A genetic switch controls Pseudomonas aeruginosa surface colonization

Area of Science:

• Microbiology
• Molecular Biology
• Infectious Diseases

Background:

• Efficient colonization of mucosal surfaces is crucial for opportunistic pathogens like Pseudomonas aeruginosa.
• Mechanisms governing bacterial adaptation for adherence, virulence, and dispersal remain largely unclear.

Purpose of the Study:

• To identify genetic mechanisms controlling Pseudomonas aeruginosa surface colonization and dispersal.
• To investigate the role of the hecR-hecE genetic switch in bacterial adaptation.
• To explore the HecE pathway as a potential therapeutic target.

Main Methods:

• Identified a stochastic genetic switch, hecR-hecE, exhibiting bimodal expression.
• Investigated the role of HecE in regulating cyclic diguanylate monophosphate (c-di-GMP) levels.
• Assessed the impact of HecE expression on bacterial subpopulations and community behavior.
• Evaluated the HecE pathway as a druggable target.

Main Results:

• The hecR-hecE switch generates distinct subpopulations: HecE-high cells promote colonization, while HecE-low cells disperse.
• HecE modulates c-di-GMP levels by inhibiting BifA and stimulating WspR.
• The proportion of HecE+ cells is influenced by stress factors, balancing biofilm formation and dispersal.
• The HecE pathway was confirmed as a druggable target for controlling P. aeruginosa surface colonization.

Conclusions:

• The HecE pathway represents a novel mechanism for balancing growth and dispersal in P. aeruginosa.
• Targeting this pathway offers a promising strategy to combat mucosal infections caused by this pathogen.
• Understanding these binary states provides new avenues for controlling P. aeruginosa surface colonization.