Characterization of synergistic antibacterial effect of silver nanoparticles and ebselen

Abstract

The emerging and spreading of multi-drug resistant (MDR) bacteria have been becoming one of the most severe threats to human health. Enhancing oxidative stress as mimicking immune system was considered as a potential strategy to fight against infection of MDR bacteria. In this study, we investigated the antibacterial efficiency of such a strategy which combines silver nanoparticles (AgNPs) with ebselen. The results showed that AgNPs and ebselen combination had significant synergistic killing effects both on <i>Escherichia coli</i> (<i>E. coli</i>) and <i>Staphylococcus aureus</i> (<i>S. aureus</i>) <i>in vitro</i>, including model strains of China Veterinary Culture Collection and MDR clinical isolates, which is similar as the combination of silver ion and ebselen. AgNPs exhibited to be a strong inhibitor of bacterial thioredoxin reductase, same as a free silver ion. Ebselen mitigated the cytotoxicity of AgNPs to HeLa cells. However, in a bacteria-cell coexistence condition, the synergistic bactericidal effect was only observed on <i>S. aureus</i> (<i>p</i><.05), while the temporary synergistic inhibitory effect on <i>E. coli</i> within 4 hours treatment (<i>p</i><.01). In mice infection model, a combination of AgNPs and ebselen did not increase protection against the challenge of clinical <i>E. coli</i> CQ10 strain. Our data demonstrated that AgNPs and ebselen combination may be a promising strategy to fight against the increasingly MDR bacteria targeting bacterial thiol redox system.