Purpose: The purpose of this study was to evaluate the antibacterial activity and mechanism of linalool against Methicillin-resistant Staphylococcus aureus (MRSA). Methods: The determination of the antibacterial activity of linalool against clinically isolated MRSA strains was based on the minimum inhibitory concentration (MIC) and growth curve analysis. Finally, the inhibition mechanism of linalool was elucidated through metabolomic analysis and molecular docking. Results: Among the isolated strains, penicillin resistance was found to be the highest, while resistance to daptomycin/quinupristin-dalfopristin, linezolid, vancomycin, tetracycline, telithromycin, and levofloxacin was not observed. The MIC range of linalool was 211.24– 1.65 μg/mL, with MIC₅₀ and MIC₉₀ values of 13.2 μg/mL and 105.62 μg/mL, respectively. Metabolomic analysis revealed that linalool interferes with various substance metabolisms and energy metabolism in MRSA, with the glutathione pathway potentially being a key pathway affected by linalool. Molecular docking revealed that linalool exhibited good binding potential to the target glutathione. Conclusion: This study suggests that linalool could be developed as a drug or preservative to inhibit MRSA growth.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by dysregulated immunity, skin barrier dysfunction, and cutaneous microbiome dysbiosis. While current therapies face limitations, Thuja sutchuenensis essential oil (TEO) shows promise due to its multi-target potential. We sought to explore the beneficial effects of TEO and delve into its mechanistic actions in a mouse model of AD. We combined network pharmacology with in vivo validation to evaluate the therapeutic efficacy and mechanisms of TEO in an AD model, and confirmed network-predicted targets in an in vitro inflammatory cell model. In AD mice, TEO alleviated pruritus and epidermal hyperplasia, suppressed systemic IL-4/TNF-α and IgE, and partially normalized serum ALB, LDL-C, and HDL-C. Microbial diversity increased after treatment, although potentially pathogenic taxa (Arthrobacter sp. and Corynebacterium mastitidis) remained enriched. Machine-learning analysis indicated the highest predicted metabolic activity in CK controls, whereas the AD and TEO groups showed elevated pathogenic phenotype scores. Network pharmacology prioritized active compounds [(E)-ligustilide, senkyunolide A, 3-butylisobenzofuran-1(3H)-one, butylated hydroxytoluene, Z-buthlidenephthalide, and β-Myrcene] and core targets (TNF, PTPRC, CCR5, JAK1), implicating T-cell receptor signaling, Staphylococcus aureus infection, and STAT3 pathways. Docking and molecular dynamics supported strong, stable binding of major constituents to JAK1, and Western blotting confirmed TEO-mediated inhibition of the JAK1/STAT3 axis. TEO effectively alleviates atopic dermatitis symptoms by modulating immune responses and enhancing microbial diversity. It targets key signaling pathways, such as JAK1/STAT3, highlighting its potential as a therapeutic option for AD.

Methicillin-resistant Staphylococcus aureus (MRSA), as one of the main pathogens causing skin and soft tissue infections, poses challenges in treatment due to its high resistance to antibiotics. As one of the efficacious essential oil components in numerous traditional Chinese medicines, linalool was believed to possess antimicrobial activity against pathogenic microorganisms. Here, we investigated the therapeutic effects of linalool on MRSA-infected mice by examining their post-treatment outcomes. This was done through observations of physiological conditions, pathological sections, inflammatory factors, and changes in the skin microenvironment. We have confirmed the effectiveness of linalool in treating MRSA infections. Mice treated with linalool exhibited more pronounced signs of recovery, such as reduced skin necrosis, increased fibroplasia, greater neovascularization, and resolution of inflammatory infiltration. In addition, there was an improvement in the inflammatory environment, with a decrease in inflammatory factors. The microbial composition on the skin surface also confirmed this improvement. After linalool treatment, mice exhibited better species diversity on the skin, making it easier to maintain the skin's homeostasis. The excellent performance of linalool in combating MRSA infections provides a new direction for the search for new antibiotics against multidrug-resistant bacteria, highlighting the potential of linalool as a promising anti-MRSA drug.

The online version contains supplementary material available at 10.1038/s41598-026-49057-2.

Background: Staphylococcus aureus is responsible for the majority of skin and soft tissue infections, which are often diagnosed at a late stage, thereby impacting treatment efficacy. Our study was designed to reveal the physiological changes at different stages of infection by S. aureus through the combined analysis of variations in the skin microenvironment, providing insights for the diagnosis and treatment of S. aureus infections.Methods: We established a murine model of skin and soft tissue infection with S. aureus as the infectious agent to investigate the differences in the microenvironment at different stages of infection. By combining analysis of the host immune status and histological observations, we elucidate the progression of S. aureus infection in mice.Results: The results indicate that the infection process in mice can be divided into at least two stages: early infection (1–3 days post‐infection) and late infection (5–7 days post‐infection). During the early stage of infection, notable symptoms such as erythema and abundant exudate at the infection site were observed. Histological examination revealed infiltration of numerous neutrophils and bacterial clusters, accompanied by elevated levels of cytokines (IL‐6, IL‐10). There was a decrease in microbial alpha diversity within the microenvironment (Shannon, Faith's PD, Chao1, Observed species, Simpson, Pielou's E). In contrast, during the late stage of infection, a reduction or even absence of exudate was observed at the infected site, accompanied by the formation of scabs. Additionally, there was evidence of fibroblast proliferation and neovascularization. The levels of cytokines and microbial composition gradually returned to a healthy state.Conclusion: This study reveals synchrony between microbial composition and histological/immunological changes during S. aureus‐induced SSTIs.

Purpose Geraniol, an active component found in the essential oil of various medicinal plants, possesses a wide range of antibacterial properties, including against E. coli. Nevertheless, the precise inhibitory mechanism of geraniol on E. coli remains elusive. Methods Co-cultivation of multidrug-resistant Escherichia coli with geraniol was performed to investigate changes in biomass, gene expression, intracellular iron concentration, phagocytic activity, and complement-mediated killing ability. Additionally, protein expression alterations were assessed to evaluate the regulatory effects of geraniol. Results The compound geraniol demonstrated a downregulation of ydiv and iron metabolism gene fepA, fecB and fhuF expression. Concomitantly, it was observed that linalool led to a decrease in intracellular iron ion concentration. Meanwhile, treatment of E. coli with geraniol resulted in a downregulation of ompW gene expression. Additionally, it led to a decrease in the killing ability of antiserum complement and an increase in the phagocytic capacity of macrophages. Furthermore, geraniol demonstrated augmented binding effects, possibly facilitated through hydrogen bonding, relying on structural simulation or MST. Conclusion These results suggested for the first time that geraniol by regulating the iron transport-related proteins YdiV, thereby decreasing the ability of antiserum complement, and an increase in the phagocytic capacity of macrophages exerting inhibited E. coli.