Targeting of Mammalian Glycans Enhances Phage Predation in the Gastrointestinal Tract

The human mucosal surface is a complex ecosystem comprised of a eukaryotic epithelium, a prokaryotic microbiota, and a carbohydrate-rich interface that separates them. A less characterized, third entity, that of bacteriophage (phage), parasitizes prokaryotes but generally do not interact with eukaryotic cells. In the gastrointestinal tract, the interaction of these two domains of life influences the health status of the host, especially if there is colonization with invasive pathobionts. If the pathobiont causes a symptomatic infection, treatment with antibiotics is necessary. However, antibiotics act broadly thereby killing many protective commensals and they lack the physio-chemical properties to be optimally active in the mucosa, and may have associated adverse effects, including toxicities. Here, we report a novel C3 type phage of the genus Kuravirus whose lytic cycle is enhanced in intestinal environments. The enhanced activity is encoded in the viral tail fiber gene, whose protein product binds human heparan sulfated proteoglycans and localizes the phage to the epithelial cell surface, thereby positioning it near the location of its bacterial host. This finding offers the prospect of developing epithelial-targeting phage to selectively remove invasive pathobiont species from mucosal surfaces.