Lipopolysaccharide and anionic lipids (LPS)

Lipopolysaccharide (LPS) and anionic lipids are essential structural components of the Gram-negative bacterial cell envelope [Raetz & Whitfield, 2002]. LPS, also known as endotoxin, constitutes the majority of the outer leaflet of the outer membrane and is critical for maintaining the structural integrity and permeability barrier of the bacterium [Silhavy et al., 2010]. Anionic lipids, such as phosphatidylglycerol and cardiolipin, are found in both the inner and outer membranes and contribute to the overall negative charge of the bacterial surface [Epand et al., 2016]. These molecules serve as primary targets for several classes of antibiotics, most notably the polymyxins, which bind to the Lipid A component of LPS and displace stabilizing divalent cations like Mg2+ and Ca2+ [Velkov et al., 2013]. This interaction leads to the disruption of the membrane, leakage of cellular contents, and ultimately bacterial cell death. Beyond their structural role, LPS is a potent inducer of the host immune response via the Toll-like receptor 4 (TLR4) pathway, making it a central player in the pathogenesis of sepsis and septic shock [Alexander & Rietschel, 2001].

Other names

EndotoxinLipid ABacterial cell envelope lipidsGram-negative bacterial membraneAnionic phospholipids

Drugs like polymyxins bind to the negatively charged Lipid A of LPS and anionic phospholipids via electrostatic interactions, displacing divalent cations (Mg2+, Ca2+) that stabilize the membrane [Velkov et al., 2013]. This causes a detergent-like effect, increasing membrane permeability and leading to the leakage of cytoplasmic contents and cell death [Trimble et al., 2016].