Mapping the landscape of anti-phage defense mechanisms in the E. coli pangenome

Abstract

SummaryThe ancient, ongoing coevolutionary battle between bacteria and their viral predators, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Dozens of additional anti-phage systems have been identified based on their co-location within so-called defense islands, but whether these computational screens are exhaustive is unclear. Here, we developed an experimental selection scheme agnostic to genomic context to identify defense systems encoded in 71 diverse E. coli strains. Our results unveil 21 new and conserved defense systems, none of which were previously detected as enriched in defense islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defense systems in E. coli, with defense systems typically carried in specific locations, or hotspots. These hotspots in homologous prophages and mobile genetic elements encode dozens of additional, as-yet uncharacterized defense system candidates. Collectively, our findings reveal an extended landscape of antiviral immunity in E. coli and provide a generalizable approach for mapping defense systems in other species.

Accumulation of defense systems in phage-resistant strains of Pseudomonas aeruginosa

“…More recently, dozens of previously unknown anti-phage immune systems have been found. In most instances, they were identified on the basis of the observation that immune systems often cluster in defense islands (11)(12)(13)(14)(15)(16). The presence and composition of these defense islands vary among individual strains (4,15,17) and strongly contribute to phage-host coevolution in natural populations (1).…”

Arbitrium communication controls phage life-cycle through modulation of a bacterial anti-phage defense system

“…Notably, the ToxIN phage defense system also does not directly kill the cell and it would be interesting to study its possible effect on temperate phages 49 . Second, in contrast with the typical accessory nature of phage defense islands 15,16,19,20,52 , the MazEF system is part of the core genome of B. subtilis 53 . Third, we show here that MazEF can both serve as a defense system but also has a regulatory role.…”

“…Several toxin-antitoxin systems are known to act as anti-phage defense systems 19,[22][23][24][25][26][27][28] . MazEF of E. coli has also been attributed as such a defense system ( 47,48 , but c.f, 49 ) and a MazF homolog containing protein serve to defend against S. aureus phages 20 .…”

“…Phages face a variety of phage defense systems employed by their hosts [15][16][17][18][19][20] . These include both systems which directly restrict phages such as restriction-modification and CRISPR systems as well as a large cohort of abortive infection systems.…”

“…In the latter type, in response to phage infection, bacteria activate pathways which lead to cell stasis or cell death prior to the release of active virions 21 . Specifically, a variety of toxin-antitoxin systems have been shown to function as abortive infection systems, where phage infection leads to the formation of active toxin 19,[22][23][24][25][26][27][28] .…”