Auranofin inhibits virulence pathways in Pseudomonas aeruginosa

Research output: Contribution to journalJournal articlepeer-review

  • Joey Kuok Hoong Yam
  • Leon Zhen Wei Tan
  • Ziyan Hong
  • May Margarette Santillan Salido
  • Bau Yi Woo
  • Adeline Mei Hui Yong
  • Casandra Ai Zhu Tan
  • Sam Fong Yau Li
  • Liang Yang
  • Givskov, Michael
  • Shu Sin Chng

Pseudomonas aeruginosa is widely attributed as the leading cause of hospital-acquired infections. Due to intrinsic antibiotic resistance mechanisms and the ability to form biofilms, P. aeruginosa infections are challenging to treat. P. aeruginosa employs multiple virulence mechanisms to establish infections, many of which are controlled by the global virulence regulator Vfr. An attractive strategy to combat P. aeruginosa infections is thus the use of anti-virulence compounds. Here, we report the discovery that FDA-approved drug auranofin attenuates virulence pathways in P. aeruginosa, including quorum sensing (QS) and Type IV pili (TFP). We show that auranofin acts via multiple targets, one of which being Vfr. Consistent with inhibition of QS and TFP expression, we show that auranofin attenuates biofilm maturation, and when used in combination with colistin, displays strong synergy in eradicating P. aeruginosa biofilms. Auranofin may have immediate applications as an anti-virulence drug against P. aeruginosa infections.

Original languageEnglish
Article number117167
JournalBioorganic and Medicinal Chemistry
Volume79
ISSN0968-0896
DOIs
Publication statusPublished - 2023

Bibliographical note

Funding Information:
We thank Young-Tae Chang (POSTECH) for allowing access to small molecule libraries used in this study. We acknowledge Song Lin Chua (SCELSE, The Hong Kong Polytechnic University) for his help in processing and submitting our samples for proteomics analysis. We thank Yingying Li (SCELSE, NTU LKCMedicine) for her guidance in RT-PCR experiments.

Funding Information:
This research was supported by the National Research Foundation and the Singapore Ministry of Education under its Research Centre of Excellence Programme, and by the Ministry of Education Academic Research Fund Tier 2 grant (MOE2016-T2-1-104) (to S.-S.C.). M.G., S.-S.C., L.Y., L.Z.W.T., and Z.H. have filed an international patent application (PCT/SG2016/050436, filed 6th September 2016) and granted a US patent (US 10,258,640 B2, dated 16th April 2019) on the work described in this manuscript.

Publisher Copyright:
© 2023 Elsevier Ltd

    Research areas

  • Auranofin, Colistin, Gold(I), Infection, Motility, Pseudomonas aeruginosa, Quorum sensing, Synergy, Thiophilic, Virulence

ID: 340025398