Structural basis for the inhibitory mechanism of auranofin and gold(I) analogues against Pseudomonas aeruginosa global virulence factor regulator Vfr

Zhang, Yingdan1,2; Chew, Bing Liang Alvin3,4,5; Wang, Jing2; Yuan, Mingjun5,6; Yam, Joey Kuok Hoong5; Luo, Dahai3,4; Yang, Liang1,2,5

2023

10.1016/j.csbj.2023.03.013

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL   影响因子和分区

2001-0370

Pseudomonas aeruginosa is a leading cause of hospital-acquired infections. Treatment of P. aeruginosa in-fections is difficult given its multiple virulence mechanisms, intrinsic antibiotic resistance mechanisms, and biofilm-forming ability. Auranofin, an approved oral gold compound for rheumatoid arthritis treatment, was recently reported to inhibit the growth of multiple bacterial species. Here, we identify P. aeruginosa's global virulence factor regulator Vfr as one target of auranofin. We report the mechanistic insights into the in-hibitory mechanism of auranofin and gold(I) analogues to Vfr through structural, biophysical, and pheno-typic inhibition studies. This work suggests that auranofin and gold(I) analogues have potential to be developed as anti-virulence drugs against P. aeruginosa.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY license (http://creative-commons.org/licenses/by/4.0/).

Antimicrobial Virulence Pseudomonas Vfr Auranofin Gold(I) analogues

SCI ; EI

英语

第一 ; 通讯

Singapore Ministry of Education under its Singapore Ministry of Education Academic Research Fund Tier 1 and Tier 2["2018-T1-002-010","2016-T2-2-097"] ; Guangdong Natural Science Foundation for Distinguished Young Scholar[2020B1515020003] ; National Key Research and Development Program of China[2022YFC2304700] ; National Natural Science Foundation of China["32270196","32200155"] ; Guangdong Basic and Applied Basic Research Foundation[2019A1515110640] ; Shenzhen Overseas High-level Talent Team[KQTD20200909113758004]

Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology

Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology

WOS:000959891400001

ELSEVIER

20231313806794

Bacteria ; Diseases

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Affiliated Hosp 2, Natl Clin Res Ctr Infect Dis, Shenzhen 518112, Peoples R China
2.Southern Univ Sci & Technol, Sch Med, Shenzhen 518055, Guangdong, Peoples R China
3.Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 636921, Singapore
4.Nanyang Technol Univ, NTU Inst Struct Biol, EMB 06-01,59 Nanyang Dr, Singapore 636921, Singapore
5.Nanyang Technol Univ, Singapore Ctr Environm Life Sci Engn SCELSE, Singapore, Singapore
6.Guanghua Sci & Technol Res Inst Guangdong Co Ltd, Guangzhou, Peoples R China

Zhang, Yingdan,Chew, Bing Liang Alvin,Wang, Jing,et al. Structural basis for the inhibitory mechanism of auranofin and gold(I) analogues against Pseudomonas aeruginosa global virulence factor regulator Vfr[J]. COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL,2023,21:2137-2146.

Zhang, Yingdan.,Chew, Bing Liang Alvin.,Wang, Jing.,Yuan, Mingjun.,Yam, Joey Kuok Hoong.,...&Yang, Liang.(2023).Structural basis for the inhibitory mechanism of auranofin and gold(I) analogues against Pseudomonas aeruginosa global virulence factor regulator Vfr.COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL,21,2137-2146.

Zhang, Yingdan,et al."Structural basis for the inhibitory mechanism of auranofin and gold(I) analogues against Pseudomonas aeruginosa global virulence factor regulator Vfr".COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL 21(2023):2137-2146.