Gram-negative bacterial outer membrane lipopolysaccharide and anionic phospholipids (LPS)

The outer membrane of Gram-negative bacteria is a specialized asymmetric lipid bilayer where lipopolysaccharide (LPS) and anionic phospholipids are essential for structural stability and survival. LPS, also known as endotoxin, resides in the outer leaflet and functions as a primary permeability barrier that protects the bacterium from environmental stressors and antibiotics (Nikaido, 2003). Anionic phospholipids, including phosphatidylglycerol, are found in the inner leaflet and contribute to the membrane's overall negative charge, which is crucial for the binding of various antimicrobial agents (Epand et al., 2007). These components are the primary targets for the polymyxin class of antibiotics, which interact electrostatically with the negatively charged phosphate groups of Lipid A and phospholipids (Velkov et al., 2013). This interaction displaces stabilizing divalent cations like magnesium and calcium, leading to membrane disorganization, increased permeability, and cell death (Trimble et al., 2016). While targeting these structures is effective against highly resistant pathogens like Acinetobacter baumannii, it is associated with significant clinical risks, particularly nephrotoxicity and neurotoxicity (Falagas & Kasiakou, 2006).

Other names

LipopolysaccharideLPSEndotoxinLipid ABacterial outer membrane lipids

Binding to the lipid A moiety of lipopolysaccharide and anionic phospholipids via electrostatic interactions, followed by the displacement of divalent cations (Mg2+ and Ca2+), which leads to the disruption of the bacterial outer membrane and increased permeability (Velkov et al., 2013; Trimble et al., 2016).