Coevolutionary phage training expands phage host range: Driven by tail fiber mutations in Pseudomonas aeruginosa lytic phage?

The rise of antibiotic-resistant bacteria, particularly multidrug-resistant Pseudomonas aeruginosa (P. aeruginosa), represents a critical challenge to global health security. Bacteriophages, with their ability to target and lyse specific bacterial pathogens, present a promising alternative through phage therapy. However, their narrow host range limits therapeutic applications. In this study, we developed an evolutionary system to expand the host range of P. aeruginosa phage pap17. Through one-host and dual-host experimental evolution, pap17 was co-cultured with permissive and non-permissive bacterial hosts. Post-evolution, pap17 gained the ability to infect previously non-permissive strains while retaining infectivity against original hosts. Genomic analysis identified key mutations in the tail fiber protein, critical for host range expansion. Evolved phages exhibited enhanced stability and lytic activity under varying environmental conditions. These findings demonstrate that evolved phages can be trained to combat a broader range of antibiotic-resistant strains, offering a potential solution to multidrug-resistant P. aeruginosa infections.