title: Engineering Modular Viral Scaffolds for Targeted Bacterial Population Editing.
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 accurately 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 inSaccharomyces cerevisiae. We used this technology to redirectEscherichia coliphage scaffolds to target pathogenicYersiniaandKlebsiellabacteria, and conversely,Klebsiellaphage scaffolds to targetE. coliby 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 that this approach will accelerate phage-biology studies and enable new technologies for bacterial population editing.
authors.affiliation: Department of Electrical Engineering & Computer Science and Department of Biological Engineering, Synthetic Biology Center, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ando
authors.affiliation: Department of Electrical Engineering & Computer Science and Department of Biological Engineering, Synthetic Biology Center, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Lemire
authors.affiliation: Department of Electrical Engineering & Computer Science and Department of Biological Engineering, Synthetic Biology Center, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Centre of Biological Engineering, University of Minho, Campus de Gualtar 4710-057, Braga, Portugal.
authors.forename: Diana P
authors.initials: DP
authors.lastname: Pires
authors.affiliation: Department of Electrical Engineering & Computer Science and Department of Biological Engineering, Synthetic Biology Center, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Lu