Disruption of Bacterial Thiol-Dependent Redox Homeostasis by Magnolol and Honokiol as an Antibacterial Strategy
Yanfang Ouyang,
Xuewen Tang,
Ying Zhao,
Xin Zuo,
Xiaoyuan Ren,
Jun Wang,
Lili Zou,
Jun Lu
Affiliations
Yanfang Ouyang
Engineering Research Center of Coptis Development and Utilization/Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education (Southwest University), College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
Xuewen Tang
Engineering Research Center of Coptis Development and Utilization/Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education (Southwest University), College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
Ying Zhao
Engineering Research Center of Coptis Development and Utilization/Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education (Southwest University), College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
Xin Zuo
Engineering Research Center of Coptis Development and Utilization/Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education (Southwest University), College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
Xiaoyuan Ren
Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden
Jun Wang
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang 443002, China
Lili Zou
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang 443002, China
Jun Lu
Engineering Research Center of Coptis Development and Utilization/Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education (Southwest University), College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
Some traditional Chinese medicines (TCMs) possess various redox-regulation properties, but whether the redox regulation contributes to antibacterial mechanisms is not known. Here, ginger juice processed Magnoliae officinalis cortex (GMOC) was found to show strong antibacterial activities against some Gram-positive bacteria, but not Gram-negative bacteria including E. coli, while the redox-related transcription factor oxyR deficient E. coli mutant was sensitive to GMOC. In addition, GMOC and its main ingredients, magnolol and honokiol, exhibited inhibitory effects on the bacterial thioredoxin (Trx) system, a major thiol-dependent disulfide reductase system in bacteria. The effects of magnolol and honokiol on cellular redox homeostasis were further verified by elevation of the intracellular ROS levels. The therapeutic efficacies of GMOC, magnolol and honokiol were further verified in S. aureus-caused mild and acute peritonitis mouse models. Treatments with GMOC, magnolol and honokiol significantly reduced the bacterial load, and effectively protected the mice from S. aureus-caused peritonitis infections. Meanwhile, magnolol and honokiol produced synergistic effects when used in combination with several classic antibiotics. These results strongly suggest that some TCMs may exert their therapeutic effects via targeting the bacterial thiol-dependent redox system.
