The intrinsic resistance of Gram-negative bacteria largely stems from their highly impermeable outer membrane . This outer membrane is a highly asymmetrical bilayer, consisting of lipopolysaccharides (LPS) in the outer leaflet and a combination of phospholipids -mainly PE and PG -and varying levels of cardiolipins in the inner leaflet . Although the bilayer's hydrophobic thickness is similar to that of typical phospholipid bilayers, other physicochemical properties are significantly distinct . The dense layer of sugar residues in the LPS serves as a unique steric and electrostatic barrier against antibiotic penetration, affecting bilayer dynamics and porin functionality.