Phage P68 virion-associated protein 17 displays activity against clinical isolates of Staphylococcus aureus.

Phage-encoded murein hydrolases are either part of the lysis cassette or found as structural components of the phage virion. Here, we show that Staphylococcus aureus bacteriophage P68 contains a virion-associated muralytic enzyme. Protein 17 has a composite structure. The N-terminal part comprises the muralytic activity, whereas the C-terminal part is required for binding to the cell surface. A high multiplicity of infection with phage P68 caused rapid lysis, and purified protein 17 triggered premature lysis when added to S. aureus cells prior to infection with P68, suggesting that it functions to weaken the murein at the site of phage DNA entry. Protein 17 displayed activity against clinical S. aureus isolates, which are resistant to infection by phage P68, demonstrating that the protein targets surface structures distinct from the phage receptor. This broad activity spectrum of protein 17 could qualify virion-associated muralytic enzymes as attractive antimicrobials.