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 Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in vitro, 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 S. aureus (p<.05), while the temporary synergistic inhibitory effect on E. coli within 4 hours treatment (p<.01). In mice infection model, a combination of AgNPs and ebselen did not increase protection against the challenge of clinical E. coli 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.
Keywords: Silver nanoparticles; ebselen; multi-drug resistance bacteria; oxidative stress; synergistic antibacterial effect; thioredoxin reductase.