Bacterial lipopolysaccharide and outer membrane phospholipids (LPS/OMP)

Bacterial lipopolysaccharide (LPS) and outer membrane phospholipids are essential structural elements of the Gram-negative bacterial cell wall, forming an asymmetric bilayer that serves as a primary defense against environmental stressors and antibiotics (Raetz & Whitfield, 2002, Annual Review of Biochemistry). LPS is composed of three regions: the hydrophobic lipid A, which anchors the molecule in the membrane and is responsible for its endotoxic activity; a core oligosaccharide; and the O-antigen polysaccharide. In the human host, LPS is recognized by the Toll-like receptor 4 (TLR4) complex, triggering a robust inflammatory response that, if uncontrolled, can lead to sepsis and multi-organ failure (Park & Lee, 2013, Experimental & Molecular Medicine). Because the outer membrane is a significant barrier to drug entry, it is a primary target for last-resort antibiotics like polymyxins, which physically disrupt the membrane to kill the bacteria. However, the release of LPS during bacterial lysis can exacerbate inflammatory conditions, presenting a significant therapeutic challenge in treating severe infections (Hotchkiss et al., 2016, Nature Reviews Disease Primers).

Other names

EndotoxinLipid AGram-negative outer membraneLPSOuter membrane phospholipids

Polymyxin antibiotics act by binding to the lipid A moiety of LPS and the phosphate groups of phospholipids through electrostatic interactions, displacing stabilizing divalent cations (Mg2+ and Ca2+). This interaction disrupts the outer membrane's integrity, leading to increased permeability, leakage of cytoplasmic components, and bacterial cell death (Poirel et al., 2017, Clinical Microbiology Reviews). Other agents like murepavadin inhibit the transport of LPS to the outer membrane by targeting the LptD protein (Werth, 2022, StatPearls).