To investigate the antibacterial activity, mechanism of action, and wound healing-promoting effect of Artemisia argyi essential oil (AAEO) against carbapenem-resistant Escherichia coli CREO-76. The minimum inhibitory concentration (MIC) of AAEO was determined by the microdilution broth method. Time-kill curves were constructed using plate colony counting to characterize the bactericidal kinetics. The damaging effect of AAEO on the bacterial cell membrane was evaluated by scanning electron microscopy (SEM), protein and nucleic acid leakage assays, and membrane depolarization assay. The effect of AAEO on mature biofilm formation was assessed by crystal violet staining. Untargeted metabolomics was employed to analyze metabolic profile changes in the resistant strain CREO-76 and the reference strain ATCC 25922 following AAEO treatment. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) activity were measured to evaluate the effect of AAEO on bacterial redox balance. An infected full-thickness skin defect model in mice was established to assess the in vivo antibacterial activity and wound healing-promoting effect of AAEO. The MIC of AAEO against both CREO-76 and ATCC 25922 was 4 mg/mL. Time-kill curve analysis revealed that the inhibitory effect of AAEO against both the resistant strain CREO-76 and the reference strain increased in a concentration-dependent manner. AAEO treatment induced bacterial membrane depolarization, disrupted membrane integrity, and caused leakage of nucleic acids and proteins, while significantly reducing biofilm formation. Metabolomic analysis showed that AAEO exerted its antibacterial effect by perturbing the lipid composition of the bacterial cell membrane and interfering with metabolic pathways including arginine metabolism, purine metabolism, and glutathione metabolism. AAEO inhibited intracellular glutathione peroxidase (GSH-Px) activity in a concentration-dependent manner, leading to the accumulation of ROS and MDA. In vivo experiments demonstrated that AAEO exhibited good biosafety, and its potent wound healing-promoting effect was associated with the clearance of bacterial colonization in wounds and the promotion of collagen deposition in a dose-dependent manner. AAEO exhibits concentration-dependent antibacterial activity against carbapenem-resistant E. coli CREO-76. Its mechanism of action involves: inducing membrane depolarization, disrupting membrane integrity leading to protein and nucleic acid leakage, and eradicating mature biofilms; interfering with arginine, glutathione, and purine metabolic pathways; and inhibiting intracellular GSH-Px activity, inducing ROS and MDA accumulation, resulting in oxidative damage and bacterial death. In vivo experiments confirmed that AAEO possesses good biosafety and accelerates wound healing through antibacterial activity and promotion of collagen deposition. • Quantitative removal rate of biofilm shows AAEO destroys mature biofilm. • SEM indicates that AAEO disrupts the integrity of the cell membrane. • Untargeted UPLC-MS/MS metabolomics identify the antibacterial mechanism. • AAEO can disrupt normal metabolic processes in bacteria and produce oxidative stress. • AAEO can Inhibits wound bacterial growth and promotes wound healing.
Zhang et al. (Sun,) studied this question.