This study used an integrated approach that combines microbial metabolomics, network analysis, and molecular docking to clarify how sub-inhibitory concentrations of essential oil from Mentha haplocalyx Briq.(MEO) influence the growth of Staphylococcus aureus.A total of 73 constituents were identified in the MEO using GC-MS.The MEO exhibited strong in vitro inhibitory activity against S.aureus, with a minimum inhibitory concentration (MIC) of 0.4% (volume fraction), and the antibacterial rate of MEO at this concentration against S.aureus still reached 94% within 10 h.Scanning electron microscopy showed that MEO at concentrations of 0.5×MIC and 1.0×MIC caused notable morphological changes in S.aureus, such as shrinkage, depression, and rupture.Metabolite profiling using mass spectrometry revealed significant changes in L-glutamic acid, malic acid, myo-inositol, fumaric acid, and ethanolamine in S.aureus cells during logarithmic phase, exposed to sub-inhibitory concentration (0.1×MIC) of MEO.These changes primarily indicated disruptions in inositol phosphate metabolism, energy metabolism such as tricarboxylic acid cycle and pyruvate metabolism, amino acids metabolism, and oxidative stress damage.Integration of network analysis and molecular docking suggested that menthol, menthone, α-cadinol, damascenone, carvone, and β-bourbonene may disrupt the normal growth of S.aureus by modulating key targets such as BCHE, FNTA, CES1, CES2, and FAAH.These findings provide foundational data for the comprehensive development and application of MEO in the pharmaceutical and food industries.
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