Open AccessAntibody Binding to the O-Specific Antigen of Pseudomonas aeruginosa O6 Inhibits Cell Growth
Author(s) -
Gabrielle Richard,
Colin R. MacKenzie,
Kevin A. Henry,
Evgeny Vinogradov,
J. Christopher Hall,
Greg Hussack
Publication year - 2020
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.02168-19
Subject(s) - pseudomonas aeruginosa , antigen , microbiology and biotechnology , pathogen , monoclonal antibody , antibody , serotype , biology , antibiotics , virology , bacterial outer membrane , bacteria , immunology , escherichia coli , biochemistry , genetics , gene
Pseudomonas aeruginosa is an opportunistic pathogen that is inherently resistant to many antibiotics and represents an increasing threat due to the emergence of drug-resistant strains. There is a pressing need to develop innovative antimicrobials against this pathogen. In this study, we identified the O-specific antigen (OSA) of P. aeruginosa serotype O6 as a novel target for therapeutic intervention. Binding of monoclonal antibodies and antigen-binding fragments therefrom to O6 OSA leads to rapid outer membrane destabilization and inhibition of cell growth. The antimicrobial effect correlated directly with antibody affinity. Antibody binding to the O antigen of a second lipopolysaccharide (LPS) type present in P. aeruginosa or to the LPS core did not affect cell viability. Atomic force microscopy showed that antibody binding to OSA resulted in early flagellum loss, formation of membrane blebs, and eventually complete outer membrane loss. We hypothesize that antibody binding to OSA disrupts a key interaction in the P. aeruginosa outer membrane.