Researchers at the University of California San Diego have developed “trained” bacteriophages that show expanded effectiveness against antibiotic-resistant bacteria, addressing one of the most critical challenges in modern medicine.

Bacteriophages, or phages, are viruses that specifically infect and kill bacteria but traditionally struggle to affect a broad range of resistant strains due to their high host specificity.

By using a technique called experimental evolution, scientists co-cultured phages with Klebsiella pneumoniae—a dangerous multi-drug-resistant pathogen—over 30 days, allowing the phages to naturally adapt to bacterial defenses and improve their infection capabilities.

The trained phages demonstrated enhanced killing ability against a broader spectrum of K. pneumoniae strains and sustained suppression of bacterial growth compared with untrained counterparts. Genetic analyses showed that the evolved phages acquired mutations in genes responsible for recognizing and binding to bacterial cells, which likely contributed to their improved effectiveness.

These adaptations enable phages to overcome some of the limitations that have historically hindered phage therapy, such as narrow host range and rapid bacterial resistance.

Senior author Dr. David T. Pride and his team believe this “training” approach could be expanded to target other resistant pathogens, offering a promising new avenue for phage-based treatments beyond conventional antibiotics.

As antibiotic resistance continues to rise worldwide, these findings support the potential of phage therapy as a powerful alternative or complement to traditional antimicrobial drugs, helping to fill a critical gap in the fight against drug-resistant infections.