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用噬菌体疗法靶向粪肠球菌生物膜。

Targeting Enterococcus faecalis biofilms with phage therapy.

作者信息

Khalifa Leron, Brosh Yair, Gelman Daniel, Coppenhagen-Glazer Shunit, Beyth Shaul, Poradosu-Cohen Ronit, Que Yok-Ai, Beyth Nurit, Hazan Ronen

机构信息

Faculty of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel Department of Prosthodontics, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel.

Faculty of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel.

出版信息

Appl Environ Microbiol. 2015 Apr;81(8):2696-705. doi: 10.1128/AEM.00096-15. Epub 2015 Feb 6.

Abstract

Phage therapy has been proven to be more effective, in some cases, than conventional antibiotics, especially regarding multidrug-resistant biofilm infections. The objective here was to isolate an anti-Enterococcus faecalis bacteriophage and to evaluate its efficacy against planktonic and biofilm cultures. E. faecalis is an important pathogen found in many infections, including endocarditis and persistent infections associated with root canal treatment failure. The difficulty in E. faecalis treatment has been attributed to the lack of anti-infective strategies to eradicate its biofilm and to the frequent emergence of multidrug-resistant strains. To this end, an anti-E. faecalis and E. faecium phage, termed EFDG1, was isolated from sewage effluents. The phage was visualized by electron microscopy. EFDG1 coding sequences and phylogeny were determined by whole genome sequencing (GenBank accession number KP339049), revealing it belongs to the Spounavirinae subfamily of the Myoviridae phages, which includes promising candidates for therapy against Gram-positive pathogens. This analysis also showed that the EFDG1 genome does not contain apparent harmful genes. EFDG1 antibacterial efficacy was evaluated in vitro against planktonic and biofilm cultures, showing effective lytic activity against various E. faecalis and E. faecium isolates, regardless of their antibiotic resistance profile. In addition, EFDG1 efficiently prevented ex vivo E. faecalis root canal infection. These findings suggest that phage therapy using EFDG1 might be efficacious to prevent E. faecalis infection after root canal treatment.

摘要

噬菌体疗法已被证明在某些情况下比传统抗生素更有效,特别是在治疗多重耐药生物膜感染方面。本文的目的是分离一种抗粪肠球菌噬菌体,并评估其对浮游菌和生物膜培养物的疗效。粪肠球菌是许多感染中发现的重要病原体,包括心内膜炎和与根管治疗失败相关的持续性感染。粪肠球菌治疗的困难归因于缺乏根除其生物膜的抗感染策略以及多重耐药菌株的频繁出现。为此,从污水中分离出一种抗粪肠球菌和屎肠球菌的噬菌体,称为EFDG1。通过电子显微镜观察到了该噬菌体。通过全基因组测序(GenBank登录号KP339049)确定了EFDG1的编码序列和系统发育,表明它属于肌尾噬菌体科的Spounavirinae亚科,该亚科包括治疗革兰氏阳性病原体的有前景的候选噬菌体。该分析还表明EFDG1基因组不包含明显的有害基因。在体外评估了EFDG1对浮游菌和生物膜培养物的抗菌疗效,结果表明它对各种粪肠球菌和屎肠球菌分离株具有有效的裂解活性,无论其抗生素耐药谱如何。此外,EFDG1有效地预防了体外粪肠球菌根管感染。这些发现表明,使用EFDG1进行噬菌体疗法可能对预防根管治疗后的粪肠球菌感染有效。

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Targeting Enterococcus faecalis biofilms with phage therapy.用噬菌体疗法靶向粪肠球菌生物膜。
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