Sonoporation-enhanced the antibacterial efficacy of aminoglycosides against Gram-negative persisters

Area of Science:

• Microbiology
• Biophysics
• Antimicrobial Therapy

Background:

• Bacterial persisters are dormant cells tolerant to antibiotics, leading to treatment failure and chronic infections.
• Developing strategies to eliminate persisters is critical for effective antibiotic therapy.

Purpose of the Study:

• To investigate the efficacy of low-frequency ultrasound in combination with aminoglycosides (AGs) against bacterial persisters.
• To elucidate the mechanism by which ultrasound enhances antibiotic efficacy against Gram-negative bacteria.

Main Methods:

• Development of a low-frequency (40 kHz) and low-intensity (0.2 W/cm²) ultrasound system.
• Combination therapy of ultrasound with AGs against Gram-negative bacterial persisters (E. coli, P. aeruginosa, A. baumannii).
• Assessment of bacterial membrane permeability using SEM, NPN, PI staining, ONPG assays, and inhibition zone tests; investigation of mechanosensitive channel roles.

Main Results:

• Ultrasound-AG combination therapy reduced persister ratios by 5- to 15-fold in Gram-negative bacteria.
• Complete eradication of MG1655 persisters below the detection threshold (< 2 CFU/mL) was achieved.
• Ultrasound enhanced AG uptake by increasing outer membrane permeability without significant inner membrane damage, potentially via MscK and YbiO channels.

Conclusions:

• Ultrasound-aminoglycoside combination therapy is a promising strategy for eradicating bacterial persisters, particularly in Gram-negative infections.
• This approach offers new insights into bacterial persister physiology and their susceptibility to physical and chemical interventions.
• Ultrasound-induced sonoporation enhances antibiotic delivery by modulating bacterial membrane permeability.