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...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Online Access: | https://hdl.handle.net/10356/168713 |
| _version_ | 1824456371263766528 |
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| author | Zhang, Yingdan Chew, Alvin Bing Liang Wang, Jing Yuan, Mingjun Yam, Joey Kuok Hoong Luo, Dahai Yang, Liang |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Zhang, Yingdan Chew, Alvin Bing Liang Wang, Jing Yuan, Mingjun Yam, Joey Kuok Hoong Luo, Dahai Yang, Liang |
| author_sort | Zhang, Yingdan |
| collection | NTU |
| 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 | 2025-02-19T03:53:02Z |
| format | Journal Article |
| id | ntu-10356/168713 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:53:02Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1687132023-06-18T15:39:08Z Structural basis for the inhibitory mechanism of auranofin and gold(I) analogues against Pseudomonas aeruginosa global virulence factor regulator Vfr Zhang, Yingdan Chew, Alvin Bing Liang Wang, Jing Yuan, Mingjun Yam, Joey Kuok Hoong Luo, Dahai Yang, Liang Lee Kong Chian School of Medicine (LKCMedicine) Singapore Centre for Environmental Life Sciences and Engineering (SCELSE) NTU Institute of Structural Biology Science::Medicine Antimicrobial Virulence 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. Ministry of Education (MOE) Published version This research is supported by the Singapore Ministry of Education under its Singapore Ministry of Education Academic Research Fund Tier 1 (2018-T1-002-010) and Tier 2 (2016-T2-2-097) to D.L.; Nanyang Presidential Graduate Scholarship to B.L.A.C.; the Guangdong Natural Science Foundation for Distinguished Young Scholar [2020B1515020003]; the National Key Research and Development Program of China (2022YFC2304700); the National Natural Science Foundation of China (32270196 and 32200155); the Guangdong Basic and Applied Basic Research Foundation [2019A1515110640]; and the Shenzhen Overseas High-level Talent Team (KQTD20200909113758004). 2023-06-16T02:11:49Z 2023-06-16T02:11:49Z 2023 Journal Article Zhang, Y., Chew, A. B. L., Wang, J., Yuan, M., Yam, J. K. H., Luo, D. & Yang, L. (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. https://dx.doi.org/10.1016/j.csbj.2023.03.013 2001-0370 https://hdl.handle.net/10356/168713 10.1016/j.csbj.2023.03.013 37007650 2-s2.0-85150854721 21 2137 2146 en 2018-T1-002-010 2016-T2-2-097 Computational and Structural Biotechnology Journal © 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://creativecommons.org/licenses/by/4.0/). application/pdf |
| spellingShingle | Science::Medicine Antimicrobial Virulence Zhang, Yingdan Chew, Alvin Bing Liang Wang, Jing Yuan, Mingjun Yam, Joey Kuok Hoong Luo, Dahai Yang, Liang Structural basis for the inhibitory mechanism of auranofin and gold(I) analogues against Pseudomonas aeruginosa global virulence factor regulator Vfr |
| 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 | Science::Medicine Antimicrobial Virulence |
| url | https://hdl.handle.net/10356/168713 |
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