Recombinant Human IgG1 Enhances Complement-Mediated Bacteriolysis and Macrophage Phagocytosis of Pseudomonas aeruginosa via Targeting Cell Surface Polysaccharides

Abstract

International audienceThe development of innovative therapeutics against WHO priority pathogens is an urgent global need. Here, we demonstrate the functionalities of a human antibody, previously isolated by whole cell biopanning of the phage display scFv library. The yPgi3G4 IgG1 could mediate antibody-dependent phagocytosis of Pseudomonas aeruginosa by human matured THP-1 monocytes, of which colocalization with caveolin was clearly observed at 24 h. Next, the antibacterial activity against live P. aeruginosa was demonstrated by an agglutination assay and complement-mediated killing of the bacteria. Lipopolysaccharide (LPS) extraction and Western blot (WB) analysis suggested that LPS was the target of the yPgi3G4 IgG1 antibody. A cross-reactivity assay to available isolates in Thailand and France showed that the antibody could detect 6 P. aeruginosa serotypes including several multidrug-resistant clinical isolates. This study proved the potential of using this strategy to identify a biotherapeutic for a certain quotient of multidrug-resistant P. aeruginosa and other bacterial infections