1. Engineering Modular Viral Scaffolds for Targeted Bacterial Population Editing
- Author
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Diana Priscila Penso Pires, Hiroki Ando, Sebastien Lemire, Timothy K. Lu, Universidade do Minho, MIT Synthetic Biology Center, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology. Research Laboratory of Electronics, Ando, Hiroki, Lemire, Sebastien, and Lu, Timothy K
- Subjects
Klebsiella ,Histology ,medicine.drug_class ,viruses ,Antibiotics ,Saccharomyces cerevisiae ,Bacterial population ,Computational biology ,Yersinia ,medicine.disease_cause ,Genome ,Article ,Pathology and Forensic Medicine ,Microbiology ,03 medical and health sciences ,Synthetic biology ,0302 clinical medicine ,medicine ,Microbiome ,Escherichia coli ,030304 developmental biology ,0303 health sciences ,Science & Technology ,biology ,Human microbiome ,Cell Biology ,biology.organism_classification ,Bacteria ,030215 immunology - Abstract
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., Defense Threat Reduction Agency (DTRA) (Grant HDTRA1-14-1-0007), National Institutes of Health (U.S.) (Grant 1DP2OD008435), National Institutes of Health (U.S.) (Grant 1P50GM098792), National Institutes of Health (U.S.) (Grant 1R01EB017755), Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies ( Contract W911NF-13-D-0001)
- Published
- 2016