Antibacterial activity and mechanism of mangosteen extract garcinone D against Bacillus cereus

This study systematically investigated the antibacterial activity and underlying mechanism of garcinone D, a xanthone isolated and purified from mangosteen, against B. cereus. The results demonstrated that garcinone D exhibited significant inhibitory activity, with a MIC₉₀ of 3.12 μg/mL, which is markedly lower than that of the commercial preservative ε-polylysine (MIC₉₀ = 25 μg/mL). Furthermore, garcinone D produced a larger inhibition zone diameter. In a rice preservation model, garcinone D effectively reduced the total bacterial count. Mechanistic studies revealed that garcinone D exerts its antibacterial activity primarily by disrupting cell membrane integrity. Specifically, it increased membrane permeability, leading to the leakage of intracellular components such as nucleic acids and proteins. PI staining further confirmed the loss of membrane integrity. Additionally, garcinone D induces ROS accumulation accompanied by a significant increase in MDA content, indicating that membrane lipid peroxidation exacerbates membrane damage. RNA-seq transcriptomic analysis and KEGG pathway enrichment indicated that DEGs were significantly enriched in categories related to cell envelope and transport, particularly the ABC transporter pathway, as well as in central metabolic pathways and QS/virulence-related pathways. Subsequent experiments confirmed that garcinone D markedly reduced intracellular ATP levels and inhibited the hemolytic activity of B. cereus toxins. RT-qPCR validated the expression changes of genes related to these functions. In the 5000 mg/kg acute toxicity test, garcinone D did not cause any deaths or adverse effects on general behavior and body weight, indicating good tolerance in mice under this exposure condition and providing acute safety data for the preliminary application of garcinone D. In conclusion, garcinone D will be developed into a highly effective and safe natural antibacterial agent. Which has broad application prospects in controlling food contamination and relating foodborne diseases caused by B. cereus.