Dronedarone Enhances the Antibacterial Activity of Polymyxin B and Inhibits the Quorum Sensing System by Interacting with LuxS.
Ruiqin CuiJinyong ZhangXiaodi LiuChunxia HuFan ZhouMin ZhangXiao WangQuanming ZouWei HuangPublished in: ACS infectious diseases (2024)
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.
Keyphrases
- candida albicans
- biofilm formation
- klebsiella pneumoniae
- silver nanoparticles
- multidrug resistant
- heavy metals
- escherichia coli
- gram negative
- artificial intelligence
- binding protein
- pseudomonas aeruginosa
- risk assessment
- transcription factor
- angiotensin ii
- staphylococcus aureus
- anti inflammatory
- deep learning
- cystic fibrosis
- emergency department