Bacteriophages are viruses that infect and destroy bacteria. They are currently considered one of the most promising alternatives to antibiotics, especially given the global rise in antibiotic resistance. However, even phage therapy doesn't always produce the expected results. A new study published in the journal Nature Medicine helps explain why.

The story of one patient

Scientists analyzed the case of a 22-year-old man with cystic fibrosis who suffered from a severe respiratory infection caused by the bacterium Bordetella bronchialis. Due to limited treatment options, the patient was prescribed a customized bacteriophage.

Laboratory studies showed that the phage effectively killed the bacteria. However, in real-life studies, the treatment failed, and the infection continued to progress.

The immune system suddenly became an obstacle

The researchers discovered an unexpected problem: even before treatment began, the patient's body already contained antibodies capable of recognizing and neutralizing the bacteriophage.

Where did they come from? It turned out that the bacteria contained so-called prophages in its genome—fragments of viral genetic material that can be activated inside a bacterial cell. The patient's immune system had previously encountered these prophages and developed antibodies against them.

Most interestingly, these antibodies were cross-reactive—they recognized not only the bacterial prophages but also the therapeutic bacteriophage. As a result, a significant portion of the phages were neutralized before they could attack the bacteria.

Bacteria also turned out to be more cunning

The second problem lay in the bacterial population itself. Although most bacteria were sensitive to the phage, there was a small subset of cells with reduced susceptibility to the treatment.

This phenomenon is called heteroresistance. It means that even within a single infection, bacterial subpopulations with varying sensitivity to therapy can exist. While phages destroy the bulk of the bacteria, more resistant cells are able to survive and continue the infection process.

What does this mean for the future of phage therapy?

The study's results do not call into question the promise of bacteriophages. On the contrary, they help make phage therapy more precise and effective.

The authors of the study believe that before initiating treatment, it's important to test not only the bacterial susceptibility to phages but also the presence of antibodies against potential therapeutic phages. It's also important to assess whether the bacterial population contains hidden resistant subgroups.

A step towards personalized phage therapy

Modern medicine is increasingly moving toward individualized treatment. New research shows that the success of phage therapy depends not only on the correct selection of bacteriophage but also on the patient's immune system and the genetic diversity of the bacteria.

In the future, such knowledge could help create even more personalized phage therapy regimens, increasing the chances of successfully treating complex bacterial infections even when antibiotics no longer work.