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噬菌体治疗奶牛乳腺炎金黄色葡萄球菌的体外与体内评估。

In vitro and in vivo assessment of phage therapy against Staphylococcus aureus causing bovine mastitis.

机构信息

Bacteriology, Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine and Institute for Fundamental and Applied Research in Animals and Health (FARAH), University of Liège, Quartier Vallée 2, Avenue Cureghem 6, B-4000 Liège, Belgium.

Department of Food Safety and Infection Biology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P.O. Box 5003, 1432 Ås, Norway.

出版信息

J Glob Antimicrob Resist. 2020 Sep;22:762-770. doi: 10.1016/j.jgar.2020.06.020. Epub 2020 Jul 6.

Abstract

OBJECTIVE

The aim of this study was to assess the efficacy of lytic bacteriophages on Staphylococcus aureus causing bovine mastitis, by in vitro and in vivo assays using Galleria mellonella and murine mastitis models.

METHODS

Between May and December 2016, ten S. aureus (five methicillin-resistant and five methicillin-sensitive) isolates were isolated from milk samples of cattle with mastitis in Belgium and Norway. The isolates were assessed in vitro for their susceptibility to four lytic bacteriophages (Romulus, Remus, ISP and DSM105264) and subsequently in vivo in G. mellonella larvae and in murine mastitis model.

RESULTS

Romulus, Remus and ISP showed a lytic activity against the S. aureus isolates in vitro. A larvae survival rate below 50% was observed at 4 days post-inoculation (DPI) in the groups infected with a methicillin-sensitive S. aureus isolate and treated with these three phages in vivo. An incomplete recovery of the mouse mastitis was observed at 48h post-inoculation (HPI) in the groups infected and treated with the ISP phage in vivo CONCLUSIONS: The observations are much more pronounced statistically between the infected- phosphate buffered saline (PBS)-treated and infected-phage-treated groups in G. mellonella and the murine mastitis model demonstrating an effect of the phages against S. aureus associated with bovine mastitis.

摘要

目的

本研究通过使用家蚕和小鼠乳腺炎模型的体外和体内试验,评估裂解噬菌体对引起牛乳腺炎的金黄色葡萄球菌的疗效。

方法

2016 年 5 月至 12 月期间,从比利时和挪威患有乳腺炎的奶牛的牛奶样本中分离出 10 株金黄色葡萄球菌(5 株耐甲氧西林和 5 株耐甲氧西林敏感)。评估这些分离株对四种裂解噬菌体(Romulus、Remus、ISP 和 DSM105264)的体外敏感性,随后在体内的家蚕幼虫和小鼠乳腺炎模型中进行评估。

结果

Romulus、Remus 和 ISP 对金黄色葡萄球菌分离株在体外表现出裂解活性。在体内感染耐甲氧西林敏感金黄色葡萄球菌分离株并接受这三种噬菌体治疗的组中,在接种后 4 天(DPI)观察到幼虫存活率低于 50%。在体内感染并接受 ISP 噬菌体治疗的组中,在接种后 48 小时(HPI)观察到小鼠乳腺炎不完全恢复。

结论

在体内的家蚕和小鼠乳腺炎模型中,感染磷酸盐缓冲盐水(PBS)处理组与感染噬菌体处理组之间的观察结果在统计学上更为明显,证明噬菌体对与牛乳腺炎相关的金黄色葡萄球菌具有作用。

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