Bacterial outer membrane lipopolysaccharide and phospholipid components (LPS)

The bacterial outer membrane lipopolysaccharide (LPS) and phospholipid components constitute the primary structural and protective barrier of Gram-negative bacteria (Raetz & Whitfield, 2002). LPS, also known as endotoxin, is a complex glycolipid consisting of three regions: the hydrophobic Lipid A, a core oligosaccharide, and a distal O-antigen polysaccharide (Simpson & Trent, 2019). It is essential for bacterial viability, providing resistance against hydrophobic antibiotics, detergents, and host immune factors (Simpson & Trent, 2019). In the context of human disease, LPS is a potent pro-inflammatory molecule that triggers the innate immune system via the Toll-like receptor 4 (TLR4) complex, which can lead to life-threatening sepsis and septic shock (Beutler & Rietschel, 2003). Therapeutic strategies targeting these components include polymyxin antibiotics, which physically disrupt the membrane by binding to Lipid A, and novel inhibitors that block the transport of LPS to the cell surface (Zhanel et al., 2019).

Other names

LipopolysaccharideEndotoxinGram-negative outer membraneLipid AO-antigenCore oligosaccharide

Drugs like polymyxins bind to the negatively charged phosphate groups of the Lipid A component of lipopolysaccharides, displacing divalent cations (calcium and magnesium) that stabilize the outer membrane (Zhanel et al., 2019). This displacement leads to increased membrane permeability, leakage of intracellular contents, and eventual cell death (Zhanel et al., 2019). Other agents, such as murepavadin, inhibit the LptD protein involved in the transport of LPS to the outer membrane, thereby preventing the assembly of a functional barrier (Simpson & Trent, 2019).