Gram-negative bacterial lipopolysaccharide lipid A and anionic phospholipids (LPS Lipid A/APL)

Gram-negative bacterial lipopolysaccharide (LPS) lipid A and anionic phospholipids are fundamental structural components of the bacterial cell envelope. Lipid A serves as the hydrophobic anchor for LPS in the outer membrane and is the primary moiety responsible for endotoxic activity, triggering severe inflammatory responses via the TLR4/MD-2 receptor complex (Park & Lee, 2013, Exp Mol Med). Anionic phospholipids, such as phosphatidylglycerol and cardiolipin, contribute to the overall negative charge and stability of both the inner and outer membranes (Epand et al., 2007, Biochim Biophys Acta). These molecules are the primary therapeutic targets for polymyxin antibiotics, which are often used as a last-resort treatment for multidrug-resistant infections. By binding to these negatively charged components, drugs like Colistin displace stabilizing divalent cations, causing membrane permeabilization and bacterial lysis (Trimble et al., 2016, Cold Spring Harb Perspect Med). Understanding these targets is critical for developing new antibiotics to combat pathogens like Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae (Poirel et al., 2017, Clin Microbiol Rev).

Other names

Lipid AEndotoxinLipopolysaccharideLPSBacterial outer membrane phospholipidsAnionic phospholipids

Cationic antimicrobial agents bind electrostatically to the negatively charged phosphate groups of lipid A and anionic phospholipids. This interaction displaces stabilizing divalent cations (Mg2+ and Ca2+), leading to a disorganized outer membrane, increased permeability, and the subsequent leakage of intracellular contents, resulting in bacterial cell death (Velkov et al., 2013, J Med Chem).