Prophage induction therapy: Activation of the lytic phase in prophages for the elimination of pathogenic bacteria

The global burden of antimicrobial resistance has resulted in an unmet need to develop novel interventions targeting pathogenic bacteria. Although phage therapy employs lytic phages to cause host-specific killing of target bacteria, regulatory hurdles have impeded its development. It is interesting to note that more significant percentages of bacterial populations harbor dormant phages called prophages. This article proposes a novel approach termed prophage induction therapy to treat bacterial infections, with CI repressor as the therapeutic target. Disruption of CI repressor-operator interaction with a small molecule leads to the activation of the lytic phase in prophages. Post-induction, phages released from lysogenic bacteria can infect their non-lysogenic counterparts, leading to their elimination. A surrogate reporter assay is proposed to screen and identify in-ducers, followed by a demonstration of proof of principle in the pathogenic bacteria of interest. Further, elim-inating a heterogeneous population of lysogenic and non-lysogenic bacteria can be demonstrated using animal models of infectious diseases. Prophage induction therapy can be potentially applied to clinical settings to target antibiotic-resistant strains of bacteria or employed as an alternative to conventional antibiotic-based treatments.

Automated summary

This article proposes a novel approach called prophage induction therapy to treat bacterial infections by disrupting CI repressor-operator interaction to activate lytic phages. The method can be used to screen for effectors and demonstrate the potential to eliminate bacterial populations in animal models.