Research finds prenylated flavonoids improve bactericidal activity against methicillin-resistant staphylococcus aureus, suggesting new strategies to tackle bacterial persistence.
Antibiotic resistance and bacterial persistence threaten global health, with methicillin-resistant Staphylococcus aureus (MRSA) being a particularly challenging pathogen. In this work, 3'-C-geranylphloretin (GP), a prenylated phenolic compound, showed better bactericidal activity against dormant MRSA cells than vancomycin. It significantly decreased bacterial loads, lung index, and improved pathological deterioration mediated by MRSA infection in vivo, and showed good safety to normal mice. Bacterial clearance was directly observed by two-photon excitation microscopy. GP disrupted bacterial persistence by targeting the transcriptional regulator FarR, which activated fatty acid and energy metabolism. Besides, GP-induced cell membrane disruption and apoptosis-like cell death in MRSA are caused by chromosomal condensation, reactive oxygen species (ROS) accumulation, and caspase-3/7 activation. Our research holds potential for anti-persister drug development.
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Sheng et al. (2025) studied this question.
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