Convergent anti-MRSA potency across compositionally distinct essential oils: a chemotype similarity index for strain-dependent chemistry–activity analysis

Antimicrobial resistance represents a continuing threat to clinical infection management, with methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Escherichia coli identified by the World Health Organization as priority pathogens. This study evaluated the antimicrobial activity, synergistic potential, and chemical composition of six plant-derived preparations — three ethanolic extracts (nettle, thyme, rosemary) and three essential oils (lavender, lemongrass, doTERRA Peace blend) — against MRSA, methicillin-sensitive S. aureus (MSSA), and E. coli K-12 by disc diffusion, broth microdilution, post-exposure culturability, antimicrobial interactions assessed by checkerboard assay, and GC-MS profiling. Disc diffusion produced no interpretable zones of inhibition for any plant preparation tested, however broth microdilution revealed reproducible inhibitory activity within published ranges across the panel. Three essential oils achieved a median Minimum Inhibitory Concentration (MIC) of 0.39 mg/mL against MRSA despite presenting compositionally distinct chemotypes — lavender was linalool-dominated (61% combined), lemongrass was citral-dominated (76%), and the doTERRA blend was sesquiterpene-rich. Rosemary ethanolic extract achieved the same potency (0.39 mg/mL) against MSSA. No preparation produced a bactericidal reduction (≥3 log₁₀ CFU mL⁻¹) at any timepoint, with all reductions transient and recovering by 24 hours. Checkerboard combinations of plant preparations with vancomycin and ciprofloxacin were uniformly classified, according to the Fractional Inhibitory Concentration Index (FICI), as indifference/no interaction, attributable in part to inoculum-mediated effects on vancomycin MIC. To analyse the relationship between chemical composition and antimicrobial outcomes, we introduce a Chemotype Similarity Index (CSI), a chemometric framework quantifying pairwise compositional similarity between essential oils by Pearson correlation and relating it to log₂-MIC differences across strains. CSI revealed a strain-dependent chemistry–activity relationship — convergent against MRSA, monotonic against MSSA, and absent against E. coli — indicating that compositional similarity predicts antimicrobial outcomes on a strain-specific basis. The convergence of three chemotypically divergent essential oils with the same anti-MRSA potency suggested a shared membrane-disrupting mechanism operating through distinct chemical routes. Although exploratory at this scale, the CSI framework provides a reusable analytical scaffold for linking phytochemical composition to antimicrobial activity, and identifies the MRSA convergence as a specific direction for mechanistic investigation into the development of plant-derived antimicrobial adjuncts.