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DOI	10.1073/pnas.2008007118
	Evaluating the potential efficacy and limitations of a phage for joint antibiotic and phage therapy of Staphylococcus aureus infections
	Berryhill B.A.; Huseby D.L.; McCall I.C.; Hughes D.; Levin B.R.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	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, PYOSa, 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 PYOSa. Because of the mode of action of PYOSa, S. aureus is unlikely to generate classical receptor-site mutants resistant to PYOSa; none were observed in the 13 clinical isolates tested. PYOSa kills S. aureus at high rates. On the downside, the results of our experiments and tests of the joint action of PYOSa and antibiotics raise issues that must be addressed before PYOSa is employed clinically. Despite the maintenance of the phage, PYOSa 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 PYOSa and S. aureus. Critically for phage therapy, our experimental results suggest that treatment with PYOSa followed by bactericidal antibiotics can clear populations of S. aureus more effectively than the antibiotics alone. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Phage therapy; Population dynamics; Staphylococcus aureus
语种	英语
scopus关键词	antibiotic agent; antibiotic sensitivity; Article; bacterium isolate; controlled study; genetic variability; in vitro study; mathematical model; microarray analysis; nonhuman; phage therapy; priority journal; Staphylococcus aureus; Staphylococcus aureus infection
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180365
作者单位	Department of Biology, Emory University, Atlanta, GA 30322, United States; Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Uppsala, 751 23, Sweden
推荐引用方式 GB/T 7714	Berryhill B.A.,Huseby D.L.,McCall I.C.,et al. Evaluating the potential efficacy and limitations of a phage for joint antibiotic and phage therapy of Staphylococcus aureus infections[J],2021,118(10).
APA	Berryhill B.A.,Huseby D.L.,McCall I.C.,Hughes D.,&Levin B.R..(2021).Evaluating the potential efficacy and limitations of a phage for joint antibiotic and phage therapy of Staphylococcus aureus infections.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Berryhill B.A.,et al."Evaluating the potential efficacy and limitations of a phage for joint antibiotic and phage therapy of Staphylococcus aureus infections".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).