Lipopolysaccharide lipid A (Lipid A) (Lipid A)

Lipopolysaccharide lipid A is the highly conserved, hydrophobic anchor of the lipopolysaccharide (LPS) molecule, embedded within the outer leaflet of the Gram-negative bacterial outer membrane (Raetz & Whitfield, 2002). It is widely recognized as the 'endotoxin' component of the bacterial cell wall, responsible for the potent inflammatory response triggered during Gram-negative infections (Park et al., 2009). Lipid A is essential for bacterial viability and serves as a critical permeability barrier, protecting the cell from toxic substances. This essentiality makes it a primary target for cationic antimicrobial peptides such as polymyxin B and colistin, which bind to the lipid A phosphate groups to disrupt membrane integrity (Velkov et al., 2013). In the host, lipid A is detected by the Toll-like receptor 4 (TLR4)/MD-2 complex, which initiates a signaling cascade leading to the production of pro-inflammatory cytokines (Opal, 2010). While this immune activation is vital for controlling infection, excessive or systemic release of lipid A can lead to life-threatening conditions such as sepsis and septic shock (Opal et al., 2013). Consequently, lipid A is a major focus for both the development of novel antibiotics and the creation of anti-sepsis therapies designed to neutralize its toxic effects.

Other names

EndotoxinLipid A moietyLPS lipid ALipid A componentLipoglycan lipid A

Polymyxin antibiotics bind to the lipid A moiety of lipopolysaccharide, displacing stabilizing divalent cations and causing disruption of the bacterial outer membrane, which leads to increased permeability and cell death (Velkov et al., 2013).