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The Shigella sonnei lipopolysaccharide (LPS) core is a vital structural glycolipid located in the outer membrane of the Gram-negative bacterium Shigella sonnei, which is a major global cause of bacillary dysentery (Kweon, 2008). The LPS molecule consists of the endotoxic Lipid A, a conserved core oligosaccharide, and the O-specific polysaccharide (O-antigen), the latter of which is the primary target for protective immunity (Altmann et al., 2015). In S. sonnei, the LPS is unique because the O-antigen genes are located on a large virulence plasmid (pInv), and loss of this plasmid results in a "rough" phenotype expressing only the LPS core (Formal et al., 1981). This core region is essential for bacterial survival, providing resistance to environmental stressors and host immune factors like the complement system (Morona et al., 1995). Therapeutic interventions primarily focus on the LPS as a vaccine antigen; for instance, the bioconjugate vaccine Flexyn2a targets the S. sonnei O-antigen to induce protective IgG antibodies (Cohen et al., 2014). Furthermore, the LPS structure is the target for polymyxin antibiotics, which bind to the Lipid A and core regions to disrupt membrane integrity, although the pro-inflammatory nature of the Lipid A moiety poses a risk of endotoxicity during treatment (Nation et al., 2015).
Vaccines induce the production of O-antigen-specific serum IgG and mucosal IgA antibodies that mediate bacterial opsonophagocytosis and neutralization (Cohen et al., 2014). Polymyxin antibiotics exert their effect by binding to the negatively charged phosphate groups of the Lipid A and core regions, leading to the displacement of divalent cations and subsequent disruption of the outer membrane (Nation et al., 2015).
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