The Current Landscape of Phage–Antibiotic Synergistic (PAS) Interactions

Abstract

Background: In response to the urgent need for new antibiotics targeting high-priority MDR pathogens, bacteriophages (phages) have emerged as promising non-traditional antimicrobial agents. Phages are viruses that infect bacteria and induce cell lysis through mechanisms distinct from those of antibiotics, making them largely unaffected by most antibiotic resistance mechanisms. Importantly, phages have been shown to work cooperatively with an array of clinically useful antibiotics, and phage–antibiotic synergy (PAS) represents a sophisticated strategy that may improve treatment outcomes. However, the interactions between phages and antibiotics are diverse, ranging from synergistic to antagonistic, and understanding the mechanisms underlying these interactions is crucial for developing effective PAS treatments. In this review, we summarize the potential evolutionary and molecular mechanisms that drive PAS and the current landscape of phage–antibiotic interactions. Conclusions: Towards the development of robust PAS strategies, we review in vitro methods for assessing PAS and considerations for choosing and employing candidate phage–antibiotic combinations.