Mode of action of silver-based perovskite against Gram-negative bacteria

Although silver is known for its antibacterial activity, its exact mode of action remains unclear. In our previous work, we described AgNbO₃ nanoparticles (AgNbO₃ NPs) prepared using a ceramic method, followed by high-energy and low-energy ball-milling processes, which exhibited antimicrobial activity with negligible release of Ag⁺ in deionized water. Here, we investigated thoroughly the mode of action of these AgNbO₃ NPs against <i>Escherichia coli</i>. Drastic morphological changes in <i>E. coli</i> were observed after their exposure to AgNbO₃ NPs. In addition to cellular damage, AgNbO₃ NPs induced the production of reactive oxygen species and lipid peroxidation, likely following the release of small amounts of Ag⁺. This was concluded from the characterization of mutants resistant to AgNbO₃ NPs that showed cross-resistance to AgNO₃, impaired reactive oxygen species production and lipid peroxidation, and harbored a key mutation in a two-component regulatory system regulating an Ag⁺ efflux pump. We calculated, however, that the quantity of Ag⁺ released from AgNbO₃ NPs is not sufficient by itself to lead to bacterial death. We propose that bacterial contact with the AgNbO₃ NPs in combination with Ag⁺ release is necessary for the mode of action of AgNbO₃ NPs.IMPORTANCESilver is known for its antibacterial activity, but its exact mode of action remains unclear. Here, we investigated thoroughly the mode of action of AgNbO₃ nanoparticles against <i>Escherichia coli</i>. Our data suggest that AgNbO₃ nanoparticles have dual effects on the cell and that both are required for its lethal action.