Bacteriophages versus priority pathogens: resistance mechanisms, therapeutic challenges, and opportunities for novel combinations.

Phage resistance in bacteria is a key limiting factor for phage therapy, driven by evolutionary adaptations to phage exposure, constraining targeted antimicrobial alternatives.

• Why it matters: Antimicrobial resistance is a critical global health threat, and phage therapy’s promise depends on overcoming resistance barriers that limit therapeutic effectiveness.
• What they did: The work reviews how combining phages with antibiotics, adjuvants, antimicrobial peptides, or RNA-based therapeutics could address resistance, emphasizing clinically relevant models and multi-omics plus AI to predict patterns.
• The result: It suggests that bacterial physiology and environmental context can strongly influence outcomes, and that precision combination strategies may be enabled by multi-omics and AI-driven prediction.