Tailoring Effective Phage Cocktails for Long-Term Lysis of Escherichia coli Based on Physiological Properties of Constituent Phages

Background: Bacteriophage (phage) therapy has regained attention as an alternative to antimicrobial agents for eliminating bacteria; however, the emergence of phage-resistant bacteria during the therapy is a major concern. One method to control this emergence is to create a cocktail composed of multiple phages. Materials and Methods: In this study, we isolated 28 phages infecting Escherichia coli and evaluated their bacteriolysis (lysis) activity, lytic spectrum, adsorption rate constant, burst size, and titer of a 1-day incubation, followed by clustering of the phages based on these physiological characteristics. Results: The variation in lysis onset time and duration was more significant for cocktails of phages from different clusters than for phage cocktails from the same cluster. Conclusions: This suggests that a combination of phages with different physiological characteristics is necessary to create a cocktail that rapidly and continuously lyses bacteria over a prolonged duration while suppressing the emergence of resistant bacterial strains.