Signal-specific temporal response by the Salmonella PhoP/PhoQ regulatory system

Area of Science:

• Microbiology
• Molecular Biology
• Bacterial Pathogenesis

Background:

• The PhoP/PhoQ two-component system regulates critical physiological and virulence functions in Salmonella Typhimurium.
• PhoP acts as a transcriptional activator, but its target gene expression can vary based on PhoQ activation signals.

Purpose of the Study:

• To elucidate the mechanism by which PhoP regulates distinct gene sets in response to different PhoQ-activating signals.
• To investigate the role of the Mg(2+) transporter MgtA in PhoP-mediated gene expression and bacterial resistance.

Main Methods:

• Investigating gene transcription patterns under varying PhoQ activation conditions (low Mg(2+), acidic pH, antimicrobial peptide C18G).
• Assessing the requirement of MgtA for PhoP-activated gene expression.
• Analyzing the impact of MgtA on PhoP phosphorylation and periplasmic Mg(2+) levels.
• Evaluating MgtA-dependent changes in resistance to polymyxin B.

Main Results:

• Full transcription of over half of PhoP-activated genes requires MgtA specifically under low Mg(2+) conditions, but not under acidic pH or C18G activation.
• MgtA facilitates PhoP activation by lowering periplasmic Mg(2+), which is a repressing signal for PhoQ.
• MgtA-dependent gene expression confers enhanced resistance to the antibiotic polymyxin B.
• MgtA production necessitates a drop in cytoplasmic Mg(2+) levels, establishing a tiered temporal response.

Conclusions:

• PhoP/PhoQ signaling exhibits signal-dependent regulation of gene expression through mechanisms involving MgtA.
• MgtA plays a crucial role in modulating PhoP activity and mediating Salmonella's response to specific environmental cues, including Mg(2+) availability.
• This regulatory network contributes to Salmonella's survival and virulence by controlling resistance to cationic antimicrobial agents.