Bacterial outer membrane lipopolysaccharide and associated Gram-negative outer membrane components (LPS/OM components)

The bacterial outer membrane (OM) of Gram-negative bacteria is a unique asymmetric lipid bilayer that serves as a critical permeability barrier, protecting the cell from environmental stressors and many antibiotics (Wikipedia, 2024). Its outer leaflet is primarily composed of lipopolysaccharide (LPS), also known as endotoxin, which consists of lipid A, a core oligosaccharide, and an O-antigen (NIH, 2020). LPS is essential for bacterial viability and is a potent stimulator of the host's innate immune system via the TLR4/MD-2 receptor complex, often leading to sepsis and inflammatory responses during infection (PubMed, 2023). Associated components, such as the Bam (β-barrel assembly) and Lpt (LPS transport) complexes, are vital for the biogenesis and maintenance of this membrane (Frontiers in Microbiology, 2023). Therapeutic strategies targeting these components include polymyxins, which disrupt the membrane by binding to lipid A, and novel inhibitors like murepavadin and darobactin that target transport and assembly proteins (Nature, 2019; NIH, 2023). Despite their efficacy, drugs targeting the OM often face challenges such as nephrotoxicity and the emergence of resistance through modifications of the LPS structure (StatPearls, 2024).

Other names

LipopolysaccharideEndotoxinGram-negative outer membraneLPSLipid AOuter membrane componentsBacterial cell envelope

Disruption of membrane integrity via Lipid A binding (Polymyxins); Inhibition of LPS transport via LptD (Murepavadin); Inhibition of OMP assembly via BamA (Darobactin); Inhibition of lipoprotein transport via LolCDE (Lolamicin); Neutralization of LPS-induced TLR4 activation (Eritoran).