Bacterial lipopolysaccharide (LPS)

Bacterial lipopolysaccharide (LPS) is a complex, amphipathic glycolipid and the primary structural component of the outer leaflet of the outer membrane of Gram-negative bacteria[1][5][7]. Composed of lipid A, a core oligosaccharide, and the highly variable O-antigen, LPS is essential for bacterial viability, outer membrane integrity, and serves as a major barrier to antibiotics and toxins[3][5][9]. LPS is also a potent stimulator of the host immune response; its lipid A portion is recognized by the innate immune system, leading to robust inflammatory reactions and, in high concentrations, endotoxic shock[3][5]. Due to its central biological roles, LPS and its biosynthesis/transport machinery (notably enzymes such as LpxA, LpxC, LpxD, LpxH, and the multi-protein Lpt transporter complex) are increasingly targeted by novel antibiotic strategies, and several experimental and approved drugs exploit LPS as either a direct target (polymyxins, experimental enzyme inhibitors) or a vulnerability[1][4][6][8][10]. The search for antibiotics that specifically impede LPS biosynthesis or integration has intensified due to its contribution to multidrug resistance and the urgent need for effective treatments against Gram-negative pathogens[1][2][4][8].

Other names

LipopolysaccharideEndotoxinBacterial outer membrane lipopolysaccharideGram-negative outer membrane lipopolysaccharide

Disruption of LPS biosynthesis (LpxA, LpxC, LpxD, LpxH inhibitors block pathway); Inhibition of LPS transport (blockade of Lpt transporter, e.g., LptD); Direct binding/disruption of outer membrane (polymyxins bind to LPS and disrupt membrane integrity)