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O-specific polysaccharide (also called O-antigen, O-polysaccharide or OPS) is the long, repetitive glycan chain of the lipopolysaccharide (LPS) on the outer membrane of Gram-negative bacteria, forming the outermost domain of LPS and being covalently attached to the core oligosaccharide and lipid A.[3][7][9] It consists of repeating oligosaccharide units (typically 2–8 or 3–5 sugars) that can extend to dozens of repeat units and shows remarkable structural diversity between and within bacterial strains, with variability in sugar composition, linkages and non-stoichiometric modifications such as O-acetylation, glycosylation, methylation or phosphorylation.[1][5][6][7] This diversity makes the O-specific polysaccharide the main determinant of O-serotype and a key antigenic structure recognized by host antibodies, forming the basis for O-serotyping of many Gram‑negative pathogens including Escherichia coli, Shigella and Klebsiella.[3][5][6][8][10] Biologically, the O-specific polysaccharide contributes to virulence and host interaction by mediating adhesion or interaction with epithelial cells, by modulating complement activation and deposition, and by helping bacteria evade phagocytosis and complement-mediated lysis; long O-chains can prevent effective assembly of the membrane attack complex at the bacterial surface and confer resistance to host defense factors such as complement and cationic antimicrobial peptides like polymyxin B.[1][4][5] In pathogens such as Shigella, the O-specific polysaccharide is both an essential virulence factor and a protective antigen: IgG antibodies directed against the O-specific polysaccharide can confer immunity and even help cure established infection through complement-dependent bacteriolysis and inhibition of epithelial invasion.[2] Because of this antigenic and virulence role, O-specific polysaccharides are used as components of conjugate vaccines and are important bacterial antigens and serotyping markers, but they are not single, well-defined therapeutic targets like individual receptors or enzymes; the label “O:2 antigen” most likely refers to a particular O-serotype (for example, a specific Klebsiella pneumoniae O2 antigen) rather than a distinct, universally defined molecular target, and thus the name “O-specific polysaccharide O:2 antigen” is imprecise and underspecified without a species or serotype context.[6][8][10]
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