Overcoming Nanosilver Resistance: Resensitizing Bacteria and Targeting Evolutionary Mechanisms
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- envelope stress, evolutionary transition, nanoresistance, resensitization, silver nanoparticle,
- MeSH
- Anti-Bacterial Agents * pharmacology chemistry MeSH
- Bacteria drug effects metabolism MeSH
- Drug Resistance, Bacterial drug effects MeSH
- Escherichia coli drug effects metabolism MeSH
- Metal Nanoparticles * chemistry MeSH
- Microbial Sensitivity Tests * MeSH
- Silver * chemistry pharmacology MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Anti-Bacterial Agents * MeSH
- Silver * MeSH
The rapid spread of antimicrobial resistance poses a critical threat to global health and the environment. Antimicrobial nanomaterials, including silver nanoparticles (AgNPs), are being explored as innovative solutions; however, the emergence of nanoresistance challenges their effectiveness. Understanding resistance mechanisms is essential for developing antievolutionary strategies. AgNPs exhibit diverse resistance mechanisms, and our findings reveal a dynamic transition between these mechanisms: from flagellin-mediated AgNP precipitation (state I) to activation of the copper efflux pump (CusCFBA) system (state II). We designed targeted physicochemical interventions to counteract these mechanisms. Energy supply blocking was effective for state I, while for state II, neutralizing intracellular acidic pH significantly reduced resistance. These strategies reduced nanoresistance/tolerance by up to 10,000-fold. Additionally, resistance evolution can be completely halted by disrupting the energy supply using carbonyl cyanide 3-chlorophenylhydrazone and overactivating sigma E, one of the key envelope stress regulators that govern resistance transitions. Our findings provide practical strategies to overcome nanoresistance, offering a groundbreaking approach to enhance nanoantimicrobials' efficacy in medical therapies and combat resistance evolution.
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