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The **outer membrane of Gram-negative bacterium** is an asymmetric lipid bilayer unique to Gram-negative bacteria and forms the outermost barrier of their cell envelope[1][5][6][7]. Its outer leaflet is rich in **lipopolysaccharide (LPS)**, a potent endotoxin which induces a strong host immune response[1][6][7]. The inner leaflet consists mainly of phospholipids. Embedded within the outer membrane are **outer membrane proteins** (OMPs), including porins that control nutrient and antibiotic uptake, and lipoproteins such as Braun’s lipoprotein that link the outer membrane to the underlying peptidoglycan[1][5][6]. The outer membrane serves as a **permeability barrier**, protects against environmental stress and many antibiotics, and is essential for maintaining structural integrity as well as bacterial viability[5][6][7]. LPS and surface proteins displayed in the outer membrane play important roles in virulence, antibiotic resistance, immune evasion, and interaction with host tissues[7]. Although the outer membrane itself is not a "target" in the sense of being a specific molecule or receptor, it is a critical structure targeted indirectly by several antibiotic classes, such as **polymyxins and antimicrobial peptides**, as well as by drugs seeking to increase its permeability[7]. Because it is a large, multi-molecular structure rather than a single biochemical entity, it does not correspond to the usual definition of a "therapeutic target" (such as a receptor, enzyme, or transporter) but is nonetheless a major focus for novel antibacterial strategies.
Disruption of membrane integrity (by polymyxins and AMPs)[7] Increased permeability to antibiotics (by permeabilizers or mutants with defective outer membrane)[7] Inhibition of transport through porins (by some antibiotics)[1][7]
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