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1997 年至 2014 年治疗性 PYO 噬菌体鸡尾酒的宏基因组分析。

Metagenomic Analysis of Therapeutic PYO Phage Cocktails from 1997 to 2014.

机构信息

Department of Bio and Health Informatics, Technical University of Denmark, Kemitorvet, Building 208, 2800 Kongens Lyngby, Denmark.

GoSeqIt ApS, Ved Klædebo 9, 2970 Hørsholm, Denmark.

出版信息

Viruses. 2017 Nov 3;9(11):328. doi: 10.3390/v9110328.

DOI:10.3390/v9110328
PMID:29099783
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5707535/
Abstract

Phage therapy has regained interest in recent years due to the alarming spread of antibiotic resistance. Whilst phage cocktails are commonly sold in pharmacies in countries such as Georgia and Russia, this is not the case in western countries due to western regulatory agencies requiring a thorough characterization of the drug. Here, DNA sequencing of constituent biological entities constitutes a first step. The pyophage (PYO) cocktail is one of the main commercial products of the Georgian Eliava Institute of Bacteriophage, Microbiology and Virology and is used to cure skin infections. Since its first production in the 1930s, the composition of the cocktail has been periodically modified to add phages effective against emerging pathogenic strains. In this paper, we compared the composition of three PYO cocktails from 1997 (PYO97), 2000 (PYO2000) and 2014 (PYO2014). Based on next generation sequencing, de novo assembly and binning of contigs into draft genomes based on tetranucleotide distance, thirty and twenty-nine phage draft genomes were predicted in PYO97 and PYO2014, respectively. Of these, thirteen and fifteen shared high similarity to known phages. Eleven draft genomes were found to be common in the two cocktails. One of these showed no similarity to publicly available phage genomes. Representatives of phages targeting , , , , and were found in both cocktails. Finally, we estimated larger overlap of the PYO2000 cocktail to PYO97 compared to PYO2014. Using next generation sequencing and metagenomics analysis, we were able to characterize and compare the content of PYO cocktails separated by 17 years in time. Even though the cocktail composition is upgraded every six months, we found it to remain relatively stable over the years.

摘要

噬菌体疗法近年来由于抗生素耐药性的惊人传播而重新引起关注。虽然噬菌体制剂鸡尾酒在格鲁吉亚和俄罗斯等国家的药店中很常见,但在西方国家并非如此,因为西方监管机构要求对药物进行彻底的特性描述。在这里,构成生物实体的 DNA 测序构成了第一步。PYO 鸡尾酒是格鲁吉亚 Eliava 噬菌体、微生物学和病毒学研究所的主要商业产品之一,用于治疗皮肤感染。自 1930 年代首次生产以来,该鸡尾酒的成分已定期修改,以添加针对新出现的致病菌株有效的噬菌体。在本文中,我们比较了 1997 年(PYO97)、2000 年(PYO2000)和 2014 年(PYO2014)的三种 PYO 鸡尾酒的组成。基于下一代测序,基于四核苷酸距离将重叠序列组装成草图基因组,并对其进行分类,在 PYO97 和 PYO2014 中分别预测了三十和二十九种噬菌体草图基因组。其中,十三和十五种与已知噬菌体具有高度相似性。在这两种鸡尾酒中发现了十一种共同的草图基因组。其中一种与公开的噬菌体基因组没有相似性。针对 、 、 、 和 的噬菌体的代表在两种鸡尾酒中都有发现。最后,我们估计 PYO2000 鸡尾酒与 PYO97 的重叠比 PYO2014 更大。使用下一代测序和宏基因组学分析,我们能够对经过 17 年时间分离的 PYO 鸡尾酒进行特征描述和比较。尽管鸡尾酒的成分每六个月升级一次,但我们发现多年来它仍然相对稳定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a6/5707535/f645b71b962e/viruses-09-00328-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a6/5707535/af40355577fb/viruses-09-00328-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a6/5707535/edce0bef6ec2/viruses-09-00328-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a6/5707535/039e4de6ea09/viruses-09-00328-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a6/5707535/0fd592fd7731/viruses-09-00328-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a6/5707535/f645b71b962e/viruses-09-00328-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a6/5707535/af40355577fb/viruses-09-00328-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a6/5707535/edce0bef6ec2/viruses-09-00328-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a6/5707535/039e4de6ea09/viruses-09-00328-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a6/5707535/0fd592fd7731/viruses-09-00328-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a6/5707535/f645b71b962e/viruses-09-00328-g004.jpg

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