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

The 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 <i>Pseudomonas aeruginosa</i> by human matured THP-1 monocytes, of which colocalization with caveolin was clearly observed at 24 h. Next, the antibacterial activity against live <i>P. aeruginosa</i> 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 <i>P. aeruginosa</i> 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 <i>P. aeruginosa</i> and other bacterial infections.