Steering the course: targeting and exploiting surface receptors in phage therapy

The global rise of antibiotic resistance highlights the urgent need for alternative therapeutics such as bacteriophages (phages). Phages exert selective pressure that can "steer" bacteria toward reduced pathogenicity, increased antibiotic susceptibility, or immune clearance. A receptor-focused steering strategy is especially powerful since many phage receptors are also critical for bacterial fitness and virulence. Effective therapy requires identifying these receptors during characterization and combining phages that target distinct, conserved structures to minimize resistance. We review the current state of phage steering research and highlight guidelines emphasizing receptor identification for rational, durable therapeutic design. While this review focuses on P. aeruginosa, the findings and implications can be extended to other multi-drug resistant pathogens.