Lipopolysaccharide of Escherichia coli O157:H7 (O157 LPS)

Lipopolysaccharide (LPS) of Escherichia coli O157:H7 is a major structural component of the outer membrane of this enterohemorrhagic E. coli (EHEC) serotype. It is a complex glycolipid consisting of three regions: the toxic Lipid A, which anchors the molecule in the membrane; a core oligosaccharide; and the O-antigen (O157), a repeating polysaccharide chain that defines the strain's serological identity. LPS is essential for the bacterium's survival, providing a robust permeability barrier against host defenses, bile salts, and many antibiotics. As a potent endotoxin, it is recognized by the host's Toll-like receptor 4 (TLR4), triggering a massive pro-inflammatory cytokine cascade that contributes to the pathogenesis of hemorrhagic colitis and life-threatening hemolytic uremic syndrome (HUS). While LPS is a primary target for polymyxin antibiotics, which bind to Lipid A to disrupt the membrane, the use of bactericidal agents in O157:H7 infections is clinically sensitive due to the risk of triggering a surge in both endotoxin and Shiga toxin release. Current research focuses on developing novel inhibitors of LPS biosynthesis and transport, as well as neutralizing antibodies, to mitigate the severe systemic effects of infection.

Other names

O157 antigenEndotoxinE. coli O157:H7 O-antigenLipid A (Escherichia coli O157:H7)Enterohemorrhagic Escherichia coli lipopolysaccharide

Drugs targeting this molecule primarily act by binding to the Lipid A moiety to disrupt the structural integrity of the bacterial outer membrane, leading to cell lysis (e.g., polymyxins). Other therapeutic strategies involve the inhibition of enzymes in the Lipid A biosynthetic pathway, such as LpxC, or the inhibition of the Lpt transport system that moves LPS from the inner to the outer membrane. Additionally, monoclonal antibodies may be used to neutralize the endotoxin's pro-inflammatory activity or facilitate pathogen clearance.