Mg2+ as an extracellular signal: environmental regulation of Salmonella virulence.
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.
Washington University School of Medicine, Department of Molecular Microbiology, St. Louis, Missouri 63110, USA.
E
E
García Véscovi
F C
FC
Soncini
E A
EA
Groisman
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D001483:Base Sequence; D002412:Cations / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D010455:Peptides / Q000502:physiology; D010641:Phenotype; D011487:Protein Conformation; D012486:Salmonella typhimurium / Q000472:pathogenicity* / Q000502:physiology*; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D014774:Virulence
D001426:Bacterial Proteins; D002412:Cations; D010455:Peptides; C079792:PhoQ protein, Bacteria; D014157:Transcription Factors; C061064:PhoP protein, Bacteria; D008274:Magnesium