Engineering Modular Viral Scaffolds for Targeted Bacterial Population Editing
By Hiroki Ando, S. Lemire, D. Pires, Timothy K. Lu. 2015
387 citations recorded by the source corpus.
Bacteria are central to human health and disease, but the tools available for modulating and editing bacterial communities are limited. New technologies for tuning microbial populations would facilitate the targeted manipulation of the human microbiome and treatment of bacterial infections. For example, antibiotics are often broad spectrum in nature and cannot be used to accurately manipulate bacterial communities. Bacteriophages can provide highly specific targeting of bacteria, but relying solely on natural phage isolation strategies to assemble well-defined and uniform phage cocktails that are amenable to engineering can be a time-consuming and labor-intensive process. Here, we present a synthetic-biology strategy to modulate phage host ranges by manipulating phage genomes in Saccharomyces cerevisiae. We used this technology to swap multiple modular phage tail components and demonstrated that Escherichia coli phage scaffolds can be redirected to target pathogenic Yersinia and Klebsiella bacteria, and conversely, Klebsiella phage scaffolds can be redirected to target E. coli. The synthetic phages achieved multiple orders-of-magnitude killing of their new target bacteria and were used to selectively remove specific bacteria from multi-species bacterial communities. We envision that this approach will accelerate the study of phage biology, facilitate the tuning of phage host ranges, and enable new tools for microbiome engineering and the treatment of infectious diseases.
Subfields: Ecology, Genetics, Molecular Biology
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Citations in the corpus
- Molecular and Evolutionary Determinants of Bacteriophage Host Range. (2019, background): “Nevertheless, the fact that merely exchanging the tail fibre of phage T3 with that of Yersinia phage R resulted in T3 gaining the ability to infect the phage R host Yersinia tuberculosis shows the potential of bioengineering the RBP for host-range expansion [46].”
- Engineering Phage Host-Range and Suppressing Bacterial Resistance through Phage Tail Fiber Mutagenesis (2019, positive): “Each tail fiber is composed of a homotrimer of the gene 17 product, gp17, which we have previously identified the carboxyl-terminal, 450–553 amino acid globular domain or the ‘‘tip’’ of gp 17 as a determinant for host specificity (Ando et al., 2015).”
- Reprogramming Bacteriophage Host Range through Structure-Guided Design of Chimeric Receptor Binding Proteins. (2019, background): “Platform technologies that enable more systematic hostrange programming through exchange of specificity determinants have previously been established for phages that infect Gram-negative bacteria (Ando et al., 2015; Yosef et al., 2017; Yehl et al., 2019).”