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One-two punch : phage-antibiotic synergy observed against staphylococcus aureus by combining pleurotin and phage K

Michaël Dagne Tadesse, Nala Ali, Martha White, Lijiang Song, Fabrizio Alberti, Antonia P. Sagona 

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 S. aureus was examined. Pleurotin was isolated from the basidiomycota fungus Hohenbuehelia grisea. 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 S. aureus 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.

ACS Omega. March 2025


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