In silico and in vitro assessment of antimicrobial activity of Arctium lappa L. leaf and flower essential oil against WHO priority pathogens.

Antimicrobial resistance (AMR) poses an escalating global threat, demanding the discovery of innovative therapeutics with novel mechanisms of action. Essential oils (EOs) from medicinal plants are promising candidates due to their multitarget effects and reduced risk of resistance development. This study investigates the chemical profile and antimicrobial mechanisms of essential oil obtained from the aerial parts (leaves and flowers) of Arctium lappa (ALEO), a species with strong ethnopharmacological relevance yet poorly characterized in Tunisia. Gas chromatography–mass spectrometry (GC–MS) revealed 1,3-cyclooctadiene (48.6%), caryophyllene oxide (31.7%), and aromadendrene (12.0%) as major constituents. ALEO demonstrated potent in vitro antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA ATCC 43300), Pseudomonas aeruginosa ATCC 27,853, and Candida auris clinical isolates, with MIC values comparable to reference drugs. Complementary molecular docking identified strong binding affinities of caryophyllene oxide and aromadendrene to bacterial DNA gyrase B and fungal lanosterol 14α-demethylase, while molecular dynamics simulations confirmed stable ligand–protein interactions (RMSD < 2.5 Å) and favorable binding energies (ΔG ≤ − 17 kcal/mol). Together, these findings highlight ALEO as a multitarget antimicrobial agent with therapeutic potential against WHO-priority pathogens, bridging traditional medicinal knowledge and modern drug discovery approaches.