Staphylococcus aureus Cell Envelope as a Target of (‐)‐Globulol

(‐)‐Globulol is a sesquiterpenoid with a variety of biological activities such as antifungal, antiparasitic, and anticomplexinase. However, the potential antibacterial properties of (‐)‐globulol remain uncertain. Here, the antibacterial effects of (‐)‐globulol against Staphylococcus aureus ( S. aureus ) were evaluated by assays of bacterial growth profiles, cell surface hydrophobicity (CSH), and growth phenomenon of bacteria in the liquid culture medium, cellular microstructure, permeability of cell envelopes, and liquid chromatography–mass spectrometer (LC‐MS) nontargeted metabolomics. The result of the bacterial growth assay showed that the minimum inhibitory concentration (MIC) value of (‐)‐globulol against S. aureus was 7.81  μ g/mL. When exposed to (‐)‐globulol, dose‐dependent aggregation of S. aureus was observed, triggered by increased CSH, disruption of the cell envelope, and cell wall integrity. Metabolomic analysis exhibited fluctuations in metabolites associated with S. aureus cell membranes, such as upregulation of N ‐acetyl glutamic acid and biotin and downregulation of cytidine diphosphoglycerol and D ‐glucaric acid, indicating their inhibition. Simultaneously, cell wall synthesis was also disrupted by the upregulation of L ‐tryptophan and palmitoleic acid. In summary, we confirm that cell membrane disruption by (‐)‐globulol plays a key role in its antimicrobial activity.