Bactericidal Monoclonal Antibodies Specific to the Lipopolysaccharide O Antigen from Multidrug-Resistant Escherichia coli Clone ST131-O25b:H4 Elicit Protection in Mice | Zendy

Valéria Szijártó | Zendy; Luis Miguel Guachalla | Zendy; Zehra Visram | Zendy; Katharina Hartl | Zendy; Cecília Varga | Zendy; Irina Mirkina | Zendy; Jakub Zmajkovic | Zendy; Adriana Badarau | Zendy; Gerhild Zauner | Zendy; Clara Pleban | Zendy; Zoltán Magyarics | Zendy; Eszter Nagy | Zendy; Gábor Nagy | Zendy

Open Access

Bactericidal Monoclonal Antibodies Specific to the Lipopolysaccharide O Antigen from Multidrug-Resistant Escherichia coli Clone ST131-O25b:H4 Elicit Protection in Mice

Author(s) -

Valéria Szijártó,

Luis Miguel Guachalla,

Zehra Visram,

Katharina Hartl,

Cecília Varga,

Irina Mirkina,

Jakub Zmajkovic,

Adriana Badarau,

Gerhild Zauner,

Clara Pleban,

Zoltán Magyarics,

Eszter Nagy,

Gábor Nagy

Publication year - 2015

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.04494-14

Subject(s) - microbiology and biotechnology , monoclonal antibody , escherichia coli , biology , antibody , antigen , clone (java method) , in vivo , in vitro , lipopolysaccharide , enterobacteriaceae , virology , antibiotics , bacteremia , immunology , gene , biochemistry

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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