Lipopolysaccharide and bacterial inner membrane (LPS/IM)

Lipopolysaccharide (LPS), also known as endotoxin, is a major glycolipid component of the outer membrane of Gram-negative bacteria, with its synthesis and transport originating at the inner (cytoplasmic) membrane [PMID: 24509511]. It is composed of Lipid A, a core oligosaccharide, and an O-antigen, and is vital for maintaining the structural integrity and permeability barrier of the bacterial cell envelope [PMID: 19478799]. LPS is a potent inducer of the host immune response, acting as a ligand for the TLR4/MD-2 receptor complex, which can lead to the production of pro-inflammatory cytokines and, in severe cases, septic shock [PMID: 11544352]. Therapeutically, LPS and the bacterial membranes are targeted by polymyxin antibiotics (e.g., Colistin), which bind to the negatively charged Lipid A and disrupt membrane stability [PMID: 25130356]. Emerging therapies also target the Lpt protein machinery responsible for transporting LPS from the inner membrane to the cell surface, as well as the Lpx enzymes involved in its biosynthesis [PMID: 28387301].

Other names

EndotoxinLPSBacterial cell envelopeLipid AGram-negative bacterial cell wall

Polymyxins bind to the Lipid A portion of LPS through electrostatic interactions, displacing divalent cations (calcium and magnesium) that stabilize the membrane, leading to increased permeability and cell death. Other agents inhibit the transport of LPS from the inner membrane to the outer membrane or block its biosynthesis.