Identifying potential synergy between pleurotin and bacteriophages towards tackling multi- resistant infections.

Multidrug-resistant organisms pose a major healthcare challenge. The current limitations on antibiotic discovery, have necessitated the search for novel discovery methods and sources as well as non-antibiotic alternatives. The basidiomycete-derived, secondary metabolite pleurotin and its congeners could be a proponent of the former, as these have been shown to be effective against gram-positive bacteria, while bacteriophages (phages) could be the ultimate non-antibiotic alternative. Phages can target with great specificity (resistant) bacterial pathogens. A very promising application of bacteriophage therapy is phage-antibiotic combination (PAC) therapy, where cocktails of phage and conventional antibiotic are employed against problematic bacterial strains. In this project, we wish to examine the landscape of phage and antibiotic combination therapy research, to find out if phage-antibiotic synergy (PAS) can be achieved, which could inhibit bacterial growth, increase biofilm clearance and counteract the emergence of bacterial resistance. Along this effort, the basidiomycete-derived pleurotin and its congeners will be explored as ways to discover novel secondary metabolites of interest. An examination of the combination of pleurotin and bacteriophages targeting the gram-positive Staphylococcus aureus infections will be analysed to reveal efficiency and cytotoxicity in human cells.