In light of the current global antibiotic resistance crisis, the use of bacteriophages (phages) for the treatment of bacterial infections (phage therapy) is becoming increasingly attractive. However, the interaction between phages and their bacterial targets is a complex dynamic process. Phage infectivity in vitro does often correlate poorly with in vivo bactericidal activity. Therefore a better understanding of in vivo phage-bacteria interactions and how these correlate with in vitro data is necessary to make significant progress towards the development of effective phage-based therapeutic applications.
We have characterized a set of diverse phages against Escherichia coli that can cause severe extra-intestinal infections (ExPEC) in humans and animals including sepsis. We have tested the efficacy of a four-phage combination in murine models of gut colonization and of severe infection (bacteraemia). Bacterial clearance rates and phage kinetics in our murine sepsis model differed from those determined in vitro. The colonization experiment allowed us to test the effect of prolonged in vivo co-incubation of target E. coli ST131 with the same phages in the gut. A steady-state rapidly evolved between the two microbial populations with co-existence over time (6 weeks) correlated with diverse bacterial responses.
Our work shows that the in vivo response of bacterial populations to attacking phages is complex and needs to be fully explored in order to be able to exploit the full therapeutic potential of these microorganisms.