Phages and their satellites encode hotspots of antiviral systems

Rousset, François; Depardieu, Florence; Miele, Solange; Dowding, Julien; Laval, Anne-Laure; Lieberman, Erica; Garry, Daniel J.; Rocha, Eduardo P. C.; Bernheim, Aude; Bikard, David

doi:10.1016/j.chom.2022.02.018

Cited by 158 publications

(242 citation statements)

References 107 publications

Supporting

Mentioning

227

Contrasting

Order By: Relevance

“…Systems from the expanded family of Lamassu are found in ∼10% of the bacterial and archaeal genomes in our set (Table S7). Members of this family were previously detected in regions within prophage genomes that form hotspots for bacterial immune systems (Rousset et al, 2022), further supporting a general role in defense. As the lmuA gene frequently encodes an effector domain that is known to execute abortive infection in other defense systems, we hypothesize that the SMC-containing LmuB protein is responsible for the recognition of the invading phage, as was also previously suggested in other studies (Jaskólska et al, 2022; Krishnan et al, 2020).…”

Section: Resultsmentioning

confidence: 77%

“…These studies relied on the tendency of defense systems to co-localize on bacterial and archaeal genomes, forming so called “defense islands” (Makarova et al, 2011). Systematic analyses of defense islands in tens of thousands of microbial genomes (Doron et al, 2018; Gao et al, 2020; Rousset et al, 2022) have led to the discovery of several dozens of new defense systems exhibiting a variety of defensive mechanisms. These include systems that utilize second messenger signaling to mediate defense (Cohen et al, 2019; Ofir et al, 2021; Tal et al, 2021a; Whiteley et al, 2019), systems that produce antiviral molecules (Bernheim et al, 2021; Kever et al, 2021; Kronheim et al, 2018), and systems that rely on reverse transcription of small RNAs as part of the defensive machinery (Gao et al, 2020; Millman et al, 2020a).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An expanding arsenal of immune systems that protect bacteria from phages

Millman

Melamed

Leavitt

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Bacterial anti-phage defense systems are frequently clustered in microbial genomes, forming defense islands. This genomic property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms in bacteria is still unknown. In this study we report the discovery of 21 new defense systems that protect bacteria from phages, based on computational genomic analyses and phage infection experiments. We find multiple systems with protein domains known to be involved in eukaryotic anti-viral immunity, including ISG15-like proteins, dynamin-like proteins, and SEFIR domains, and show that these domains participate in bacterial defense against phages. Additional systems include protein domains predicted to manipulate DNA and RNA molecules, as well as multiple toxin-antitoxin systems shown here to function in anti-phage defense. The systems we discovered are widely distributed in bacterial and archaeal genomes, and in some bacteria form a considerable fraction of the immune arsenal. Our data substantially expand the known inventory of defense systems utilized by bacteria to counteract phage infection.

show abstract

Section: Resultsmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

An expanding arsenal of immune systems that protect bacteria from phages

Millman

Melamed

Leavitt

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Only 13 of these 63 hotspots contain previously known defense systems, and most genes are annotated as hypothetical. These findings suggest than not only do P2 prophages encode a rich diversity of anti-phage proteins 25 , but that P2 defense hotspots make up a significant fraction of the immune landscape in E. coli (Fig. 4b).…”

Section: Resultsmentioning

confidence: 91%

“…This location has been previously found to harbor the defense systems tin and old , the former of which was also identified in our screen against λ vir 24 (Table S1). More recently, this location was found to encode a wide array of previously uncharacterized defense systems 25 . We also observed a second defense-enriched locus in P2-like phages, which contained three of the systems discovered here, and the previously identified defense gene fun in the P2 reference genome 24 (Fig.…”

Section: Resultsmentioning

confidence: 97%

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

Vassallo

Doering

Littlehale

et al. 2022

Preprint

View full text Add to dashboard Cite

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.

show abstract

“…Recent works showed that mobile genetic elements are hotspots for anti-phage defense systems (Rousset et al , 2022; Bernheim & Sorek, 2019; Johnson et al , 2022), and that T6SS effectors often reside in mobile elements (Salomon et al , 2015; Jana et al , 2019). A previous report also indicated that T6SS components, such as Hcp and VgrG, are encoded on excisable pathogenicity islands that also contain CRISPR-Cas systems (Carpenter et al , 2017).…”

Section: Discussionmentioning

confidence: 99%

A DNase T6SS effector requires its MIX domain for secretion

Fridman

Jana

Ben-Yaakov

et al. 2022

Preprint

View full text Add to dashboard Cite

Bacteria use diverse classes of secreted polymorphic toxins to outcompete bacterial rivals. The MIX domain defines a widespread class of polymorphic type VI secretion system (T6SS) effectors, many of which are horizontally shared. Although several MIX-effectors have been investigated, the role of the MIX domain and the activity of many fused toxin domains remain unknown. Here, we use the Vibrio parahaemolyticus MIX-effector VPA1263 to demonstrate that MIX is necessary for T6SS-mediated secretion; however, we find that it is dispensable for interaction with the secreted T6SS tail tube component, VgrG. We also identify a C-terminal HNH nuclease toxin domain in VPA1263, and we demonstrate that it functions as a DNase during interbacterial competition. Finally, we identify variants of the genomic island containing vpa1263 in various vibrios, each carrying a different cargo of antibacterial T6SS effectors or anti-phage defense systems. We propose that these genomic islands are hotspots for bacterial defensive weapons.

show abstract

Phages and their satellites encode hotspots of antiviral systems

Cited by 158 publications

References 107 publications

An expanding arsenal of immune systems that protect bacteria from phages

An expanding arsenal of immune systems that protect bacteria from phages

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

A DNase T6SS effector requires its MIX domain for secretion

Contact Info

Product

Resources

About