Negligible Particle-Specific Antibacterial Activity of Silver Nanoparticles

For nearly a decade, researchers have debated the mechanisms by which AgNPs exert toxicity to bacteria and other organisms. The most elusive question has been whether the AgNPs exert direct "particle-specific" effects beyond the known antimicrobial activity of released silver ions (Ag+). Here, we infer that Ag+ is the definitive molecular toxicant. We rule out direct particle-specific biological effects by showing the lack of toxicity of AgNPs when synthesized and tested under strictly anaerobic conditions that preclude Ag(0) oxidation and Ag+ release. Furthermore, we demonstrate that the toxicity of various AgNPs (PEG- or PVP- coated, of three different sizes each) accurately follows the dose response pattern of E. coli exposed to Ag+ (added as AgNO3). Surprisingly, E. coli survival was stimulated by relatively low (sublethal) concentration of all tested AgNPs and AgNO3 (at 3-8 mu g/L Ag+, or 12-31% of the minimum lethal concentration (MLC)), suggesting a hormetic response that would be counterproductive to antimicrobial applications. Overall, this work suggests that AgNP morphological properties known to affect antimicrobial activity are indirect effectors that primarily influence Ag+ release. Accordingly, antibacterial activity could be controlled (and environmental impacts could be mitigated) by modulating Ag+ release, possibly through manipulation of oxygen availability, particle size, shape, and/or type of coating.