The Invisible 'Fingerprint' That Changes How Phages Fight Bacteria

Phage therapy offers a compelling alternative to antibiotics, utilising viruses to neutralise harmful bacteria. However, ensuring these viral weapons work effectively requires precise manufacturing. Ideally, therapeutic phages are produced in defined bacterial strains free of virulence factors. Yet, a new study reveals that the specific bacterial strain used to grow these phages can drastically alter their behaviour in unexpected ways.

Researchers characterised a lytic phage known as EBHT, designed to target Staphylococcus aureus. They produced this phage in two different bacterial hosts: its original isolation host and an alternative strain named 19A2. Remarkably, while the phage’s genome, structure, and protein makeup remained identical between the two batches, their specificity shifted significantly. The alternative host 19A2 acted as a more efficient factory, producing a higher 'burst size' or yield of viruses. However, these plentiful phages suffered from a much narrower host range compared to those grown in the original strain.

The team identified the cause as the bacterial restriction-modification (R-M) systems. These internal mechanisms chemically modify DNA, adding specific methylation patterns. Because the two host strains possessed different R-M systems, they imprinted different chemical signatures onto the phage’s DNA. This illustrates a critical trade-off: the most efficient production host is not necessarily the optimal one. For therapeutic success, scientists must consider these invisible methylation patterns to ensure phages remain potent against clinical strains.