One-Two Punch: Phage-Antibiotic Synergy Observed against <i>Staphylococcus aureus</i> by Combining Pleurotin and Phage K

The surge in antibiotic-resistant <i>Staphylococcus aureus</i> infections has been deemed a major public health concern. There is an urgent need for novel antimicrobial therapies, chemical and nonantibiotic. The basidiomycota-derived, secondary metabolite pleurotin has been shown to be effective against Gram-positive bacteria, while bacteriophages could be the ultimate nonantibiotic alternative. In this study, the combination of pleurotin and phage K targeting <i>S. aureus</i> was examined. Pleurotin was isolated from the basidiomycota fungus <i>Hohenbuehelia grisea</i>. The cytotoxicity of pleurotin was assessed in two human cell lines in comparison to pleuromutilin, vancomycin, and phage K. The antibiotics were then tested independently or in combination with phage K against two <i>S. aureus</i> strains. Cytotoxicity of pleurotin in human cells was comparable to vancomycin and pleuromutilin. Results suggest that adding phage K has a synergistic effect and can lower the MIC for pleurotin, pleuromutilin, and vancomycin. This demonstrates that pleurotin could be a viable antistaphylococcal drug.