2. Academic Validation
  3. Dronedarone Enhances the Antibacterial Activity of Polymyxin B and Inhibits the Quorum Sensing System by Interacting with LuxS

Dronedarone Enhances the Antibacterial Activity of Polymyxin B and Inhibits the Quorum Sensing System by Interacting with LuxS

  • ACS Infect Dis. 2024 Feb 5. doi: 10.1021/acsinfecdis.3c00591.
Ruiqin Cui 1 2,  Jinyong Zhang 3,  Xiaodi Liu 4,  Chunxia Hu 1 2,  Fan Zhou 1 2,  Min Zhang 1,  Xiao Wang 5,  Quanming Zou 3,  Wei Huang 2 6
Affiliations

Affiliations

  • 1 Antimicrobial Drug Screening Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, China.
  • 2 Department of Medical Laboratory, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong China.
  • 3 National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
  • 4 Department of Infectious Diseases, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong China.
  • 5 Department of Pharmacy, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong China.
  • 6 Division of Hepatobiliary and Pancreas Surgery, Department of General Surgery, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong China.
PMID: 38317424 DOI: 10.1021/acsinfecdis.3c00591
Abstract

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.

Keywords

AI-2; Klebsiella pneumoniae; LuxS; dronedarone; polymyxin B; quorum sensing system.

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