To develop phage therapy—the use of bacteriophages to treat bacterial infections in humans and animals—it's essential to understand all aspects of the interaction between phage and target bacteria in vivo . Experiments on human cell cultures, in particular, can help us understand this.

A study conducted at the University of Leicester (United Kingdom) tested the bacteriophage phiCDHS1, which is active against the bacterium Clostridium difficile . This microorganism is a common cause of complications from antibiotic therapy, causing life-threatening gastrointestinal infections and is difficult to treat due to multiple antibiotic resistance. The phiCDHS1 phage effectively killed Clostridium difficile in liquid culture, but the scientists sought to approximate the phage's operating conditions to physiological ones. To simulate the conditions of the large intestine, where C. difficile primarily reproduces, they used a culture of HT-29 tumor cells.

When studying the interaction of C. difficile An interesting phenomenon was discovered in a culture of HT-29 cells using the bacteriophage phiCDHS1: in the presence of human cells, the phages killed bacteria more effectively than in their absence. The phages reduced the number of both free-floating and adsorbed Clostridia.

The authors hypothesized that the phenomenon is explained by phage attachment to the surface of human cells, which facilitates interaction with target bacteria. Moreover, the phages were nontoxic to human HT-29 cells. No cytotoxic effects were observed when the bacteria were lysed by the phage.

The increase in phage virulence in the presence of human cells should be taken into account when determining phage activity, selecting active strains, selecting an effective therapeutic dose of phage preparations, and planning clinical trials.

* Shan J, Ramachandran A, Thanki AM, Vukusic FBI, et al. Bacteriophages are more virulent to bacteria with human cells than they are in bacterial culture; insights from HT-29 cells // Scientific Reports, 2018, 8, Article number: 5091. doi:10.1038/s41598-018-23418-y