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

J Appl Microbiol. 2022 Sep;133(3):1422-1433. doi: 10.1111/jam.15644. Epub 2022 Jun 13.

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.

Keywords: A. baumannii; anti-biofilm; auranofin; carbapenem; carbapenemase; synergistic activity.

MeSH terms

  • Acinetobacter Infections* / microbiology
  • Acinetobacter baumannii*
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Auranofin / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / pharmacology
  • Carbapenems / pharmacology
  • Doripenem / pharmacology
  • Drug Resistance, Multiple, Bacterial / genetics
  • Humans
  • Microbial Sensitivity Tests
  • beta-Lactamases / genetics

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carbapenems
  • Auranofin
  • Doripenem
  • beta-Lactamases