Overcoming Nanosilver Resistance: Resensitizing Bacteria and Targeting Evolutionary Mechanisms

Area of Science:

• Environmental Science
• Microbiology
• Materials Science

Background:

• Antimicrobial resistance (AMR) is a critical global health and environmental concern.
• Antimicrobial nanomaterials, such as silver nanoparticles (AgNPs), offer potential solutions but face challenges from emerging nanoresistance.
• Understanding nanoresistance mechanisms is crucial for developing effective antievolutionary strategies.

Purpose of the Study:

• To investigate the dynamic resistance mechanisms of AgNPs.
• To develop targeted physicochemical interventions to overcome AgNP nanoresistance.
• To halt the evolution of resistance against nanoantimicrobials.

Main Methods:

• Characterized AgNP resistance mechanisms, identifying a transition from flagellin-mediated precipitation (state I) to copper efflux pump (CusCFBA) system activation (state II).
• Implemented targeted interventions: energy supply blocking for state I and intracellular acidic pH neutralization for state II.
• Disrupted energy supply and overactivated sigma E to halt resistance evolution.

Main Results:

• Physicochemical interventions reduced AgNP nanoresistance and tolerance by up to 10,000-fold.
• Energy supply blocking effectively counteracted state I resistance.
• Neutralizing intracellular acidic pH significantly reduced state II resistance.
• Resistance evolution was completely halted by combined energy disruption and sigma E overactivation.

Conclusions:

• Developed practical strategies to overcome AgNP nanoresistance.
• Demonstrated the efficacy of targeted interventions in enhancing nanoantimicrobial effectiveness.
• Provided a groundbreaking approach to combat resistance evolution in nanoantimicrobial therapies.