Regulation of Salmonella enterica Serovar Typhimurium mntH Transcription by H 2 O 2 , Fe 2+ , and Mn 2+

Abstract

ABSTRACT MntH, a bacterial homolog of mammalian natural resistance associated macrophage protein 1 (Nramp1), is a primary transporter for Mn 2+ influx in Salmonella e nterica 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 Δ fur , Δ mntR , and Δ fur Δ mntR 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.