Structural basis for the inhibitory mechanism of auranofin and gold(I) analogues against Pseudomonas aeruginosa global virulence factor regulator Vfr
Pseudomonas aeruginosa is a leading cause of hospital-acquired infections. Treatment of P. aeruginosa infections is difficult given its multiple virulence mechanisms, intrinsic antibiotic resistance mechanisms, and biofilm-forming ability. Auranofin, an approved oral gold compound for rheumatoid art...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Computational and Structural Biotechnology Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037023001125 |
| _version_ | 1827577707249008640 |
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| author | Yingdan Zhang Bing Liang Alvin Chew Jing Wang Mingjun Yuan Joey Kuok Hoong Yam Dahai Luo Liang Yang |
| author_facet | Yingdan Zhang Bing Liang Alvin Chew Jing Wang Mingjun Yuan Joey Kuok Hoong Yam Dahai Luo Liang Yang |
| author_sort | Yingdan Zhang |
| collection | DOAJ |
| description | Pseudomonas aeruginosa is a leading cause of hospital-acquired infections. Treatment of P. aeruginosa infections 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 inhibitory mechanism of auranofin and gold(I) analogues to Vfr through structural, biophysical, and phenotypic inhibition studies. This work suggests that auranofin and gold(I) analogues have potential to be developed as anti-virulence drugs against P. aeruginosa. |
| first_indexed | 2024-03-08T21:31:42Z |
| format | Article |
| id | doaj.art-e3f91a7eb7774cd58cda1022d7470939 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-03-08T21:31:42Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-e3f91a7eb7774cd58cda1022d74709392023-12-21T07:31:13ZengElsevierComputational and Structural Biotechnology Journal2001-03702023-01-012121372146Structural basis for the inhibitory mechanism of auranofin and gold(I) analogues against Pseudomonas aeruginosa global virulence factor regulator VfrYingdan Zhang0Bing Liang Alvin Chew1Jing Wang2Mingjun Yuan3Joey Kuok Hoong Yam4Dahai Luo5Liang Yang6Shenzhen Third People’s Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Shenzhen 518112, China; School of Medicine, Southern University of Science and Technology, Shenzhen 518055, Guangdong, ChinaLee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921; NTU Institute of Structural Biology, Nanyang Technological University, EMB 06-01, 59 Nanyang Drive, 636921, Singapore; Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, SingaporeSchool of Medicine, Southern University of Science and Technology, Shenzhen 518055, Guangdong, ChinaSingapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore; Guanghua Science and Technology Research Institute (Guangdong) Co., Ltd, ChinaSingapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, SingaporeLee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921; NTU Institute of Structural Biology, Nanyang Technological University, EMB 06-01, 59 Nanyang Drive, 636921, Singapore; Corresponding author at: Lee Kong Chian School of Medicine, Nanyang Technological University, 636921, Singapore.Shenzhen Third People’s Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Shenzhen 518112, China; School of Medicine, Southern University of Science and Technology, Shenzhen 518055, Guangdong, China; Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore; Corresponding author at: Shenzhen Third People’s Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Shenzhen 518112, China.Pseudomonas aeruginosa is a leading cause of hospital-acquired infections. Treatment of P. aeruginosa infections 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 inhibitory mechanism of auranofin and gold(I) analogues to Vfr through structural, biophysical, and phenotypic inhibition studies. This work suggests that auranofin and gold(I) analogues have potential to be developed as anti-virulence drugs against P. aeruginosa.http://www.sciencedirect.com/science/article/pii/S2001037023001125AntimicrobialVirulencePseudomonasVfrAuranofinGold(I) analogues |
| spellingShingle | Yingdan Zhang Bing Liang Alvin Chew Jing Wang Mingjun Yuan Joey Kuok Hoong Yam Dahai Luo Liang Yang 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 Antimicrobial Virulence Pseudomonas Vfr Auranofin Gold(I) analogues |
| title | Structural basis for the inhibitory mechanism of auranofin and gold(I) analogues against Pseudomonas aeruginosa global virulence factor regulator Vfr |
| title_full | Structural basis for the inhibitory mechanism of auranofin and gold(I) analogues against Pseudomonas aeruginosa global virulence factor regulator Vfr |
| title_fullStr | Structural basis for the inhibitory mechanism of auranofin and gold(I) analogues against Pseudomonas aeruginosa global virulence factor regulator Vfr |
| title_full_unstemmed | Structural basis for the inhibitory mechanism of auranofin and gold(I) analogues against Pseudomonas aeruginosa global virulence factor regulator Vfr |
| title_short | Structural basis for the inhibitory mechanism of auranofin and gold(I) analogues against Pseudomonas aeruginosa global virulence factor regulator Vfr |
| title_sort | structural basis for the inhibitory mechanism of auranofin and gold i analogues against pseudomonas aeruginosa global virulence factor regulator vfr |
| topic | Antimicrobial Virulence Pseudomonas Vfr Auranofin Gold(I) analogues |
| url | http://www.sciencedirect.com/science/article/pii/S2001037023001125 |
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