Characterizing Phage-Host Interactions in a Simplified Human Intestinal Barrier Model

Abstract

An intestinal epithelium model able to produce mucus was developed to provide an environment suitable for testing the therapeutic activity of gut bacteriophages. We show that Enterococcus faecalis adheres more effectively in the presence of mucus, can invade the intestinal epithelia and is able to translocate after damaging tight junctions. Furthermore, Enterococcus phage vB_EfaM_A2 (a member of Herelleviridae that possesses virion associated immunoglobin domains) was found to translocate through the epithelium in the presence and absence of its host bacteria. Phage A2 protected eukaryotic cells by reducing mortality and maintaining the structure of the cell layer structure. We suggest the mammalian cell model utilized within this study as an adaptable in vitro model that can be employed to enable a better understanding of phage–bacteria interactions and the protective impact of phage therapy relating to the intestinal epithelium.

Metagenomic Analyses of Multiple Gut Datasets Revealed the Association of Phage Signatures in Colorectal Cancer

“…While all other 5 families were found to be more abundant in the CRC group, Herelleviridae , a recently established phage family in the Caudovirales order ( Barylski et al., 2020 ), was observed to be significantly depleted in the CRC group for most datasets ( Supplementary Figure S9C ). Phages in the Herelleviridae family typically infect members of the Firmicutes phylum ( Barylski et al., 2020 ) and serve as a potential treatment to the infection of intestinal epithelium-like environment ( Núñez-Sánchez et al., 2020 ).…”

“…As a relatively new viral family ( Barylski et al., 2020 ), Herelleviridae contains phage species that may have therapeutic potential for gastrointestinal infections ( Núñez-Sánchez et al., 2020 ). Phages in the Herelleviridae family typically infect members of the Firmicutes phylum ( Barylski et al., 2020 ) and have been shown to display Ig-like domains on their virions that contribute to the integrity and heath of intestinal barrier function serving as a potential treatment targeting the intestinal epithelium ( Núñez-Sánchez et al., 2020 ). Therefore, the depletion of this family may lead to intestinal epithelial dysregulation permissive to the development of tumors.…”

Roles of Gut Bacteriophages in the Pathogenesis and Treatment of Inflammatory Bowel Disease

“…In addition to the in vivo animal models, in vitro models also play vital roles in testing the therapeutic activity of gut phages. A recent study has developed an intestinal epithelium model able to produce mucus by co-culturing Caco-2 and HT29-MTX (4:1 ratio) cells ( Nunez-Sanchez et al., 2020 ). This mammalian cell model will enable a better understanding of phage-bacteria interactions and the protective effects of phage therapy.…”

Potential of Inhaled Bacteriophage Therapy for Bacterial Lung Infection

“…Depending on administration route, phage type and phage dose, and duration of phage therapy can lead to the generation of neutralizing antibodies [94]. Together with increasing evidences showing the interactions between phage and mammalian cells [95][96][97], it would be worthwhile to explore the interaction between phage formulations with lung leukocytes and epithelial cells lining the alveolar surface and the conducting airways.…”