Escherichia coli phage ΦPNJ-9 adheres to mucus via a variant Hoc protein

Abstract

The rise in antibiotic-resistant pathogenic bacteria has sparked renewed interest in phage therapy as a promising alternative, particularly for targeting intestinal pathogens due to phage’s host specificity. However, clinical applications have revealed that many phages are ineffective in eliminating bacteria within the gut, primarily due to the complex interactions between the phage and the gut environment. However, the mechanisms underlying these interactions remain poorly understood. Our previous study demonstrated that a T4-like phage adheres to the intestinal mucosa through the interaction between its Hoc protein and MUC2 in the mucus. Whether this model is widespread among T4-like phages remains unknown. Here, we characterize a variant Hoc protein from a T4-like phage, and identify new binding sites within this protein. Our findings suggest that the interaction between Hoc and MUC2 is likely common, but the critical binding sites vary depending on the specific phage.