A host of armor: Prokaryotic immune strategies against mobile genetic elements

Mayo-Muñoz, David; Pinilla‐Redondo, Rafael; Birkholz, Nils; Fineran, Peter C.

doi:10.1016/j.celrep.2023.112672

Cited by 42 publications

(25 citation statements)

References 201 publications

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“… Immune systems are integral to survival against viral infection. Recently, dozens of new anti-viral systems have been characterized in bacteria 1 . Some of these systems are present in eukaryotes and appear to have originated in prokaryotes.…”

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confidence: 99%

Asgard archaea defense systems and their roles in the origin of immunity in eukaryotes

Leao,

Little,

Appler

et al. 2023

Preprint

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Immune systems are integral to survival against viral infection. Recently, dozens of new anti-viral systems have been characterized in bacteria1. Some of these systems are present in eukaryotes and appear to have originated in prokaryotes. However, little is known about these defense mechanisms in archaea. Here, we identified 2,610 complete defense systems in archaea related to eukaryotes, the Asgardarchaeota2. These comprise 89 unique systems, including argonaute, NLR, mokosh, viperin, lassamu, and CBASS. Asgard viperin (asVip) and argonaute (asAgo) proteins are present at high frequencies compared to bacteria and have structural homology to eukaryotes. Phylogenetic analyses revealed asVips are ancestral eukaryotic proteins. Heterologous expression of asVips in bacteria, including the lineage closest to eukaryotes, Hodarchaeales, showed robust anti-phage activity. Eukaryotic-and bacterial-argonaute proteins appear to have originated in the Asgardarchaeota, and have ancient structural characteristics. AsAgos appear to have argonaute-PIWI domains which are key components of the RNA interference (RNAi) in eukaryotes. Characterization of hundreds of new defense systems in the Asgardarchaeota revealed these archaea played important roles in the innovation of viral protection in eukaryotes. Given their relationship to eukaryotes, these defense systems may have applications in biomedicine and biotechnology.

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confidence: 99%

Asgard archaea defense systems and their roles in the origin of immunity in eukaryotes

Leao,

Little,

Appler

et al. 2023

Preprint

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“…Diverse antiviral defence systems have evolved in bacteria and archaea that defend them against phages, archaeal viruses and other mobile genetic elements (MGEs) (Georjon and Bernheim, 2023;Mayo-Muñoz et al, 2023). The protein domains associated with defence are wide-ranging and are often also found in other conserved cellular systems, complicating in silico discovery of new defence systems based on sequence alone.…”

Section: Introductionmentioning

confidence: 99%

New antiviral defences are genetically embedded within prokaryotic immune systems

Payne,

Hughes,

Fineran

et al. 2024

Preprint

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Bacteria and archaea typically have multiple defence systems that protect them against viral predation. Recently, many new defence systems have been discovered, yet the full scope of the prokaryotic pan-immune system remains to be determined. In this study, we observed that many multi-gene defence systems have additional genes nested or "embedded" within them. Based on this observation, we present a new approach to predict new defence systems, where defence function of uncharacterised genes is inferred based on their genetic embedding in known defence systems. Applying this "guilt-by-embedding" method, we identified and confirmed anti-phage function for seven defence systems and predicted 145 additional candidates. Our findings expand the known immune repertoire of prokaryotes, provide a wealth of new systems for future functional studies, and demonstrate a simple, efficient approach to identify new antiviral defences.

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“…For example, several anti-phage systems harbour a Toll/IL-1 receptor (TIR) domain 4,5,12,13 . In the Thoeris system this domain is used for the production of the isomer of cyclic adenosine 5'-diphosphate-ribose (cADPR) signalling molecule whereas in other instances TIR domains can harbour NADase activity that leads to impaired survival of phage-infected cells 1,4,12,14 . The Bil system represents another clear example wherein innate immunity pathways first evolved in bacteria.…”

Section: Introductionmentioning

confidence: 99%

Multi-conflict islands are a widespread trend withinSerratiaspp

Cummins,

Garrett,

Blower

et al. 2024

Preprint

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Bacteria carry numerous anti-phage systems in 'defence islands' or hotspots. Recent studies have delineated the content and boundaries of these islands in various species, revealing instances of islands that encode additional factors, including antibiotic resistance, stress genes, Type VI Secretion System (T6SS)-dependent effectors, and virulence factors. Our study identifies three defence islands in the Serratia genus with a mixed cargo of anti-phage systems, virulence factors and different types of anti-bacterial modules, revealing a widespread trend of co-accumulation that extends beyond T6SS-dependent effectors to colicins and contact-dependent inhibition systems. We report the identification of four distinct anti-phage system/subtypes, including a previously unreported Toll/IL-1 receptor (TIR)-domain-containing system with population-wide immunity, and two loci co-opting a predicted T6SS-related protein for phage defence. This study enhances our understanding of the protein domains that can be co-opted for phage defence and of the diverse combinations in which known anti-phage proteins can be assembled, resulting in a highly diversified anti-phage arsenal.

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A host of armor: Prokaryotic immune strategies against mobile genetic elements

Cited by 42 publications

References 201 publications

Asgard archaea defense systems and their roles in the origin of immunity in eukaryotes

Asgard archaea defense systems and their roles in the origin of immunity in eukaryotes

New antiviral defences are genetically embedded within prokaryotic immune systems

Multi-conflict islands are a widespread trend withinSerratiaspp

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