Engineering Modular Viral Scaffolds for Targeted Bacterial Population Editing
Engineering Modular Viral Scaffolds for Targeted Bacterial Population Editing
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DOI：
10.1016/j.cels.2015.08.013
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发表时间：
2015-09-23
期刊：
影响因子：
9.3
通讯作者：
Lu, Timothy K.
中科院分区：
文献类型：
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作者：
Ando, Hiroki;Lemire, Sebastien;Lu, Timothy K.
细菌是人类健康和疾病的核心，但现有的编辑微生物财团的工具是有限的。例如，广谱抗生素无法精确操纵细菌群落。噬菌体可以提供高度特异性的细菌靶向，但是仅用天然的噬菌体组装定义明确的噬菌体鸡尾酒可能是一个时间、劳动力和成本密集型的过程。在这里，我们提出了一种合成生物学策略，通过在酿酒酵母中改造噬菌体基因组来调节噬菌体宿主范围。我们使用这种技术将大肠杆菌噬菌体支架重定向到致病性耶尔森氏菌和克雷伯氏菌，反之，克雷伯氏菌噬菌体支架则靶向大肠杆菌。通过噬菌体尾部组分的模块交换，合成的病毒载体实现了对新目标细菌的有效杀灭，并用于选择性地从多物种细菌群落中去除细菌，其中混合物基于常见的病毒支架。我们设想这种方法加速噬菌体生物学研究，并实现细菌群体编辑的新技术。
Bacteria are central to human health and disease, but existing tools to edit microbial consortia are limited. For example, broad-spectrum antibiotics are unable to precisely manipulate bacterial communities. Bacteriophages can provide highly specific targeting of bacteria, but assembling well-defined phage cocktails solely with natural phages can be a time-, labor- and cost-intensive process. Here, we present a synthetic biology strategy to modulate phage host ranges by engineering phage genomes in Saccharomyces cerevisiae. We used this technology to redirect Escherichia coli phage scaffolds to target pathogenic Yersinia and Klebsiella bacteria, and conversely, Klebsiella phage scaffolds to target E. coli by modular swapping of phage tail components. The synthetic phages achieved efficient killing of their new target bacteria and were used to selectively remove bacteria from multi-species bacterial communities with cocktails based on common viral scaffolds. We envision this approach accelerating phage biology studies and enabling new technologies for bacterial population editing.