Bactericidal monoclonal antibodies specific to the LPS O-antigen from multi-drug resistant Escherichia coli clone ST131-O25b:H4 elicit protection in mice.

Antimicrobial agents and chemotherapy

PubMedID: 25779571

Szijártó V, Guachalla LM, Visram ZC, Hartl K, Varga C, Mirkina I, Zmajkovic J, Badarau A, Zauner G, Pleban C, Magyarics Z, Nagy E, Nagy G. Bactericidal monoclonal antibodies specific to the LPS O-antigen from multi-drug resistant Escherichia coli clone ST131-O25b:H4 elicit protection in mice. Antimicrob Agents Chemother. 2015;.
The worldwide-spread Escherichia coli clone ST131-O25b:H4 is responsible for a significant proportion of multi-drug resistant extraintestinal infections. We generated humanized monoclonal antibodies (mAbs) that target the lipopolysaccharide O25b antigen conserved within this lineage. These mAbs bound to the surface of live bacterial cells irrespective of the capsular type expressed. In a serum bactericidal assay in vitro, mAbs induced over 95% bacterial killing in the presence of human serum as complement source. Protective efficacy at low antibody doses was observed in a murine model of bacteremia. The mode of action in vivo was investigated by using aglycosylated derivatives of the protective mAbs. The significant binding to live E. coli cells as well as the in vitro and in vivo efficacy was corroborated in assays using bacteria grown in human serum to mimic relevant clinical conditions. Given the dry pipeline of novel antibiotics against multi-drug resistant Gram-negative pathogens, passive immunization with bactericidal antibodies offers an alternative therapeutic option to control infections caused by E. coli ST131-O25b:H4.