Auranofin promotes antibacterial effect of doripenem against carbapenem-resistant Acinetobacter baumannii

Abstract

Aims: This study was performed to identify the potential for repurposing auranofin as an antibiotic adjuvant against carbapenemase-producing Acinetobacter baumannii. Methods and Results: The clinically isolated A. baumannii strains used in this study were all resistant to carbapenems and harboured the blaOXA-23 gene. The synergistic effect of auranofin and doripenem against carbapenemase-producing A. baumannii was confirmed through checkerboard and growth kinetic analyses. This study also demonstrated the inhibitory effects of auranofin against A. baumannii biofilms. The anti-biofilm effects of auranofin were visualized by confocal laser scanning microscopy (CLSM). Furthermore, auranofin inhibited motility, one of the virulence factors. Additionally, the changes in the expression of carbapenemase-, biofilm- and efflux pump-related genes induced by auranofin were confirmed via quantitative polymerase chain reaction (qPCR). Conclusions: Our results demonstrated that auranofin has an antibacterial effect with doripenem and an inhibitory effect on several factors related to carbapenem resistance. Significance and Impact of the Study: This study suggests that auranofin is a promising antibiotic adjuvant that can be used to prevent antibiotic resistance in carbapenem-resistant A. baumannii.