Bacterial NLR-related proteins protect against phage

Kibby, Emily; Conte, Amy N.; Burroughs, A. Maxwell; Nagy, Toni A.; Vargas, José A.; Aravind, L.; Whiteley, Aaron T.

doi:10.1101/2022.07.19.500537

Cited by 23 publications

(40 citation statements)

References 83 publications

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“…2B, Table S4). In addition to its presence within CBASS systems, we found this domain in the N-terminus of diverse genes of the Avs family 5,6 . These genes represent a large family of immune proteins that are the likely ancestors of human and plant NODlike receptors (NLRs) and inflammasomes 5,6 .…”

Section: A Specialized Immune Nucleosidase Domain Functions In Multip...mentioning

confidence: 76%

A conserved family of immune effectors cleaves cellular ATP upon viral infection

Rousset

Yirmiya

Nesher

et al. 2023

Preprint

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During viral infection, cells can deploy immune strategies that deprive viruses of molecules essential for their replication. In this study, we report a family of immune effectors in bacteria which, in response to phage infection, degrade cellular ATP and dATP by cleaving the N-glycosidic bond between the adenine and sugar moieties. These ATP nucleosidase effectors are widely distributed within multiple bacterial defense systems including CBASS, prokaryotic argonautes and NLR-like proteins, and we show that degradation of (d)ATP during infection halts phage propagation and aborts infection. By analyzing homologs of the immune ATP nucleosidase domain, we discover and characterize Detocs, a new family of bacterial defense systems with a two-component phosphotransfer signaling architecture. The immune ATP nucleosidase domain is also encoded within a diverse set of eukaryotic proteins that have immune-like architectures, and we show biochemically that these eukaryotic homologs preserve the ATP nucleosidase activity. Our findings suggest that ATP and dATP degradation is a cell-autonomous innate immune strategy conserved across the tree of life.

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Section: A Specialized Immune Nucleosidase Domain Functions In Multip...mentioning

confidence: 76%

A conserved family of immune effectors cleaves cellular ATP upon viral infection

Rousset

Yirmiya

Nesher

et al. 2023

Preprint

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“…Depletion of cellular dNTPs is a conserved antiviral strategy also found in eukaryotes, demonstrating a clear link between prokaryotic and eukaryotic immunity (20). Indeed, a striking characteristic that has emerged from recent studies is the evolutionary relatedness between many anti-phage systems and innate immune mechanisms in plants and animals (12,13,18,(21)(22)(23)(24)(25). Additional examples of bacterial anti-phage defense systems that are ancestors of eukaryotic immunity are represented by the viperins, gasdermins, NLR-related anti-phage systems, Toll/IL-1 receptor (TIR) domains (carried by the Thoeris system) and the bacterial cyclic oligonucleotide-based signalling system (CBASS) (12,13,18,(21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

Shield co-opts an RmuC domain to mediate phage defence acrossPseudomonasspecies

Macdonald

Strahl

Blower

et al. 2022

Preprint

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Competitive bacteria-bacteriophage interactions have resulted in the evolution of a plethora of bacterial defense systems preventing phage propagation. In recent years, computational and bioinformatic approaches have underpinned the discovery of numerous novel bacterial defense systems. Anti-phage systems are frequently encoded together in genomic loci termed defense islands. Here we report the identification and characterisation of a novel anti-phage system, which we have termed Shield, that forms part of the Pseudomonas defensive arsenal. The Shield system comprises a membrane-bound protein, ShdA, harboring an RmuC domain. Heterologous production of ShdA alone is sufficient to mediate bacterial immunity against a panel of phages. We show that ShdA homologues can degrade phage DNA in vitro and, when expressed in a heterologous host, can alter the organisation of chromosomal DNA to a nucleoid structure. Further analysis reveals that Shield can be divided into four subtypes, three of which contain additional components that in some cases can modulate the activity of ShdA and/or provide additional lines of phage defence. Collectively, our results identify a new player within the Pseudomonas bacterial immunity arsenal that displays a novel mechanism of protection, and reveals a surprising role of RmuC domains in phage defence.

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“…For instance, Thoeris TIRs generate immune signals, while other TIRs act as executioners that simply deplete NAD + (Burroughs et al, 2015; Doron et al, 2018; Hogrel et al, 2022; Koopal et al, 2022; Morehouse et al, 2022). Recently, NLR-like immune proteins were reported in prokaryotes, and certain unicellular algae encode TIR-NB-LRR proteins (Sun et al, 2014; Shao et al, 2019; Kibby et al, 2022). Evolution adapts existing genetic modules into new roles, and whether plant TIR-pathways can be directly traced to particular bacterial or unicellular eukaryote lineages remains an open question (Gao et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Plant and prokaryotic TIR domains generate distinct cyclic ADPR NADase products

Bayless

Chen

Ogden

et al. 2022

Preprint

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Toll/interleukin-1 receptor (TIR) domain proteins function in cell death and immunity. In plants and bacteria, TIR domains are enzymes that produce isomers of cyclic ADPR (cADPR) as putative immune signaling molecules. The identity and functional conservation of cADPR isomer signals is unclear. A previous report found that a plant TIR could cross activate the prokaryotic Thoeris TIR-immune system, suggesting the conservation of plant and prokaryotic TIR-immune signals. Here, we generate auto-active Thoeris TIRs and test the converse hypothesis: do prokaryotic Thoeris TIRs also cross-activate plant TIR immunity? Using in planta and in vitro assays, we find that Thoeris and plant TIRs generate overlapping sets of cADPR isomers, and further clarify how plant and Thoeris TIRs activate the Thoeris system via producing 3'cADPR. This study demonstrates that the TIR-signaling requirements for plant and prokaryotic immune systems are distinct and that TIRs across kingdoms generate a diversity of small molecule products.

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Bacterial NLR-related proteins protect against phage

Cited by 23 publications

References 83 publications

A conserved family of immune effectors cleaves cellular ATP upon viral infection

A conserved family of immune effectors cleaves cellular ATP upon viral infection

Shield co-opts an RmuC domain to mediate phage defence acrossPseudomonasspecies

Plant and prokaryotic TIR domains generate distinct cyclic ADPR NADase products

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