An expanded arsenal of immune systems that protect bacteria from phages

Millman, Adi; Melamed, Sarah; Leavitt, Azita; Doron, Shany; Bernheim, Aude; Hör, Jens; Garb, Jeremy; Béchon, Nathalie; Brandis, Alexander; Lopatina, Anna; Ofir, Gal; Hochhauser, Dina; Stokar-Avihail, Avigail; Tal, Nitzan; Sharir, Saar; Voichek, Maya; Erez, Zohar; Ferrer, Jose Lorenzo M.; Dar, Daniel; Kacen, Assaf; Amitai, Gil; Sorek, Rotem

doi:10.1016/j.chom.2022.09.017

Cited by 211 publications

(247 citation statements)

References 103 publications

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“…Of the total number of defense systems in cDHS1, Shedu, Type I RM and Type III RM were the most common immune systems found, with over one third belonging to RM (Figure 3B). We find that another large percentage of immune systems come from publications that used computational analysis of defense islands (2, 3, 22) (Figure 3B). We find at least one immune system in 83.7% of cDHS1 loci (Supplemental table 1), clearly demonstrating an immune functionality for cDHS1.…”

Section: Resultsmentioning

confidence: 95%

“…We call this anti-phage system, Shango. Shango was recently identified in immune islands in E. coli and modestly inhibited the replication of two different phages by ∼10-fold (22).…”

Section: Resultsmentioning

confidence: 99%

“…The systems published by Doron et al, in 2018 account for almost half of the systems found at cDHS2. During the preparation of this manuscript, another report with 21 new immune systems was published, including Shango (22). These systems account for roughly a quarter of the known immune systems in cDHS1 and cDHS2.…”

Section: Discussionmentioning

confidence: 99%

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Core Defense Hotspots withinPseudomonas aeruginosaare a consistent and rich source of anti-phage defense systems

Johnson

Laderman

Huiting

et al. 2022

Preprint

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Bacteria use a diverse arsenal of anti-phage immune systems, including CRISPR-Cas and restriction enzymes. Identifying the full defense repertoire of a given species is still challenging, however. Here, we developed a computational tool to broadly identify anti-phage systems, which was applied to >180,000 genomes available on NCBI, revealingPseudomonas aeruginosato possess the most diverse anti-phage arsenal of any species with >200 sequenced genomes. Using network analysis to identify the common neighbors of anti-phage systems, we surprisingly identified two highly conserved core defense hotspot loci (cDHS1 and cDHS2). Across more than 1,000 P. aeruginosa strains, cDHS1 is up to 224 kb (mean: 34 kb) with varied arrangements of at least 31 immune systems while cDHS2 has 24 distinct systems (mean: 15.4 kb). cDHS1/2 are present in mostP. aeruginosaisolates, in contrast to highly variable mobile DHSs. Most cDHS genes are of unknown function potentially representing new anti-phage systems, which we validated by identifying a novel anti-phage system (Shango) commonly encoded in cDHS1. Identification of core gene markers that flank immune islands could be a simple approach for immune system discovery and may represent popular landing spots for diverse MGEs carrying anti-phage systems.

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Section: Resultsmentioning

confidence: 95%

“…We call this anti-phage system, Shango. Shango was recently identified in immune islands in E. coli and modestly inhibited the replication of two different phages by ∼10-fold (22).…”

Section: Resultsmentioning

confidence: 99%

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Core Defense Hotspots withinPseudomonas aeruginosaare a consistent and rich source of anti-phage defense systems

Johnson

Laderman

Huiting

et al. 2022

Preprint

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“…Furthermore, while observations have been made on mixed chains of ubiquitin and ISG15, their physiological relevance is far less clear [88]. The recent discovery of ISG15 in bacterial immune defence may offer a simpler model system to interrogate some of these mechanisms [89]. Investigations on these aspects will not only provide fundamental insights, but may also prove useful in developing strategies to combat hyper-inflammation accompanying infection or autoimmune disorders.…”

Section: Discussionmentioning

confidence: 99%

ISG15 driven cellular responses to virus infection

Munnur

Banducci-Karp

Sanyal

2022

Biochemical Society Transactions

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One of the hallmarks of antiviral responses to infection is the production of interferons and subsequently of interferon stimulated genes. Interferon stimulated gene 15 (ISG15) is among the earliest and most abundant proteins induced upon interferon signalling, encompassing versatile functions in host immunity. ISG15 is a ubiquitin like modifier that can be conjugated to substrates in a process analogous to ubiquitylation and referred to as ISGylation. The free unconjugated form can either exist intracellularly or be secreted to function as a cytokine. Interestingly, ISG15 has been reported to be both advantageous and detrimental to the development of immunopathology during infection. This review describes recent findings on the role of ISG15 in antiviral responses in human infection models, with a particular emphasis on autophagy, inflammatory responses and cellular metabolism combined with viral strategies of counteracting them. The field of ISGylation has steadily gained momentum; however much of the previous studies of virus infections conducted in mouse models are in sharp contrast with recent findings in human cells, underscoring the need to summarise our current understanding of its potential antiviral function in humans and identify knowledge gaps which need to be addressed in future studies.

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“…In chordates, including humans, the first line of defense against infection relies on the steady-state expression of restriction factors, as well as on the interferon-driven upregulation of a panel of antiviral effectors termed interferon-stimulated genes (ISGs) (1). Prokaryotes implement diverse antiviral systems to thwart bacteriophages (phages), including restrictionmodification and CRISPR-Cas systems (2)(3)(4)(5). Each system may be composed of a unique gene or of multiple genes whose products act in concert.…”

Section: Mainmentioning

confidence: 99%

Conservation of antiviral systems across domains of life reveals novel immune mechanisms in humans

Cury

Mordret

Hernandez-Trejo

et al. 2022

Preprint

Self Cite

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Viral infection is a common threat to prokaryotic and eukaryotic life, which has resulted in the evolution of a myriad of antiviral systems. Some of these eukaryotic systems are thought to have evolved from prokaryotic antiphage proteins, with which they may display sequence and structural homology. Here, we show that homologs of recently discovered antiphage systems are widespread in eukaryotes. We demonstrate that such homologs can retain a function in immunity by unveiling that eukaryotic proteins of the anti-transposon piRNA pathway display domain homology with the antiphage system Mokosh. We further utilise this conservation to discover novel human antiviral genes related to the Eleos and Lamassu prokaryotic systems. We propose that comparative immunology across domains of life can be leveraged to discover immune genes in eukaryotes.

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An expanded arsenal of immune systems that protect bacteria from phages

Cited by 211 publications

References 103 publications

Core Defense Hotspots withinPseudomonas aeruginosaare a consistent and rich source of anti-phage defense systems

Core Defense Hotspots withinPseudomonas aeruginosaare a consistent and rich source of anti-phage defense systems

ISG15 driven cellular responses to virus infection

Conservation of antiviral systems across domains of life reveals novel immune mechanisms in humans

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