National Academy of Sciences, Proceedings of the National Academy of Sciences, 10(118), 2021
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Significance This study explores the potential of a phage, PYO Sa , for treating Staphylococcus aureus infections in combination with antibiotics. Population dynamic and genomic analysis identified a limitation and potential liability of using PYO Sa for therapy. Due to the production of potentially pathogenic atypical small colony variants, PYO Sa alone cannot eliminate S. aureus populations. However, we demonstrate that by following the administration of PYO Sa with bactericidal antibiotics, this limitation and potential liability can be addressed. The methods used in this investigation to explore the efficacy of combinations of PYO Sa and antibiotics for treating S. aureus infections can be employed to evaluate the clinical potential and facilitate the design of treatment protocols for any bacteria and phage that can be cultured in vitro.