Escherichia coli lipopolysaccharide O25b antigen (O25b LPS)

The Escherichia coli lipopolysaccharide O25b antigen is a specific surface-exposed carbohydrate structure uniquely associated with the ST131-O25b:H4 clonal lineage [1, 5]. This lineage is a globally dominant, multidrug-resistant (MDR) extraintestinal pathogenic E. coli (ExPEC) responsible for a high burden of urinary tract infections, bacteremia, and sepsis [6, 20]. The O25b antigen serves as a critical structural component of the bacterial outer membrane, providing a permeability barrier against antibiotics and protecting the pathogen from host immune mechanisms such as complement-mediated killing [3, 8]. Chemically, the O25b repeating unit is distinguished from the classical O25a antigen by the presence of O-acetyl-rhamnose instead of N-acetyl-fucose [5, 13]. Therapeutic efforts have focused on this epitope as a target for active immunization via conjugate vaccines, such as JNJ-63871860 (ExPEC4V), and passive immunization using monoclonal antibodies like ASN-4 [1, 10, 18]. These agents aim to induce opsonophagocytic killing and direct bactericidal activity to clear MDR infections [2, 10]. However, the development of these therapies has faced significant hurdles, including the recent discontinuation of a Phase III trial for the ExPEC vaccine due to insufficient efficacy [15].

Other names

O25b antigenST131-associated O-antigenO25b repeating unitEscherichia coli O25b lipopolysaccharideO25b epitope

Induction of opsonophagocytic killing (OPK) and complement-mediated bactericidal activity through the binding of specific antibodies to the O25b antigen, thereby facilitating bacterial clearance and neutralizing the endotoxic effects of the lipopolysaccharide [1, 2, 10].