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.