Biology and Genomics of an Historic Therapeutic Escherichia coli Bacteriophage Collection.
Biology and Genomics of an Historic Therapeutic Escherichia coli Bacteriophage Collection.
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DOI：
10.3389/fmicb.2017.01652
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发表时间：
2017
影响因子：
5.2
通讯作者：
Atterbury R
中科院分区：
文献类型：
--
作者：
Baig A;Colom J;Barrow P;Schouler C;Moodley A;Lavigne R;Atterbury R
我们对历史上收集的九个噬菌体进行了微生物学和基因组鉴定，这些噬菌体专门感染了K1大肠杆菌O18：K1：H7COLV+菌株。这些噬菌体是从污水中分离出来的，并在体内测试了它们在小鼠感染模型中治疗系统性大肠杆菌感染的有效性。这项研究的目的是确定共同的微生物和基因组特征，这些特征与这些噬菌体在体内研究中的表现密切相关。这些功能将允许在知情的情况下选择噬菌体作为治疗剂。透射电子显微镜显示，9个噬菌体中有6个是Podoviridae，其余3个是Siphopviridae。体内表现最好的四个噬菌体属于Podoviridae家族。在体外，这些噬菌体表现出很短的潜伏期和上升期。基因组测序结果表明，这6种病毒均属于链球病毒亚家族。在这些病毒中，有四个是同一物种的分离株(99%的同源性)，而与其他PODOV相比，有两个具有不同的基因组。噬菌体在体内表现中等至差，在体外表现出较长的潜伏期和上升期。这三种病毒中有两种彼此关系密切(99%的同源性)，但都与格恩赛病毒亚家族有关。两种噬菌体的基因组序列比较表明，编码依赖于DNA的RNA聚合酶的基因只存在于复制周期较快的噬菌体中，这可能是它们在体内表现较好的原因。这些数据定义了微生物、基因组和体内特性的组合，允许对原始体内数据进行更合理的评估，并为未来噬菌体治疗试验的噬菌体选择铺平道路。
We have performed microbiological and genomic characterization of an historic collection of nine bacteriophages, specifically infecting a K1 E. coli O18:K1:H7 ColV+ strain. These phages were isolated from sewage and tested for their efficacy in vivo for the treatment of systemic E. coli infection in a mouse infection model by. The aim of the study was to identify common microbiological and genomic characteristics, which co-relate to the performance of these phages in in vivo study. These features will allow an informed selection of phages for use as therapeutic agents. Transmission electron microscopy showed that six of the nine phages were Podoviridae and the remaining three were Siphoviridae. The four best performing phages in vivo belonged to the Podoviridae family. In vitro, these phages exhibited very short latent and rise periods in our study. In agreement with their microbiological profiles, characterization by genome sequencing showed that all six podoviruses belong to the Autographivirinae subfamily. Of these, four were isolates of the same species (99% identity), whereas two had divergent genomes compared to other podoviruses. The Siphoviridae phages, which were moderate to poor performers in vivo, exhibited longer latent and rise periods in vitro. Two of the three siphoviruses were closely related to each other (99% identity), but all can be associated with the Guernseyvirinae subfamily. Genome sequence comparison of both types of phages showed that a gene encoding for DNA-dependent RNA polymerase was only present in phages with faster replication cycle, which may account for their better performance in vivo. These data define a combination of microbiological, genomic and in vivo characteristics which allow a more rational evaluation of the original in vivo data and pave the way for the selection of phages for future phage therapy trails.