Phage-essential oil synergy as an evolutionary and biophysical strategy against antimicrobial resistance

The persistent challenge of global antimicrobial resistance means we can no longer rely solely on traditional small-molecule monotherapy. While bacteriophage therapy offers surgical precision, its clinical reach is often limited by biofilm-mediated protection, as well as the rapid evolution of resistance, and stability issues. At the same time, essential oils (EOs) show promising antibacterial activity, yet their clinical use remains stalled due to toxicity and volatility concerns. In this review, we summarize key biomedical concepts underpinning phage therapy and EOs and propose a shift in perspective: reframing EOs as biophysical adjuvants designed to reshape phage-bacteria interactions rather than treating them as standalone antimicrobials. We explore how EO-driven membrane disruption can prime bacteria for phage predation, enhancing phage adsorption and potentially steering populations toward more susceptible phenotypes. Moving beyond simple mixtures, we evaluate the mechanistic evidence for phage-EO synergy. We highlight the early stage of this field: current evidence is limited to in vitro studies, with a lack of preclinical and clinical validation, and significant barriers to clinical translation. However, by treating phage-EO combinations as rationally engineered systems, our review aims to map out a strategic path toward their responsible and meaningful development in the fight against resistant infections.