Lipopolysaccharide and outer membrane phospholipids of Gram-negative bacteria (LPS/OMP)

Lipopolysaccharide (LPS) and outer membrane phospholipids constitute the primary structural and functional barrier of Gram-negative bacteria, protecting the cell from environmental stressors and antibiotic penetration (Raetz & Whitfield, 2002). LPS is composed of three regions: the hydrophobic Lipid A anchor, a core oligosaccharide, and the distal O-antigen (Whitfield & Trent, 2014). As a potent endotoxin, LPS is recognized by the host immune system through Toll-like receptor 4 (TLR4), triggering inflammatory cascades that can escalate to life-threatening sepsis and septic shock (Opal, 2010). Therapeutic agents such as polymyxins exploit the anionic nature of these molecules to bind and destabilize the membrane, providing a critical line of defense against multi-drug resistant pathogens (Velkov et al., 2013). However, the clinical use of such agents is often limited by significant toxicities and the risk of massive endotoxin release during bacterial lysis (Nang et al., 2021).

Other names

EndotoxinLipid ABacterial outer membrane lipidsGram-negative cell wall lipids

Drugs typically interact electrostatically with the negatively charged phosphate groups of lipopolysaccharide and phospholipids, displacing stabilizing divalent cations like calcium and magnesium. This displacement leads to the disruption of the outer membrane's physical integrity, increased permeability, and eventual cell death (Velkov et al., 2013; Trimble et al., 2016).