968:Escherichia coli Proteins; D005296:Ferrous Compounds / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D029968:Escherichia coli Proteins; D005296:Ferrous Compounds; C492412:MntH protein, E coli; C433793:MntH protein, bacteria; D012097:Repressor Proteins; D008345:Manganese; D006861:Hydrogen Peroxide