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噬菌体鸡尾酒疗法及噬菌体与抗生素协同作用有望成为控制多重耐药性尿路致病性大肠杆菌的传统抗生素替代方案。

Bacteriophage cocktail and phage antibiotic synergism as promising alternatives to conventional antibiotics for the control of multi-drug-resistant uropathogenic Escherichia coli.

作者信息

Malik Shikha, Nehra Kiran, Rana J S

机构信息

Department of Biotechnology, Deenbandhu Chhotu Ram University of Science & Technology, Murthal, 131039, Sonipat, Haryana, India.

Department of Biotechnology, Deenbandhu Chhotu Ram University of Science & Technology, Murthal, 131039, Sonipat, Haryana, India.

出版信息

Virus Res. 2021 Sep;302:198496. doi: 10.1016/j.virusres.2021.198496. Epub 2021 Jun 25.

DOI:10.1016/j.virusres.2021.198496
PMID:34182014
Abstract

Infections related to antibiotic resistant bacteria are accelerating on a global scale, and hence to encounter this problem in case of urinary tract infections; bacteriophages were isolated for biocontrol of multi-drug resistant (MDR) uropathogenic Escherichia coli (UPECs) isolates. Four lytic phages were purified, characterized, and evaluated for their effectiveness in the form of cocktail and in synergy with antibiotics. Morphological features and other life cycle specifications of phages revealed that two phages Escherichia phage FS11 and Escherichia phage FS17 belonged to Myoviridae and the other two phages Escherichia phage PS8 and Escherichia phage PS6 belonged to Siphoviridae family of order Caudovirales. One step growth curve analysis demonstrated that phage FS11 and phage FS17 had latent time of 24 min and 26 min, and a burst size of ~121 and 98 phage particles/ cell respectively; while for phage PS8 and phage PS6, the latent time was 42 min and 35 min, and the burst size was 87 and 78 particles/ cell, respectively; depicting the lytic nature of phages. The use of all four phages together in the form of a cocktail resulted into a considerable enhancement in the lytic ability; the phage cocktail lysed 86.7% of the clinical isolates, compared to lysis in the range of 50%-66% by individual phages. Studies on in vitro evaluation of phage-antibiotic combinations revealed synergism between antibiotics and the phage cocktail (phage PS6 and phage FS17), wherein the phage cocktail was observed to efficiently inhibit the strains in the presence of sub-lethal doses of antibiotics. The study thus concludes that the use of multiple phages and phage-antibiotic combinations could prove beneficial in the era of rapidly increasing drug-resistant strains.

摘要

与抗生素耐药细菌相关的感染正在全球范围内加速蔓延,因此为了解决尿路感染中的这一问题,分离出了噬菌体用于对多重耐药(MDR)尿路致病性大肠杆菌(UPEC)分离株进行生物防治。纯化、鉴定了四种裂解性噬菌体,并评估了它们以鸡尾酒形式以及与抗生素协同作用时的有效性。噬菌体的形态特征和其他生命周期特性表明,两种噬菌体——大肠杆菌噬菌体FS11和大肠杆菌噬菌体FS17属于肌尾噬菌体科,另外两种噬菌体——大肠杆菌噬菌体PS8和大肠杆菌噬菌体PS6属于有尾噬菌体目长尾噬菌体科。一步生长曲线分析表明,噬菌体FS11和噬菌体FS17的潜伏期分别为24分钟和26分钟,爆发量分别约为121和98个噬菌体颗粒/细胞;而对于噬菌体PS8和噬菌体PS6,潜伏期分别为42分钟和35分钟,爆发量分别为87和78个颗粒/细胞,这显示了噬菌体的裂解特性。将所有四种噬菌体以鸡尾酒形式一起使用,导致裂解能力有相当大的提高;噬菌体鸡尾酒裂解了86.7%的临床分离株,相比之下单个噬菌体的裂解率在50%-66%之间。噬菌体-抗生素组合的体外评估研究表明抗生素与噬菌体鸡尾酒(噬菌体PS6和噬菌体FS17)之间存在协同作用,其中观察到在亚致死剂量抗生素存在的情况下,噬菌体鸡尾酒能有效抑制菌株。因此,该研究得出结论,在耐药菌株迅速增加的时代,使用多种噬菌体和噬菌体-抗生素组合可能是有益的。

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