Bactericidal monoclonal antibodies specific to the lipopolysaccharide O antigen from multidrug-resistant Escherichia coli clone ST131-O25b:H4 elicit protection in mice

Antimicrobial Agents and Chemotherapy
Valéria SzijártóGábor Nagy

Abstract

The Escherichia coli sequence type 131 (ST131)-O25b:H4 clone has spread worldwide and become responsible for a significant proportion of multidrug-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 >95% bacterial killing in the presence of human serum as the 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 and the in vitro and in vivo efficacy were corroborated in assays using bacteria grown in human serum to mimic relevant clinical conditions. Given the dry pipeline of novel antibiotics against multidrug-resistant Gram-negative pathogens, passive immunization with bactericidal antibodies offers a therapeutic alternative to control infections caused by E. coli ST131-O25b:H4.

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Citations

Jul 9, 2016·The Journal of Antimicrobial Chemotherapy·Nicolas DufourUNKNOWN ColoColi group
Jan 23, 2016·The Lancet Infectious Diseases·Lloyd CzaplewskiJohn H Rex
Apr 25, 2018·Antimicrobial Agents and Chemotherapy·Luis M GuachallaValéria Szijártó
Sep 7, 2017·Antimicrobial Agents and Chemotherapy·Luis M GuachallaValéria Szijártó
Feb 28, 2019·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Roberto VivasSona Jain
May 21, 2019·Therapeutic Advances in Urology·Alicia López Romo, Rodolfo Quirós
Dec 20, 2018·Frontiers in Immunology·Michele MuttiValéria Szijártó
Mar 25, 2017·Age and Ageing·Victoria EwanJohn Simpson
Mar 11, 2020·Nature Chemical Biology·Bradley R ClarkeChris Whitfield

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