Gold(I) selenium N-heterocyclic carbene complexes as potent antibacterial agents against multidrug-resistant gram-negative bacteria via inhibiting thioredoxin reductase
Multidrug-resistant (MDR) Gram-negative bacteria have become a global threat to human life and health, and novel antibiotics are urgently needed. The thioredoxin (Trx) system can be used as an antibacterial target to combat MDR bacteria. Here, we found that two active gold(I) selenium N-heterocyclic...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231723000228 |
| _version_ | 1811168454641713152 |
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| author | Xiuli Chen Shibo Sun Sheng Huang Han Yang Qing Ye Lin Lv Yanshan Liang Jinjun Shan Jianqiang Xu Wukun Liu Tonghui Ma |
| author_facet | Xiuli Chen Shibo Sun Sheng Huang Han Yang Qing Ye Lin Lv Yanshan Liang Jinjun Shan Jianqiang Xu Wukun Liu Tonghui Ma |
| author_sort | Xiuli Chen |
| collection | DOAJ |
| description | Multidrug-resistant (MDR) Gram-negative bacteria have become a global threat to human life and health, and novel antibiotics are urgently needed. The thioredoxin (Trx) system can be used as an antibacterial target to combat MDR bacteria. Here, we found that two active gold(I) selenium N-heterocyclic carbene complexes H7 and H8 show more promising antibacterial effects against MDR bacteria than auranofin. Both H7 and H8 irreversibly inhibit the bacterial TrxR activity via targeting the redox-active motif, abolishing the capacity of TrxR to quench reactive oxygen species (ROS) and finally leading to oxidative stress. The increased cellular superoxide radical levels impact a variety of functions necessary for bacterial survival, such as cellular redox balance, cell membrane integrity, amino acid metabolism, and lipid peroxidation. In vivo data present much better antibacterial activity of H7 and H8 than auranofin, promoting the wound healing and prolonging the survival time of Carbapenem-resistant Acinetobacter baumannii (CRAB) induced peritonitis. Most notably in this study, we revealed the influence of gold(I) complexes on both the Trx system and the cellular metabolic states to better understand their killing mechanism and to support further antibacterial drug design. |
| first_indexed | 2024-04-10T16:26:35Z |
| format | Article |
| id | doaj.art-2a9c13647a1e4c1d95a21c012835a7df |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-10T16:26:35Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-2a9c13647a1e4c1d95a21c012835a7df2023-02-09T04:14:05ZengElsevierRedox Biology2213-23172023-04-0160102621Gold(I) selenium N-heterocyclic carbene complexes as potent antibacterial agents against multidrug-resistant gram-negative bacteria via inhibiting thioredoxin reductaseXiuli Chen0Shibo Sun1Sheng Huang2Han Yang3Qing Ye4Lin Lv5Yanshan Liang6Jinjun Shan7Jianqiang Xu8Wukun Liu9Tonghui Ma10School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, ChinaSchool of Life and Pharmaceutical Sciences (LPS) & Panjin Institute of Industrial Technology (PIIT), Dalian University of Technology, Panjin, 124221, ChinaSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, ChinaSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, ChinaSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, ChinaSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, ChinaSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, ChinaMedical Metabolomics Center, Nanjing University of Chinese Medicine, Nanjing, 210023, ChinaSchool of Life and Pharmaceutical Sciences (LPS) & Panjin Institute of Industrial Technology (PIIT), Dalian University of Technology, Panjin, 124221, China; Corresponding author.School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Corresponding author.School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Corresponding author.Multidrug-resistant (MDR) Gram-negative bacteria have become a global threat to human life and health, and novel antibiotics are urgently needed. The thioredoxin (Trx) system can be used as an antibacterial target to combat MDR bacteria. Here, we found that two active gold(I) selenium N-heterocyclic carbene complexes H7 and H8 show more promising antibacterial effects against MDR bacteria than auranofin. Both H7 and H8 irreversibly inhibit the bacterial TrxR activity via targeting the redox-active motif, abolishing the capacity of TrxR to quench reactive oxygen species (ROS) and finally leading to oxidative stress. The increased cellular superoxide radical levels impact a variety of functions necessary for bacterial survival, such as cellular redox balance, cell membrane integrity, amino acid metabolism, and lipid peroxidation. In vivo data present much better antibacterial activity of H7 and H8 than auranofin, promoting the wound healing and prolonging the survival time of Carbapenem-resistant Acinetobacter baumannii (CRAB) induced peritonitis. Most notably in this study, we revealed the influence of gold(I) complexes on both the Trx system and the cellular metabolic states to better understand their killing mechanism and to support further antibacterial drug design.http://www.sciencedirect.com/science/article/pii/S2213231723000228N-heterocyclic carbineGold(I) complexesThioredoxin reductaseReactive oxygen speciesDrug-resistant bacteria |
| spellingShingle | Xiuli Chen Shibo Sun Sheng Huang Han Yang Qing Ye Lin Lv Yanshan Liang Jinjun Shan Jianqiang Xu Wukun Liu Tonghui Ma Gold(I) selenium N-heterocyclic carbene complexes as potent antibacterial agents against multidrug-resistant gram-negative bacteria via inhibiting thioredoxin reductase Redox Biology N-heterocyclic carbine Gold(I) complexes Thioredoxin reductase Reactive oxygen species Drug-resistant bacteria |
| title | Gold(I) selenium N-heterocyclic carbene complexes as potent antibacterial agents against multidrug-resistant gram-negative bacteria via inhibiting thioredoxin reductase |
| title_full | Gold(I) selenium N-heterocyclic carbene complexes as potent antibacterial agents against multidrug-resistant gram-negative bacteria via inhibiting thioredoxin reductase |
| title_fullStr | Gold(I) selenium N-heterocyclic carbene complexes as potent antibacterial agents against multidrug-resistant gram-negative bacteria via inhibiting thioredoxin reductase |
| title_full_unstemmed | Gold(I) selenium N-heterocyclic carbene complexes as potent antibacterial agents against multidrug-resistant gram-negative bacteria via inhibiting thioredoxin reductase |
| title_short | Gold(I) selenium N-heterocyclic carbene complexes as potent antibacterial agents against multidrug-resistant gram-negative bacteria via inhibiting thioredoxin reductase |
| title_sort | gold i selenium n heterocyclic carbene complexes as potent antibacterial agents against multidrug resistant gram negative bacteria via inhibiting thioredoxin reductase |
| topic | N-heterocyclic carbine Gold(I) complexes Thioredoxin reductase Reactive oxygen species Drug-resistant bacteria |
| url | http://www.sciencedirect.com/science/article/pii/S2213231723000228 |
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