Virulent bacteriophages are more and more frequently proposed to target bacterial pathogens resistant to multiple antibiotics. Often these pathogens are asymptomatically carried in the gastrointestinal (GI) tract of mammals. However, despite several attempts using different animal models, the use of virulent bacteriophages to efficiently reduce carriage levels have been disappointing, achieving at best a moderate reduction. We believe the lack of knowledge on the factors that influence the replication of bacteriophages in the GI tract is impeding the development of strategies to improve overall bacteriophage efficacy.
To address this question we characterized nine bacteriophages isolated using three different strains of Escherichia coli: the enteroaggregative strain 55989, the adherent invasive strain LF82 and the uropathogenic strain AL505. Each of these E. coli strains was used to colonize the GI tract of mice during three days. Using homogenized GI samples from these mice, we assessed the ex-vivo replication of the nine bacteriophages in the small and the large bowels. We found that some bacteriophages replicate efficiently regardless of the region of the GI tract while others display a differential efficacy.
Therefore, these data support our hypothesis that the local GI environment is influencing the infectivity of bacteriophages. We will discuss how to identify bacterial or host factors, as well as how, in the future, could we design ways to improve the overall efficacy of phage therapy treatments.