A pH-sensitive switch activates virulence in Salmonella

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Salmonella Typhimurium transitions between virulent and biofilm lifestyles, regulated by SsrB.
• Phosphorylated SsrB activates Salmonella Pathogenicity Island-2 (SPI-2) genes for intracellular survival.
• Low vacuolar pH induces SsrB expression and activation, but the molecular mechanism was unclear.

Purpose of the Study:

• To elucidate the molecular mechanism of pH-dependent SsrB activation.
• To investigate the in vivo significance of this pH-sensing mechanism.

Main Methods:

• Single-molecule assays
• Transcriptional assays
• Site-directed mutagenesis (His12 substitution)

Main Results:

• The SsrB DNA-binding domain alone (SsrBc) does not confer pH sensitivity.
• Histidine 12 (His12) in the receiver domain allosterically confers pH sensitivity to SsrB.
• His12 is crucial for SsrB phosphorylation and acid-dependent DNA binding, which is highly cooperative.
• SsrB mutations affecting pH sensing render Salmonella avirulent.

Conclusions:

• His12 is the key residue mediating Salmonella SsrB's pH-dependent activation.
• This mechanism involves allosteric regulation and cooperative DNA binding.
• Targeting the SsrB pH-switch offers a potential strategy to control Salmonella virulence.