Lipopolysaccharide (LPS) (LPS)

Lipopolysaccharide (LPS), commonly referred to as endotoxin, is a complex glycolipid that constitutes the primary structural component of the outer leaflet of the Gram-negative bacterial outer membrane (Raetz & Whitfield, 2002, Annu Rev Biochem). It is composed of three distinct regions: the hydrophobic Lipid A, a core oligosaccharide, and a distal O-antigen polysaccharide (Alexander & Rietschel, 2001, Med Microbiol Immunol). Lipid A is the conserved, bioactive moiety responsible for the potent immunostimulatory activity of LPS, acting as a ligand for the Toll-like receptor 4 (TLR4)/MD-2 complex in mammals (Park & Lee, 2013, Exp Mol Med). While essential for bacterial survival and protection against environmental stressors, the release of LPS into the bloodstream during infection can trigger an overwhelming inflammatory cascade. This systemic response can lead to severe conditions such as sepsis and septic shock (Opal, 2010, Chest). Pharmacological targeting of LPS involves membrane-disrupting antibiotics like polymyxins, which bind directly to the Lipid A portion (Zhanel et al., 2019, Drugs). Other therapeutic strategies include novel inhibitors that block LPS biosynthesis or its transport to the cell surface via the Lpt pathway. Additionally, neutralizing agents and TLR4 antagonists are explored to mitigate the host's inflammatory response to circulating endotoxin. This molecule remains a central focus for developing treatments against multi-drug resistant Gram-negative pathogens.

Other names

EndotoxinLipid AO-antigenCore oligosaccharideBacterial endotoxinPyrogen

Mechanisms include direct binding to the Lipid A moiety to disrupt the bacterial outer membrane (e.g., polymyxins), inhibition of LPS transport proteins such as LptD (e.g., murepavadin), and neutralization of circulating endotoxin to prevent activation of the TLR4/MD-2 receptor complex (e.g., eritoran, alkaline phosphatase).