Efflux pumps mediate changes to fundamental bacterial physiology via membrane potential

Area of Science:

• Microbiology
• Bacterial Physiology
• Antimicrobial Resistance

Background:

• Efflux pumps remove antibiotics from bacteria, contributing to antimicrobial resistance.
• Loss of efflux pump function is primarily observed in actively growing cells.
• Salmonella Typhimurium's envelope changes during growth, affecting antibiotic permeability.

Purpose of the Study:

• To investigate the impact of deleting the major efflux pump (AcrB) in Salmonella Typhimurium on global gene transcription.
• To understand how AcrB deletion affects bacterial growth, metabolism, and membrane potential.
• To explore the regulatory mechanisms linking efflux pumps to the transition to stationary phase.

Main Methods:

• Deletion of the AcrB efflux pump in Salmonella Typhimurium.
• Global transcriptome analysis across different growth phases.
• Measurement of membrane potential and analysis of gene expression regulators.

Main Results:

• AcrB knockout strains entered stationary phase later than wild-type.
• Increased and prolonged expression of anaerobic energy metabolism genes was observed.
• AcrB deletion led to increased membrane potential and hyperpolarization.
• A model was proposed where ArcBA senses redox state changes to regulate growth phase transition.

Conclusions:

• Efflux pump deactivation significantly alters bacterial physiology and metabolism.
• Efflux pumps play a crucial role in maintaining membrane potential and energy metabolism.
• Inhibiting efflux pumps may enhance antibiotic activity by prolonging accumulation and potentially increasing reactive species generation.
• Changes in bacterial physiology due to efflux pump inactivation may explain decreased virulence in mutants.