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The *bacterial outer membrane* is a unique lipid bilayer present in Gram-negative bacteria, composed primarily of phospholipids in the inner leaflet and lipopolysaccharides in the outer leaflet, with embedded proteins such as porins and lipoproteins that link to the cell wall (peptidoglycan). The *cytoplasmic membrane* (also called the inner membrane) is a phospholipid bilayer that separates the cytoplasm from the periplasmic space and contains inner membrane proteins vital for nutrient transport, energy generation, and cellular signaling. Together, these structures serve as critical physical and functional barriers, contribute to bacterial cell shape and viability, and play essential roles in antibiotic resistance and pathogenesis. The outer membrane especially protects Gram-negative bacteria from hydrophobic antibiotics and environmental threats, while its components, such as lipopolysaccharide, can trigger strong host immune responses[1][2][3][4]. Note: This entry refers to physical membranes, not a distinct molecular therapeutic target, making it non-canonical as a drug target. Drug development typically focuses on membrane-embedded proteins or lipopolysaccharide components, not the membrane structures themselves[1][3][4].
Membrane disruption (polymyxins break the integrity of the outer membrane); Increased permeability allowing antibiotic entry (e.g., EDTA-mediated LPS removal); Inhibition of membrane protein assembly or function (certain antibiotics target specific OMPs)
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