Bacterial outer membrane lipopolysaccharide core (LPS core) (LPS core)

The bacterial outer membrane lipopolysaccharide (LPS) core is a vital structural component of the Gram-negative cell envelope, situated between the Lipid A moiety and the O-specific polysaccharide chain (Raetz & Whitfield, 2002). It plays a critical role in maintaining the integrity of the outer membrane and acting as a selective permeability barrier against toxic compounds, including certain antibiotics and host immune factors (Whitfield & Trent, 2014). The core is generally divided into the inner core, which is highly conserved and contains unique sugars like 3-deoxy-D-manno-oct-2-ulosonic acid (KDO), and the more diverse outer core (Bertani & Ruiz, 2018). In the context of infectious disease, the LPS core is a major contributor to the pathogenesis of sepsis and septic shock, as it is recognized by the host's innate immune system via the TLR4/MD-2 complex, triggering a potent inflammatory cascade (Park & Lee, 2013). Therapeutic strategies targeting the LPS core include polymyxin antibiotics, which bind to the negatively charged phosphate groups to disrupt the membrane, and various experimental monoclonal antibodies aimed at neutralizing endotoxin activity (Velkov et al., 2013; Opal et al., 2014). Despite its potential as a broad-spectrum target, clinical success has been limited by the toxicity of existing drugs and the difficulty of effectively modulating the host's systemic response to endotoxemia (Ramachandran, 2014).

Other names

Core oligosaccharideLPS core regionLipopolysaccharide coreInner core and outer core oligosaccharide

Polymyxins bind to the lipid A and core oligosaccharide regions of LPS via electrostatic interactions between the positively charged residues of the drug and the negatively charged phosphate groups of LPS, resulting in the displacement of magnesium and calcium ions that stabilize the outer membrane (Velkov et al., 2013). This leads to increased membrane permeability, leakage of cytoplasmic contents, and cell death, while also potentially neutralizing the endotoxic activity of LPS (Opal et al., 2014).