Temperate phage-antibiotic synergy eradicates bacteria through depletion of lysogens

There is renewed interest in bacterial viruses (phages) as alternatives to antibiotics. All phage treatments to date have used virulent phages rather than temperate ones, as these can integrate into the genome of the bacterial host and lie dormant. However, temperate phages are abundant and easier to isolate. To make use of these entities, we leverage stressors known to awaken these dormant, integrated phages. Co-administration of the temperate phage HK97 with sub-inhibitory concentrations of the antibiotic ciprofloxacin results in bacterial eradication (≥8 log reduction) in vitro. This synergy is mechanistically distinct from phage-antibiotic-synergy described for virulent phages. Instead, the antibiotic specifically selects against bacteria in which the phage has integrated. As the interaction between temperate phages and stressors such as ciprofloxacin are known to be widespread, this approach may be broadly applicable and enable the use of temperate phages to combat bacterial infections.