Magnolol as an Antibacterial Agent Against Drug-resistant Bacteria Targeting Filamentous Temperature-sensitive Mutant Z

The emergence of multiple drug-resistant bacteria poses critical health threats worldwide. It is urgently needed to develop potent and safe antibacterial agents with novel bactericidal mechanisms to treat these infections. In this study, magnolol was identified as a potential bacterial cell division inhibitor by a cell-based screening approach. This compound showed good antibacterial activity against a number of Gram-positive pathogens (minimum inhibitory concentration 8-16 µg/mL) including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Further results obtained from biochemical experiments demonstrated that magnolol could markedly disrupt GTPase activity and filamentous temperature-sensitive mutant Z (FtsZ) polymerization, consistent with the impediment to cell division in the bacteria tested. The in vivo antibacterial activity of magnolol was evaluated with a Galleria mellonella larvae model. The results showed that magnolol significantly increased the survival rate of larvae infected with methicillin-resistant S. aureus. The interaction pattern of magnolol with FtsZ was investigated through molecular docking. The finding may offer meaningful insights into the mechanism of action of the compound. The results point to magnolol as a promising antimicrobial compound that inhibits cell division by affecting FtsZ polymerization and has the potential to be developed into an effective antimicrobial drug by further structure modification.