Inhibition of bacterial and fungal pathogens by the orphaned drug auranofin

Future Med Chem. 2016;8(2):117-32. doi: 10.4155/fmc.15.182. Epub 2016 Jan 25.

Abstract

Background: We identified auranofin as an antimicrobial compound utilizing a high-throughput screen using a Caenorhabditis elegans-Staphylococcus aureus infection model. Results/methodology: Treatment of infected nematodes with auranofin resulted in a prolonged survival rate of 95%, reached with 0.78 μg/ml. Further investigation of the antimicrobial activity of auranofin found inhibition against S. aureus, Enterococcus faecium and Enterococcus faecalis. Importantly, the fungal pathogens Cryptococcus neoformans was also effectively inhibited with an MIC at 0.5 μg/ml. Auranofin appears to target the thioredoxin system.

Conclusion: This work provides extensive additional data on the antibacterial effects of auranofin that includes both reference and clinical isolates and reports a novel inhibition of fungal pathogens by this compound.

Keywords: Bucillus subtilis; Candida albicans; Cryptococcus neoformans; Enterococcus faecalis; Enterococcus faecium; Staphylococcus aureus; antimicrobial; auranofin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Auranofin / chemistry
  • Auranofin / pharmacology*
  • Bacteria / drug effects
  • Caenorhabditis elegans / drug effects
  • Cryptococcus / drug effects
  • Enterococcus / drug effects
  • Fungi / drug effects
  • Microbial Sensitivity Tests
  • Staphylococcus aureus / drug effects
  • Thioredoxins / antagonists & inhibitors
  • Thioredoxins / metabolism

Substances

  • Anti-Bacterial Agents
  • Auranofin
  • Thioredoxins