Jun 15, 2015

Engineering Modular Viral Scaffolds for Targeted Bacterial Population Editing

BioRxiv : the Preprint Server for Biology
Hiroki AndoTimothy K Lu

Abstract

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 fr...Continue Reading

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Mentioned in this Paper

Isolation Procedure
Study
Strategy
Genome
Saccharomyces cerevisiae allergenic extract
Antibiotic throat preparations
Pathogenic Organism
Antifungal Antibiotics, Topical
Bacteriophages
Yersinia <bacteria>

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