Gram-negative bacterial lipopolysaccharide (LPS)

Gram-negative bacterial lipopolysaccharide (LPS) is a major glycolipid component of the outer membrane in Gram-negative bacteria, consisting of a lipid A anchor, core oligosaccharide, and variable O-antigen polysaccharide. The lipid A portion embeds in the outer leaflet, providing structural asymmetry and forming a permeability barrier that excludes hydrophobic antibiotics, detergents, and bile salts, which is essential for bacterial survival in hostile environments. While LPS is critical in organisms like Escherichia coli and Salmonella, its essentiality varies by species, with some like Neisseria meningitidis viable without it. In pathogenesis, LPS acts as an endotoxin; its lipid A strongly activates host Toll-like receptor 4 (TLR4)/MD-2, triggering innate immune responses that can escalate to sepsis and cytokine storms during infection. Bacteria modify LPS structures (e.g., hypoacylation) to evade immunity, enhancing virulence in pathogens like Yersinia pestis. Therapeutically, LPS is targeted by polymyxins that permeabilize the membrane and emerging inhibitors of its biosynthesis pathway (e.g., LpxC), offering potential antibiotics against multidrug-resistant Gram-negatives, though challenges include toxicity and strain-specific vulnerabilities.

Other names

LipopolysaccharideEndotoxinLipooligosaccharide (LOS)

Disruption of outer membrane permeability; Inhibition of LPS synthesis enzymes (e.g., LpxC, LpxA) leading to accumulation of toxic precursors and cell death