Lipopolysaccharide core region (LPS core) (LPS core)

The lipopolysaccharide (LPS) core region glycolipid is a vital structural component of the outer membrane of Gram-negative bacteria, situated between the hydrophobic Lipid A and the distal O-antigen (PubMed: 25100113). It is composed of an inner core, typically containing 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) and heptose residues, and an outer core consisting of various hexoses (NIH: PMC3524621). This region is essential for maintaining the stability of the bacterial cell envelope and serves as a barrier against detergents and certain antibiotics (PubMed: 11544345). Because the core region is more conserved across different bacterial species than the O-antigen, it has been a primary target for the development of cross-reactive monoclonal antibodies and vaccines intended to treat sepsis and severe Gram-negative infections (PubMed: 8492413). Therapeutic strategies involving this target focus on neutralizing the pro-inflammatory effects of circulating endotoxins or increasing the permeability of the bacterial membrane to facilitate the action of other antimicrobial agents (PubMed: 10843217). Despite its potential, clinical trials for core-targeting antibodies like Nebacumab and Edobacomab have faced challenges in demonstrating consistent survival benefits in septic patients (PubMed: 1371462). Current research continues to explore the core region as a scaffold for conjugate vaccines and as a binding site for novel antimicrobial peptides.

Other names

Core oligosaccharideLPS coreR-antigenLipopolysaccharide coreInner core and outer core region

Drugs targeting the LPS core region primarily act by neutralizing the endotoxic activity of the lipopolysaccharide complex, thereby preventing the activation of TLR4-mediated inflammatory cascades, or by disrupting the structural integrity of the bacterial outer membrane to increase susceptibility to other antibiotics (PubMed: 10843217, PubMed: 25100113).