Phages connect the biological dots of antimicrobial resistance: from genesis and spread to alternative treatment modules.

Antimicrobial resistance (AMR) poses a severe global health threat, necessitating alternatives to conventional antibiotics, which are increasingly ineffective. Phages play a dual role in both propagating and potentially mitigating AMR. They facilitate AMR dissemination primarily through transduction, with emerging evidence suggesting indirect involvement in conjugation and transformation. Phage-plasmids, a dynamic entity bridging phages and plasmids, have gained increasing attention for their role in AMR evolution. Conversely, phage therapy has demonstrated promise in targeting MDR pathogens and disrupting biofilms through lytic activity and enzymatic degradation. However, challenges, such as phage resistance, host specificity and regulatory constraints, must be addressed to enable widespread clinical implementation. While regulatory frameworks for phage therapy remain underdeveloped in many regions, initiatives such as the EMA workshop in 2015 have sought to establish pathways for regulatory approval, addressing issues related to phage standardization, phage production, quality control, clinical validation and product monitoring. Leveraging the extensive experience of Eastern European countries, where phage therapy has been successfully integrated into medical practice, may accelerate its acceptance in Western healthcare systems. Integrating phages with existing antimicrobial strategies may provide a viable approach to combating AMR. Phages thus connect the biological dots of AMR by contributing to its generation and spread, but possibly also to its resolution, likely in combination with antibiotics.