Interactions between bacterial extracellular vesicles and Bacteriophages: Dual impact on bactericidal process

The escalating crisis of antimicrobial resistance (AMR) has underscored the urgent need for alternative therapeutic strategies. Among these, bacteriophage (phage) therapy has emerged as a promising candidate due to its high specificity, favorable safety profile, and self-replicating nature. Recent studies have unveiled the dual regulatory role of bacterial extracellular vesicles (BEVs) in the context of phage infection. BEVs can inhibit phage activity by acting as decoy particles that adsorb virions, while also facilitating phage propagation through mechanisms such as receptor transfer and protective delivery. This review systematically integrates current findings on the mechanisms by which phages induce BEV production, the bidirectional effects of BEVs on phage-mediated bacterial killing, and the potential of BEVs as bioengineered nanoplatforms to enhance phage delivery. Based on recent advances, we propose that engineering BEVs may overcome key clinical limitations of phage therapy, such as narrow host range and poor in vivo bioavailability. We propose that engineered BEVs represent a promising next-generation delivery platform that could significantly enhance the precision and efficacy of phage therapy against multidrug-resistant bacterial infections.