Transcriptional repressors play an important role in regulating phage genomes. Here, we examined how synthetic regulation based on repressors can be to create a dynamic, controllable infectivity switch in bacteriophage T7. We engineered T7 by replacing a large region of the early phage genome with combinations of ligand-responsive promoters and ribosome binding sites (RBS) designed to control the phage RNA polymerase. Phages with the engineered switch showed virulence comparable to wildtype when not repressed, indicating the phage can be engineered without a loss of fitness. When repressed, the most effective switch used a TetR promoter and a weak RBS, resulting in a two-fold increase in latent period (time to lyse host) and change in phage titer. Further, phage activity could be tuned by varying inducer concentrations. Our study provides a proof of concept for a simple circuit for user control over phage infectivity.

中文翻译：

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在噬菌体 T7 中设计动态、可控的感染性开关

转录抑制因子在调节噬菌体基因组中发挥重要作用。在这里，我们研究了基于阻遏物的合成调节如何在噬菌体 T7 中创建动态、可控的感染性开关。我们通过用配体响应启动子和核糖体结合位点 (RBS) 的组合替换早期噬菌体基因组的一个大区域来设计 T7，旨在控制噬菌体 RNA 聚合酶。具有工程开关的噬菌体在不受抑制时表现出与野生型相当的毒力，表明可以对噬菌体进行工程改造而不会损失适应性。当被抑制时，最有效的开关使用 TetR 启动子和弱 RBS，导致潜伏期（裂解宿主的时间）和噬菌体滴度增加两倍。此外，噬菌体活性可以通过改变诱导剂浓度来调整。