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标题：Evaluating the potential efficacy and limitations of a phage for joint antibiotic and phage therapy of Staphylococcus aureus infections
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作者：Brandon A. Berryhill ; Douglas L. Huseby ; Ingrid C. McCall 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：10
页码：1
DOI：10.1073/pnas.2008007118
出版社：The National Academy of Sciences of the United States of America
摘要：In response to increasing frequencies of antibiotic-resistant pathogens, there has been a resurrection of interest in the use of bacteriophage to treat bacterial infections: phage therapy. Here we explore the potential of a seemingly ideal phage, PYO Sa , for combination phage and antibiotic treatment of Staphylococcus aureus infections. This K-like phage has a broad host range; all 83 tested clinical isolates of S.aureus tested were susceptible to PYO Sa . Because of the mode of action of PYO Sa , S. aureus is unlikely to generate classical receptor-site mutants resistant to PYO Sa ; none were observed in the 13 clinical isolates tested. PYO Sa kills S. aureus at high rates. On the downside, the results of our experiments and tests of the joint action of PYO Sa and antibiotics raise issues that must be addressed before PYO Sa is employed clinically. Despite the maintenance of the phage, PYO Sa does not clear populations of S. aureus . Due to the ascent of a phenotyically diverse array of small-colony variants following an initial demise, the bacterial populations return to densities similar to that of phage-free controls. Using a combination of mathematical modeling and in vitro experiments, we postulate and present evidence for a mechanism to account for the demise–resurrection dynamics of PYO Sa and S. aureus . Critically for phage therapy, our experimental results suggest that treatment with PYO Sa followed by bactericidal antibiotics can clear populations of S. aureus more effectively than the antibiotics alone.
关键词：phage therapy ; population dynamics ; Staphylococcus aureus