Anthraquinones derived from soil actinomycetes combat multidrug-resistant Staphylococcus aureus

The global spread of multidrug-resistant Staphylococcus aureus (MRSA) poses serious threats to public health and food safety. In this study, the antibacterial potential of the anthraquinone compound 13394-2, derived from soil actinomycetes, was systematically evaluated. In vitro, 13394-2 exhibited potent activity (MIC as low as 0.25 μg/mL), rapid bactericidal effects, biofilm clearance, and concentration-dependent killing. Mechanistic studies revealed that membrane disruption, ROS accumulation, and ATP depletion are key bactericidal pathways leading to metabolic collapse. Transcriptomic, computational analyses and biophysical experiments revealed significant interference with protein, energy, and fatty acid metabolism, with FabF identified as a potential target. Toxicity assessments confirmed low cytotoxicity and good in vivo safety. In animal infection models, 13394-2 improved survival, reduced bacterial burden and tissue damage, and promoted wound healing. It also effectively eliminated drug-resistant S. aureus in simulated food and surface contamination models. These findings support the potential of anthraquinones as potential antibiotics against drug-resistant infections and environmental contamination.