Antibacterial and Antibiofilm Efficacy of 2-Phenyl Ethyl Methyl Ether Against Multidrug-Resistant Klebsiella pneumoniae.

The rise of Klebsiella pneumoniae (Kp) as an MDR pathogen has become a pressing global health challenge, contributing to UTIs and Pneumonia. A major factor underlying its persistence and antibiotic resistance is its inherent ability to form protective biofilm matrices. This study explores a natural approach to combat Kp biofilms by leveraging the antibacterial potential of plant-derived essential oils. Among bioactive compounds, 2-Phenyl ethyl methyl ether, a constituent of kewda oil, appears as a viable option. Our investigation revealed that 2-PEME exhibits significant antibacterial activity against Kp with a MIC of 50 mM, and the clinical isolate was further confirmed by morphological and molecular characterization. Notably, at a sub-MIC concentration of 25 mM, 2-PEME disrupted biofilm formation, reducing biofilm biomass by 61.17% ± 3.75% and 59.30% ± 6.24% in Kp and MTCC-109, respectively. These findings were further corroborated through microscopic analysis, providing strong evidence of 2-PEME's biofilm-inhibiting potential. To elucidate the mechanism of action, molecular docking studies were performed, which predicted strong binding affinities between 2-PEME and key biofilm-associated and drug-resistant proteins in Kp. Cell viability assays conducted on HEK-293, 3T3L1, and L929 cell lines demonstrated no cytotoxic effects, confirming their viability as a safe alternative. Computational pharmacokinetic analysis further supported its drug-like properties.