Computational and Biological Evaluation of <i>β</i>-Adrenoreceptor Blockers as Promising Bacterial Anti-Virulence Agents
Bacterial resistance to antibiotics is an increasing public health threat as it has the potential to affect people at any stage of life, as well as veterinary. Various approaches have been proposed to counteract the bacterial resistance development. Tackling bacterial virulence is one of the most pr...
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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/2/110 |
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| author | Ahmad J. Almalki Tarek S. Ibrahim Sameh S. Elhady Wael A. H. Hegazy Khaled M. Darwish |
| author_facet | Ahmad J. Almalki Tarek S. Ibrahim Sameh S. Elhady Wael A. H. Hegazy Khaled M. Darwish |
| author_sort | Ahmad J. Almalki |
| collection | DOAJ |
| description | Bacterial resistance to antibiotics is an increasing public health threat as it has the potential to affect people at any stage of life, as well as veterinary. Various approaches have been proposed to counteract the bacterial resistance development. Tackling bacterial virulence is one of the most promising approaches that confer several merits. The bacterial virulence is mainly regulated by a communication system known as quorum sensing (QS) system. Meanwhile, bacteria can sense the adrenergic hormones and eavesdrops on the host cells to establish their infection, adrenergic hormones were shown to enhance the bacterial virulence. In this study, <i>β</i>-adrenoreceptor blockers were proposed not only to stop bacterial espionage on our cells but also as inhibitors to the bacterial QS systems. In this context, a detailed in silico study has been conducted to evaluate the affinities of twenty-two <i>β</i>-blockers to compete on different structural QS receptors. Among the best docked and thermodynamically stable <i>β</i>-blockers; atenolol, esmolol, and metoprolol were subjected to further in vitro and in vivo investigation to evaluate their anti-QS activities against <i>Chromobacterium violaceum</i>, <i>Pseudomonas aeruginosa</i> and <i>Salmonella</i> <i>typhimurium</i>. The three tested <i>β</i>-blockers decreased the production of QS-controlled <i>C. violaceum</i>, and the formation of biofilm by <i>P. aeruginosa</i> and <i>S. typhimurium</i>. Additionally, the tested <i>β</i>-blockers down-regulated the <i>P. aeruginosa</i> QS-encoding genes and <i>S.</i> <i>typhimurium</i> sensor kinase encoding genes. Furthermore, metoprolol protected mice against <i>P. aeruginosa</i> and <i>S.</i> <i>typhimurium</i>. Conclusively, these investigated <i>β</i>-blockers are promising anti-virulence agents antagonizing adrenergic hormones induced virulence, preventing bacterial espionage, and blocking bacterial QS systems. |
| first_indexed | 2024-03-09T21:16:04Z |
| format | Article |
| id | doaj.art-8e44a09a877e465dabea9d5a7b8d1d2a |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T21:16:04Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-8e44a09a877e465dabea9d5a7b8d1d2a2023-11-23T21:33:11ZengMDPI AGPharmaceuticals1424-82472022-01-0115211010.3390/ph15020110Computational and Biological Evaluation of <i>β</i>-Adrenoreceptor Blockers as Promising Bacterial Anti-Virulence AgentsAhmad J. Almalki0Tarek S. Ibrahim1Sameh S. Elhady2Wael A. H. Hegazy3Khaled M. Darwish4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Medicinal Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptBacterial resistance to antibiotics is an increasing public health threat as it has the potential to affect people at any stage of life, as well as veterinary. Various approaches have been proposed to counteract the bacterial resistance development. Tackling bacterial virulence is one of the most promising approaches that confer several merits. The bacterial virulence is mainly regulated by a communication system known as quorum sensing (QS) system. Meanwhile, bacteria can sense the adrenergic hormones and eavesdrops on the host cells to establish their infection, adrenergic hormones were shown to enhance the bacterial virulence. In this study, <i>β</i>-adrenoreceptor blockers were proposed not only to stop bacterial espionage on our cells but also as inhibitors to the bacterial QS systems. In this context, a detailed in silico study has been conducted to evaluate the affinities of twenty-two <i>β</i>-blockers to compete on different structural QS receptors. Among the best docked and thermodynamically stable <i>β</i>-blockers; atenolol, esmolol, and metoprolol were subjected to further in vitro and in vivo investigation to evaluate their anti-QS activities against <i>Chromobacterium violaceum</i>, <i>Pseudomonas aeruginosa</i> and <i>Salmonella</i> <i>typhimurium</i>. The three tested <i>β</i>-blockers decreased the production of QS-controlled <i>C. violaceum</i>, and the formation of biofilm by <i>P. aeruginosa</i> and <i>S. typhimurium</i>. Additionally, the tested <i>β</i>-blockers down-regulated the <i>P. aeruginosa</i> QS-encoding genes and <i>S.</i> <i>typhimurium</i> sensor kinase encoding genes. Furthermore, metoprolol protected mice against <i>P. aeruginosa</i> and <i>S.</i> <i>typhimurium</i>. Conclusively, these investigated <i>β</i>-blockers are promising anti-virulence agents antagonizing adrenergic hormones induced virulence, preventing bacterial espionage, and blocking bacterial QS systems.https://www.mdpi.com/1424-8247/15/2/110bacterial virulence<i>β</i>-adrenergic blockersquorum sensingadrenergic hormonesbacterial espionage<i>Pseudomonas aeruginosa</i> |
| spellingShingle | Ahmad J. Almalki Tarek S. Ibrahim Sameh S. Elhady Wael A. H. Hegazy Khaled M. Darwish Computational and Biological Evaluation of <i>β</i>-Adrenoreceptor Blockers as Promising Bacterial Anti-Virulence Agents Pharmaceuticals bacterial virulence <i>β</i>-adrenergic blockers quorum sensing adrenergic hormones bacterial espionage <i>Pseudomonas aeruginosa</i> |
| title | Computational and Biological Evaluation of <i>β</i>-Adrenoreceptor Blockers as Promising Bacterial Anti-Virulence Agents |
| title_full | Computational and Biological Evaluation of <i>β</i>-Adrenoreceptor Blockers as Promising Bacterial Anti-Virulence Agents |
| title_fullStr | Computational and Biological Evaluation of <i>β</i>-Adrenoreceptor Blockers as Promising Bacterial Anti-Virulence Agents |
| title_full_unstemmed | Computational and Biological Evaluation of <i>β</i>-Adrenoreceptor Blockers as Promising Bacterial Anti-Virulence Agents |
| title_short | Computational and Biological Evaluation of <i>β</i>-Adrenoreceptor Blockers as Promising Bacterial Anti-Virulence Agents |
| title_sort | computational and biological evaluation of i β i adrenoreceptor blockers as promising bacterial anti virulence agents |
| topic | bacterial virulence <i>β</i>-adrenergic blockers quorum sensing adrenergic hormones bacterial espionage <i>Pseudomonas aeruginosa</i> |
| url | https://www.mdpi.com/1424-8247/15/2/110 |
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