Isolation and characterization of broad-range Staphylococcus epidermidis sepunaviruses

Staphylococcus epidermidis is a major contributor to biofilm-associated infections, bacteraemia, and sepsis in humans. Additionally, it is an important veterinary pathogen. The spread of multi-drug resistant S. epidermidis (MRSE) poses an even greater challenge, requiring the development of antibiotic-alternative approaches. Here, we isolated four new broad-range phages capable of infecting a large panel of 65 clinical and veterinary isolates of S. epidermidis. Phages with the broadest host range produced plaques on 37% of the hosts tested and halos on an additional 40%. These phages belonged to the Sepunavirus genus, as supported by their morphology and genome analysis. A genome-wide association study identified a significant correlation between resistance to phage lysis and the presence of the sbcCD complex and the ica operon, highlighting the protective role of biofilms against the phages isolated in this study. Furthermore, distinct phage-encoded methyltransferases identified in the phage genomes may contribute to differences in host ranges. This study advances our knowledge on the diversity and characteristics of S. epidermidis phages, which could be considered as interesting tools for phage therapeutics. RepositoriesPhage genomes are available under Genbank accession numbers PV426907-PV426910. Bacterial genome sequences determined as part of this study, and all Bakta annotations, are available via Figshare (doi:10.6084/m9.figshare.29066417 and doi:10.6084/m9.figshare.29079968 respectively).