Bacterial outer membrane lipopolysaccharide and anionic phospholipids

The bacterial outer membrane lipopolysaccharide (LPS) and anionic phospholipids serve as the fundamental structural components and primary permeability barriers of Gram-negative bacteria (Raetz & Whitfield, 2002). LPS, often referred to as endotoxin, is composed of a hydrophobic Lipid A anchor, a core oligosaccharide, and an O-antigen polysaccharide chain (Raetz & Whitfield, 2002). Anionic phospholipids, such as phosphatidylglycerol and cardiolipin, provide additional negative charge and maintain the electrochemical gradient across the membrane (Epand & Epand, 2011). These molecules are essential for bacterial survival, protecting the cell from detergents, bile salts, and many hydrophobic antibiotics (Epand & Epand, 2011). Therapeutically, these components are targeted by cationic lipopeptides such as polymyxins, which bind to the negatively charged phosphate groups via electrostatic interactions (Poirel et al., 2017). This binding displaces stabilizing divalent cations like magnesium and calcium, leading to physical disruption of the membrane and leakage of cellular contents (Poirel et al., 2017). Beyond their structural role, LPS is a potent trigger for the human innate immune system via Toll-like receptor 4 (TLR4) (Trimpa et al., 2021). Consequently, drug-induced bacterial lysis can lead to the massive release of endotoxins, potentially causing severe inflammatory responses such as sepsis or septic shock (Trimpa et al., 2021).

Other names

EndotoxinLipid ABacterial cell envelopePhosphatidylglycerolCardiolipinGram-negative outer membrane

Electrostatic binding to negatively charged phosphate groups of Lipid A and anionic phospholipids, displacement of divalent cations (Mg2+ and Ca2+), and subsequent membrane permeabilization and disruption (Poirel et al., 2017).