The global transcriptional response of Bacillus subtilis to manganese involves the MntR, Fur, TnrA and sigmaB regulons

Mol Microbiol. 2003 Sep;49(6):1477-91. doi: 10.1046/j.1365-2958.2003.03648.x.


We have used DNA microarrays to monitor the global transcriptional response of Bacillus subtilis to changes in manganese availability. Mn(II) leads to the MntR-dependent repression of both the mntH and mntABCD operons encoding Mn(II) uptake systems. Mn(II) also represses the Fur regulon. This repression is unlikely to be a direct effect of Mn(II) on Fur as repression is sensitive to 2,2'-dipyridyl, an iron-selective chelator. We suggest that elevated Mn(II) displaces iron from cellular-binding sites and the resulting rise in free iron levels leads to repression of the Fur regulon. Many of the genes induced by Mn(II) are activated by sigmaB or TnrA. Both of these regulators are controlled by Mn(II)-dependent enzymes. Induction of the sigmaB-dependent general stress response by Mn(II) is largely dependent on RsbU, a Mn(II)-dependent phosphatase that dephosphorylates RsbV, ultimately leading to release of active sigmaB from its antisigma, RsbW. The activity of TnrA is inhibited when it forms an inactive complex with feedback-inhibited glutamine synthetase. Elevated Mn(II) reduces the sensitivity of glutamine synthetase to feedback inhibitors, and we suggest that this leads to the observed increase in TnrA activity. In sum, three distinct mechanisms can account for most of the transcriptional effects elicited by manganese: (i) direct binding of Mn(II) to metalloregulators such as MntR, (ii) perturbation of cellular iron pools leading to increased Fur activity and (iii) altered activity of Mn(II)-dependent enzymes that regulate the activity of sigmaB and TnrA.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacillus subtilis / genetics*
  • Bacillus subtilis / growth & development
  • Bacillus subtilis / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Base Sequence
  • DNA Footprinting
  • Gene Expression Regulation, Bacterial*
  • Genes, Reporter / genetics
  • Ion Transport / genetics
  • Ion Transport / physiology
  • Iron / metabolism
  • Manganese / metabolism*
  • Manganese / pharmacology*
  • Metalloproteins / metabolism
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism
  • Regulon*
  • Repressor Proteins / genetics
  • Repressor Proteins / isolation & purification
  • Repressor Proteins / metabolism
  • Sigma Factor / genetics
  • Sigma Factor / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • beta-Galactosidase / metabolism


  • Bacterial Proteins
  • Metalloproteins
  • MntR protein, bacteria
  • Repressor Proteins
  • ScgR protein, Bacillus subtilis
  • SigB protein, Bacteria
  • Sigma Factor
  • Transcription Factors
  • ferric uptake regulating proteins, bacterial
  • Manganese
  • Iron
  • Phosphoric Monoester Hydrolases
  • RsbU protein, Bacillus subtilis
  • beta-Galactosidase