Bacterial outer membrane lipopolysaccharide and associated phospholipids (LPS)

Bacterial outer membrane lipopolysaccharide (LPS) and associated phospholipids constitute the primary structural and functional barrier of Gram-negative bacteria (Raetz & Whitfield, 2002, Annu Rev Biochem). LPS is a complex glycolipid composed of three regions: the hydrophobic Lipid A anchor, a core oligosaccharide, and a distal O-antigen polysaccharide (PubChem, CID 11970143). This structure is essential for bacterial viability, providing resistance against hydrophobic antibiotics, detergents, and host-derived antimicrobial peptides (Nikaido, 2003, Microbiol Mol Biol Rev). In clinical settings, LPS is recognized as a potent endotoxin that binds to the TLR4/MD-2 complex on human immune cells, potentially triggering a cytokine storm that leads to sepsis and septic shock (StatPearls, 2023, Endotoxemia). Drugs like polymyxins target this structure by binding to the negatively charged phosphate groups of Lipid A, leading to membrane permeabilization and cell death (Zhanel et al., 2019, Drugs). Emerging therapies also focus on inhibiting the transport of LPS to the outer membrane or neutralizing its toxic effects during infection (Srinivas et al., 2010, Science). The associated phospholipids in the outer leaflet further contribute to the membrane's asymmetric stability and are critical for the insertion of outer membrane proteins (PubMed, PMID 25231115).

Other names

LipopolysaccharideEndotoxinGram-negative outer membraneLipid ABacterial glycolipidOuter membrane phospholipids

Polymyxins (e.g., Polymyxin B and Colistin) act by binding to the Lipid A component of LPS and displacing divalent cations (Mg2+ and Ca2+), which destabilizes the outer membrane and leads to increased permeability and cell lysis (Zhanel et al., 2019, Drugs). Other agents like Murepavadin inhibit the LptD protein, preventing the transport of LPS to the outer membrane surface (Srinivas et al., 2010, Science). Additionally, some experimental agents target the associated phospholipids to disrupt the overall membrane leaflet stability (Nikaido, 2003, Microbiol Mol Biol Rev).