Enhanced efficiency of virulent and temperate phage combination mediated through bacterial membrane vesicles.

Since multidrug-resistant IMPORTANCE: Since the resurgence of phage therapy as a strategy to combat antibiotic-resistant bacterial infections, the use of combined virulent phages has shown promising therapeutic potential. However, naturally occurring phages are predominantly temperate, restricting their use as therapeutic agents due to concerns regarding their ability in lysogenic conversion. Here, we demonstrate that temperate phages can confer a therapeutic potential by inducing lysogenized bacteria to produce small membrane vesicles (MVs) that synergize with virulent phages in combination to suppress bacterial growth. Since MVs originate from the bacterial outer membrane, they not only retain phage receptors but also carry phage-derived biomolecules influenced by resident prophage. Potentially, they can mediate receptor transfer to phage-resistant strains via cell-MV fusion and improve phage infectivity through the combined action of phages and prophage-derived enzymes. Our findings provide insights into the role of lysogen-derived MVs and offer strategy into a novel strategy for harnessing temperate phages in therapeutic applications.