Characterization and host range prediction of Staphylococcus aureus phages through receptor-binding protein analysis
Janes Krusche,
Christian Beck,
Esther Lehmann,
David Gerlach,
Ellen Daiber,
Christoph Mayer,
Jennifer Müller,
Hadil Onallah,
Silvia Würstle,
Christiane Wolz,
Andreas Peschel
Affiliations
Janes Krusche
Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, 72076 Tübingen, Germany; Cluster of Excellence EXC 2124 “Controlling Microbes to Fight Infections”, University of Tübingen, 72076 Tübingen, Germany
Christian Beck
Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, 72076 Tübingen, Germany; Cluster of Excellence EXC 2124 “Controlling Microbes to Fight Infections”, University of Tübingen, 72076 Tübingen, Germany
Esther Lehmann
Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, 72076 Tübingen, Germany; Cluster of Excellence EXC 2124 “Controlling Microbes to Fight Infections”, University of Tübingen, 72076 Tübingen, Germany
David Gerlach
Microbiology, Faculty of Biology, Ludwig-Maximilians-Universität München, 82152 Martinsried, Germany
Ellen Daiber
Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, 72076 Tübingen, Germany; Cluster of Excellence EXC 2124 “Controlling Microbes to Fight Infections”, University of Tübingen, 72076 Tübingen, Germany
Christoph Mayer
Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, 72076 Tübingen, Germany; Cluster of Excellence EXC 2124 “Controlling Microbes to Fight Infections”, University of Tübingen, 72076 Tübingen, Germany
Jennifer Müller
Institute of Medical Microbiology and Hygiene, University Hospital Tübingen, 72076 Tübingen, Germany; NGS Competence Center Tübingen (NCCT), 72076 Tübingen, Germany
Hadil Onallah
Infectious Diseases, Department of Internal Medicine II, University Hospital Frankfurt, Goethe University Frankfurt, 60596 Frankfurt, Germany
Silvia Würstle
Infectious Diseases, Department of Internal Medicine II, University Hospital Frankfurt, Goethe University Frankfurt, 60596 Frankfurt, Germany; Yale Center for Phage Biology & Therapy, Yale University, New Haven, CT 06520, USA
Christiane Wolz
Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, 72076 Tübingen, Germany; Cluster of Excellence EXC 2124 “Controlling Microbes to Fight Infections”, University of Tübingen, 72076 Tübingen, Germany
Andreas Peschel
Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, 72076 Tübingen, Germany; Cluster of Excellence EXC 2124 “Controlling Microbes to Fight Infections”, University of Tübingen, 72076 Tübingen, Germany; Corresponding author
Summary: Bacteriophages are crucial in bacterial communities and can be used for therapy of multidrug-resistant pathogens such as Staphylococcus aureus. 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.