Most phage therapy experiments begin and end in vitro—on a culture of target bacteria. These conditions bear little resemblance to the real-life conditions in humans and animals. Therefore, scientists created* a model that mimics the human microenvironment, where bacterial colonization actually occurs. Experiments using this model demonstrated that, under human conditions, E. coli colonies do not develop resistance to bacteriophages, as often occurs in vitro, and the phages successfully destroy most target microorganisms.

Due to the rapid spread of bacterial strains resistant to modern antimicrobials, scientists and clinicians are increasingly focusing on bacteriophages—bacterial viruses that offer an effective and safe alternative to antibiotics. Numerous cases of successful treatment of antibiotic-resistant infections with bacteriophages have been described. However, due to a number of limitations in testing and application, phages are not widely used in most Western countries. One problem is the difficulty in reproducing phage behavior in the laboratory. Experiments typically begin by studying the effects of phages on bacterial cultures in Petri dishes. Here, bacteria interact with each other and rapidly evolve, developing resistance to the tested phages. However, Petri dishes do not reproduce the conditions bacteria experience in various organs, which have their own "microenvironment"—blood vessels, surface texture, etc.

Scientists from the University of Exeter have developed* a method for replicating this microenvironment, where a single bacterium can colonize a specific area. Here, it doesn't mix with many other bacteria, and it encounters a bacteriophage specific to it. Using this new method, the scientists discovered that in this microenvironment, Escherichia coli , a bacterium that often causes food poisoning, doesn't develop genetic resistance to phages, and the phages are able to destroy most of the colony.

Study leader Dr. Stefano Pagliara noted that antibiotic resistance could prove a deadlier killer than COVID-19 if we don't find new ways to combat bacterial infections. Phage therapy, he believes, has great potential, and if it one day becomes part of routine clinical practice, it could save thousands of lives.

A paper published in PLoS Biology lays the foundation for understanding how the environment influences phage-bacteria interactions, which is essential for developing effective phage therapy drugs.

The study also showed that some bacteria survive in the microenvironment without developing genetic resistance to phages. These bacteria survive thanks to a smaller number of phage receptors on their surface. The authors of the study suggest that increasing the number of phage receptors on the bacterial surface can improve the effectiveness of phage therapy. Therefore, ways to increase the number of receptors should be sought.

* Attrill EL, Claydon R, Łapińska U, Recker M et al. Individual bacteria in structured environments rely on phenotypic resistance to phage. PLOS Biology, 2021; 19 (10): e3001406. DOI: 10.1371/journal.pbio.3001406