From Binding to Antibiotic Action: Phage Display as a Translational Platform for Antimicrobial Discovery, Antibiotic Rescue, and Precision Therapy

Antimicrobial resistance threatens human and animal health, while the development of new antibacterial agents remains slow. Phage display can identify peptides and antibody fragments for bacterial targeting, antimicrobial engineering, antibiotic potentiation, delivery, and diagnostics. This narrative review examines the evidence needed to connect ligand selection with antibacterial benefit. We distinguish enrichment and phage-associated binding from the activity of the intended soluble or carrier-bound product, and compare functional, microbiological, safety, resistance, and translational endpoints. We propose the Binding-to-Antibiotic Action (B2A) framework as an unvalidated, application-specific guide to evidence requirements, organized around display-related limitations such as avidity, propagation bias, and non-native target presentation. Its five domains cover binding relevance, biological function, antibacterial or antibiotic-related benefit, safety and resistance, and translation. Diagnostic candidates require a parallel pathway based on analytical performance, clinical validity, and decision impact. Representative studies demonstrate enzyme inhibition, targeted antimicrobial peptides, antibiotic delivery, and bacterial detection; however, evidence remains heterogeneous and predominantly preclinical. Sequencing, computational design, and chemical diversification can support discovery but cannot replace experimental validation. The principal opportunity is to connect molecular recognition with measurable therapeutic or diagnostic benefit across human, veterinary, food, aquatic, and environmental settings.