Bacterial outer membrane lipopolysaccharide and phospholipid (LPS) (LPS)

The bacterial outer membrane of Gram-negative bacteria is a specialized asymmetric lipid bilayer that serves as the primary defense mechanism against environmental threats. The outer leaflet is predominantly composed of lipopolysaccharide (LPS), a complex glycolipid consisting of Lipid A, a core oligosaccharide, and an O-antigen, while the inner leaflet contains phospholipids (Nikaido, 2003, Microbiology and Molecular Biology Reviews). This structure functions as a selective permeability barrier that prevents the entry of many antibiotics and detergents into the cell. LPS is also a potent endotoxin that triggers the host's innate immune response via the Toll-like receptor 4 (TLR4) pathway, which can lead to life-threatening sepsis and systemic inflammation (Raetz & Whitfield, 2002, Annual Review of Biochemistry). Therapeutic agents like polymyxins target this structure by binding to the negatively charged Lipid A, displacing stabilizing divalent cations and physically disrupting the membrane (Velkov et al., 2013, Future Microbiology). Modern drug development also focuses on inhibiting the transport proteins responsible for assembling these components, such as the Lpt pathway (Srinivas et al., 2010, Science). Disruption of this target is a critical strategy for treating multidrug-resistant infections, though it carries risks of toxicity and inflammatory flares.

Other names

EndotoxinLipoglycanGram-negative outer membraneLipid ABacterial outer membrane lipopolysaccharide and phospholipids in gram-negative bacteriaOuter membrane lipids

Binding to the Lipid A moiety of lipopolysaccharides and displacement of stabilizing divalent cations (Mg2+, Ca2+), resulting in the physical disruption of the outer membrane and increased cellular permeability (Velkov et al., 2013, Future Microbiology; Nikaido, 2003, Microbiology and Molecular Biology Reviews). Additionally, some agents inhibit the LptD protein involved in LPS transport to the outer membrane (Srinivas et al., 2010, Science).