Dronedarone Enhances the Antibacterial Activity of Polymyxin B and Inhibits the Quorum Sensing System by Interacting with LuxS
Quorum sensing (QS) is considered an appealing target for interference with bacterial infections. β-Adrenergic blockers are promising anti-QS agents but do not have antibacterial activity. We assessed the potential ability of adrenergic receptor inhibitors to enhance the antibacterial activity of polymyxin B (PB) against Klebsiella pneumoniae and determined that dronedarone has the most potent activity both in vitro and in vivo. We found that dronedarone increases the thermal stability of LuxS, decreases the production of AI-2, and affects the biofilm formation of K. pneumoniae. We also identified the direct binding of dronedarone to LuxS. However, the mechanism by which dronedarone enhances the antibacterial activity of PB has not been elucidated and is worthy of further exploration. Our study provides a basis for the future development of drug combination regimens.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
ACS infectious diseases - 10(2024), 3 vom: 08. März, Seite 961-970 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cui, Ruiqin [VerfasserIn] |
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| Links: |
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| Themen: |
AI-2 |
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| Anmerkungen: |
Date Completed 11.03.2024 Date Revised 11.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acsinfecdis.3c00591 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368066843 |
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| 520 | |a Quorum sensing (QS) is considered an appealing target for interference with bacterial infections. β-Adrenergic blockers are promising anti-QS agents but do not have antibacterial activity. We assessed the potential ability of adrenergic receptor inhibitors to enhance the antibacterial activity of polymyxin B (PB) against Klebsiella pneumoniae and determined that dronedarone has the most potent activity both in vitro and in vivo. We found that dronedarone increases the thermal stability of LuxS, decreases the production of AI-2, and affects the biofilm formation of K. pneumoniae. We also identified the direct binding of dronedarone to LuxS. However, the mechanism by which dronedarone enhances the antibacterial activity of PB has not been elucidated and is worthy of further exploration. Our study provides a basis for the future development of drug combination regimens | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AI-2 | |
| 650 | 4 | |a Klebsiella pneumoniae | |
| 650 | 4 | |a LuxS | |
| 650 | 4 | |a dronedarone | |
| 650 | 4 | |a polymyxin B | |
| 650 | 4 | |a quorum sensing system | |
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| 650 | 7 | |a Dronedarone |2 NLM | |
| 650 | 7 | |a JQZ1L091Y2 |2 NLM | |
| 650 | 7 | |a Bacterial Proteins |2 NLM | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 700 | 1 | |a Zhang, Jinyong |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiaodi |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Chunxia |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Zou, Quanming |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Wei |e verfasserin |4 aut | |
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