Auranofin inhibits virulence pathways in Pseudomonas aeruginosa

Yam，Joey Kuok Hoong1; Tan，Leon Zhen Wei1,2; Hong，Ziyan1; Salido，May Margarette Santillan1; Woo，Bau Yi1,2; Yong，Adeline Mei Hui1; Tan，Casandra Ai Zhu1,3; Li，Sam Fong Yau1; Yang，Liang1,3,5; Givskov，Michael1,4; Chng，Shu Sin1,2

2023-02-01

10.1016/j.bmc.2023.117167

Bioorganic and Medicinal Chemistry   影响因子和分区

0968-0896

1464-3391

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.

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

SCI

英语

其他

Ministry of Education Academic Research Fund Tier 2 grant[MOE2016-T2-1-104]

Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry

Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Chemistry, Organic

WOS:000963176000001

PERGAMON-ELSEVIER SCIENCE LTD

CHEMISTRY

2-s2.0-85146648255

Scopus

1.Singapore Center for Environmental Life Sciences Engineering (SCELSE),Nanyang Technological University,Singapore,637551,Singapore
2.Department of Chemistry,National University of Singapore,Singapore,117543,Singapore
3.School of Biological Sciences,Nanyang Technological University,Singapore,639798,Singapore
4.Costerton Biofilm Center,Department of Immunology and Microbiology,University of Copenhagen,DK- 2200,Denmark
5.School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong Province,518055,China

Yam，Joey Kuok Hoong,Tan，Leon Zhen Wei,Hong，Ziyan,et al. Auranofin inhibits virulence pathways in Pseudomonas aeruginosa[J]. Bioorganic and Medicinal Chemistry,2023,79.

Yam，Joey Kuok Hoong.,Tan，Leon Zhen Wei.,Hong，Ziyan.,Salido，May Margarette Santillan.,Woo，Bau Yi.,...&Chng，Shu Sin.(2023).Auranofin inhibits virulence pathways in Pseudomonas aeruginosa.Bioorganic and Medicinal Chemistry,79.

Yam，Joey Kuok Hoong,et al."Auranofin inhibits virulence pathways in Pseudomonas aeruginosa".Bioorganic and Medicinal Chemistry 79(2023).