Engineering a dynamic, controllable infectivity switch in bacteriophage T7
Engineering a dynamic, controllable infectivity switch in bacteriophage T7
Abstract 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.
Huss Phil、Raman Srivatsan、Fernholz Mikayla、Chitboonthavisuk Chutikarn、Luo Chun Huai
Dept. of Biochemistry, Univ. of Wisconsin-Madison||Dept. of Bacteriology, Univ. of Wisconsin-Madison||Microbiology Doctoral Training Program, University of Wisconsin-MadisonDept. of Biochemistry, Univ. of Wisconsin-Madison||Dept. of Bacteriology, Univ. of Wisconsin-Madison||Dept. of Chemical & Biological Eng., Univ. of Wisconsin-MadisonDept. of Biochemistry, Univ. of Wisconsin-MadisonDept. of Biochemistry, Univ. of Wisconsin-Madison||Dept. of Bacteriology, Univ. of Wisconsin-Madison||Microbiology Doctoral Training Program, University of Wisconsin-MadisonDept. of Biochemistry, Univ. of Wisconsin-Madison||Dept. of Bacteriology, Univ. of Wisconsin-Madison
生物工程学分子生物学生物科学研究方法、生物科学研究技术
engineered bacteriophagephage switchligand-responsive phagesphage genome editing
Huss Phil,Raman Srivatsan,Fernholz Mikayla,Chitboonthavisuk Chutikarn,Luo Chun Huai.Engineering a dynamic, controllable infectivity switch in bacteriophage T7[EB/OL].(2025-03-28)[2025-04-29].https://www.biorxiv.org/content/10.1101/2021.08.23.457391.点此复制
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