Short prokaryotic Argonaute systems trigger cell death upon detection of invading DNA

Koopal, Balwina; Potocnik, Ana; Mutte, Sumanth K.; Aparicio-Maldonado, Cristian; Lindhoud, Simon; Vervoort, Jacques; Brouns, Stan J. J.; Swarts, Daan C.

doi:10.1016/j.cell.2022.03.012

Cited by 134 publications

(225 citation statements)

References 86 publications

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“…CBASS systems were shown to be ancestral to the human cGAS-STING pathway (Cohen et al, 2019; Millman et al, 2020b; Morehouse et al, 2020; Whiteley et al, 2019; Ye et al, 2020), and evidence for eukaryotic acquisition of the antiviral protein viperin from archaea have been presented (Bernheim et al, 2021). Moreover, homologs of human immunity proteins such as gasdermins, Argonautes, and proteins with TIR domains were all documented in bacteria and were shown to participate in phage defense (Johnson et al, 2022; Koopal et al, 2022; Kuzmenko et al, 2020; Morehouse et al, 2020; Ofir et al, 2021). In the current study, we report on additional bacterial defense systems that encode domains known to be involved in animal immunity.…”

Section: Discussionmentioning

confidence: 99%

An expanding arsenal of immune systems that protect bacteria from phages

Millman

Melamed

Leavitt

et al. 2022

Preprint

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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.

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Section: Discussionmentioning

confidence: 99%

An expanding arsenal of immune systems that protect bacteria from phages

Millman

Melamed

Leavitt

et al. 2022

Preprint

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“…RM and CRISPR-Cas systems have previously been demonstrated to act additively against conjugal plasmid transfer in Enterococcus [32], and similarly in Streptococcus , RM and CRISPR-Cas systems can be compatible and increase overall phage resistance of the bacterial host [33]. Genomes that encode RM systems are actually shown to be more likely to encode CRISPR-Cas systems [31], and this genome co-occurrence is also observed with homologues of the Argonaute (ARGO)-PIWI family of proteins, which similarly function in the restriction of foreign DNA acquisition [34–36]. While co-occurrence could be indicative of co-transfer in ‘defence islands’, here they were shown to be rarely associated with proximity co-localization in the genome [31], further supportive of the provision of additive functionality [31, 32] and the conditions selecting for one also being positively selective for others.…”

Section: Repertoire Of Defence Mechanismsmentioning

confidence: 99%

Fitness costs of CRISPR-Cas systems in bacteria

Zaayman

Wheatley

2022

Microbiology

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CRISPR-Cas systems provide bacteria with both specificity and adaptability in defence against invading genetic elements. From a theoretical perspective, CRISPR-Cas systems confer many benefits. However, they are observed at an unexpectedly low prevalence across the bacterial domain. While these defence systems can be gained horizontally, fitness costs may lead to selection against their carriage. Understanding the source of CRISPR-related fitness costs will help us to understand the evolutionary dynamics of CRISPR-Cas systems and their role in shaping bacterial genome evolution. Here, we review our current understanding of the potential fitness costs associated with CRISPR-Cas systems. In addition to potentially restricting the acquisition of genetic material that could confer fitness benefits, we explore five alternative biological factors that from a theoretical perspective may influence the fitness costs associated with CRISPR-Cas system carriage: (1) the repertoire of defence mechanisms a bacterium has available to it, (2) the potential for a metabolic burden, (3) larger-scale population and environmental factors, (4) the phenomenon of self-targeting spacers, and (5) alternative non-defence roles for CRISPR-Cas.

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“…However, it remains unclear how bacterial TIR domaincontaining proteins enter the cell (Cirl et al, 2008;Rana et al, 2013;Spear et al, 2009). More recently, bacterial TIR domain-containing proteins have been implicated in antiphage defence systems (21)(22)(23)(24).…”

Section: Main Textmentioning

confidence: 99%

Chemical structures of cyclic ADP ribose (cADPR) isomers and the molecular basis of their production and signaling

Manik

Shi

et al. 2022

Preprint

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Cyclic ADP ribose (cADPR) isomers are important signaling molecules produced by bacterial and plant Toll/interleukin-1 receptor (TIR) domains via NAD+ hydrolysis, yet their chemical structures are unknown. We show that v-cADPR (2’cADPR) and v2-cADPR (3’cADPR) isomers are cyclized by O-glycosidic bond formation between the ribose moieties in ADPR. Structures of v-cADPR (2’cADPR)-producing TIR domains reveal that conformational changes are required for the formation of the active assembly that resembles those of Toll-like receptor adaptor TIR domains, and mutagenesis data demonstrate that a conserved tryptophan is essential for cyclization. We show that v2-cADPR (3’cADPR) is a potent activator of ThsA effector proteins from Thoeris anti-phage defence systems and is responsible for suppression of plant immunity by the effector HopAM1. Collectively, our results define new enzymatic activities of TIR domains, reveal the molecular basis of cADPR isomer production, and establish v2-cADPR (3’cADPR) as an antiviral signaling molecule and an effector-mediated signaling molecule for plant immunity suppression.One-Sentence SummaryThe chemical structures of two O-glycosidic bond-containing cyclic ADP ribose isomers, the molecular basis of their production, and their function in antiviral and plant immunity suppression by bacteria are reported.

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Short prokaryotic Argonaute systems trigger cell death upon detection of invading DNA

Cited by 134 publications

References 86 publications

An expanding arsenal of immune systems that protect bacteria from phages

An expanding arsenal of immune systems that protect bacteria from phages

Fitness costs of CRISPR-Cas systems in bacteria

Chemical structures of cyclic ADP ribose (cADPR) isomers and the molecular basis of their production and signaling

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