IV Jornadas Latinoamericanas de Bacteriófagos

Background
Phage therapy is gaining attention as an alternative or complement to antibiotics, but its clinical adoption remains limited by practical and biological challenges: isolating phages that efficiently infect a patient’s strain is labor‑intensive, many isolates display low efficiency of plating (EOP), large‑scale production of pure, characterised stocks is costly, and bacteria rapidly evolve resistance in response to phage predation that can render a phage ineffective. Phage training exploits the natural evolutionary capacity of phages by exposing them to target bacteria under controlled conditions.

Hypothesis
Phage training can address key limitations of phage therapy by harnessing rapid phage evolution to generate phages with increased infectivity, broader host range, and improved capacity to overcome and delay bacterial resistance.

Methods: Training approaches
Three principal phage training strategies are described in the literature.
Phage evolution involves iterative exposure of phages to evolutionarily naïve bacteria while suppressing host evolution, selecting for increased infectivity or host range.
Phage–bacterial co-evolution allows both phage and host to evolve, enabling phages to counter bacterial resistance and delay its emergence.
Appelman’s protocol employs serial dilution of mixed phage populations against multiple bacterial strains, pooling lytic wells to promote host range expansion and genetic diversification.

Key results
Phage training has repeatedly demonstrated improved therapeutic traits. Phage evolution increased lytic activity and EOP (Subedi et al.). Co-evolution improved infectivity, suppressed bacterial growth, and delayed resistance (Ngiam et al.). Appelman’s protocol enabled host range expansion and recombination-driven diversification (Burrowes, Molineux, and Fralick).

Concluding remarks
While promising, phage training faces limitations including long timeframes, lack of protocol standardisation, inconsistent use of populations versus single genotypes, and incomplete characterisation. Future studies should align training strategies with clinical goals and prioritise genetically and phenotypically defined phages. A flexible, patient-tailored application of phage training may be key to integrating phage therapy into clinical practice.