Disruption of Bacterial Thiol-Dependent Redox Homeostasis by Magnolol and Honokiol as an Antibacterial Strategy

Abstract

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.