4.5 Article

A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome

Journal

NATURE MICROBIOLOGY
Volume 7, Issue 10, Pages 1568-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41564-022-01219-4

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Funding

  1. National Institutes of Health, NIGMS [5F32 GM139231-02]
  2. Howard Hughes Medical Institute
  3. MIT-Skoltech

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The study identified numerous new candidate defense systems in E. coli using an experimental selection scheme, demonstrating that intact prophages and mobile genetic elements are primary reservoirs and distributors of defense systems.
The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. Here the authors use 71 E. coli strains to generate a fosmid library that is experimentally tested for anti-phage activity and find dozens of new candidate defence systems, many of which are carried on prophage or mobile genetic elements.

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