Characterization and host range prediction of Staphylococcus aureus phages through receptor-binding protein analysis

Highlights•Receptor-binding proteins (RBPs) of 335 S aureus phages were identified•Most S. aureus phages encode two distinct RBPs•15 recombinant RBPs bound to wall teichoic acid (WTA) polymers•The new PhARIS tool predicts the host binding of new S. aureus phagesSummaryBacteriophages are crucial in bacterial communities and can be used for therapy of multidrug-resistant pathogens such as Staphylococcusaureus. However, the host range of new phages remains difficult to predict. We identified the receptor-binding proteins (RBPs) of 335 S. aureus-infecting phages, yielding 8 distinct RBP clusters. Recombinant representative RBPs of all clusters, including several subclusters, were analyzed for binding to S. aureus strains differing in potential phage receptor structures. Notably, most of the phages encoded two separate RBPs, and all RBPs used S. aureus wall teichoic acid (WTA) polymers as receptors, albeit with varying preference for WTA glycosylation patterns and backbone structures. Based on these findings, a sequence-based tool for predicting the adsorption of new phages was developed. Moreover, one of the RBPs proved useful for identifying S. aureus-type WTA in other bacterial species. These findings facilitate the characterization of phage and bacterial isolates and the development of phage therapies.Graphical abstract