Mg2+ as an extracellular signal: environmental regulation of Salmonella virulence

Cell. 1996 Jan 12;84(1):165-74. doi: 10.1016/s0092-8674(00)81003-x.


Ions are not traditionally thought to act as first messengers in signal transduction cascades. However, while searching for genes regulated by the PhoP/PhoQ virulence regulatory system of Salmonella typhimurium, we recovered two loci whose expression is controlled by the concentration of Mg2+. To determine whether Mg2+ is the signal modulating the whole PhoP/PhoQ system, we evaluated the gene expression pattern of six PhoP-activated genes. Growth in physiological concentrations of divalent cations repressed transcription of PhoP-activated genes and rendered wild-type Salmonella phenotypically PhoP-. Mg2+ changed the conformation of the periplasmic domain of PhoQ, identifying this protein as a Mg2+ sensor. A mutation in the sensing domain of PhoQ altered the set point for Mg2+ and rendered Salmonella avirulent.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / physiology
  • Base Sequence
  • Cations / metabolism
  • Gene Expression Regulation, Bacterial / physiology
  • Hydrogen-Ion Concentration
  • Kinetics
  • Magnesium / pharmacology*
  • Molecular Sequence Data
  • Mutation / physiology
  • Peptides / physiology
  • Phenotype
  • Protein Conformation
  • Salmonella typhimurium / pathogenicity*
  • Salmonella typhimurium / physiology*
  • Sensitivity and Specificity
  • Signal Transduction / physiology*
  • Transcription Factors / genetics
  • Virulence


  • Bacterial Proteins
  • Cations
  • Peptides
  • PhoQ protein, Bacteria
  • Transcription Factors
  • PhoP protein, Bacteria
  • Magnesium