Molecular basis of CD-NTase nucleotide selection in CBASS anti-phage defense

Govande, A.A.; Duncan-Lowey, Brianna; Eaglesham, J.B.; Whiteley, Aaron T.; Kranzusch, Philip J.

doi:10.1016/j.celrep.2021.109206

Cited by 33 publications

(28 citation statements)

References 31 publications

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“…CBASS systems show diversity in both their activation mechanisms and their cell-killing mechanisms. All CBASS systems encode an oligonucleotide cyclase related to the mammalian innate-immune sensor cGAS (cyclic GMP-AMP synthase) that synthesizes a cyclic di- or trinucleotide second messenger molecule (8,9), and a second-messenger activated effector protein that mediates cell death to abort the viral infection. Type I CBASS systems encode only these two proteins, suggesting that their cGAS-like enzyme has an innate infection-sensing capability (10).…”

Section: Introductionmentioning

confidence: 99%

Control of bacterial immune signaling by a WYL domain transcription factor

Blankenchip

Nguyen

Lau

et al. 2022

Preprint

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Bacteria use diverse immune systems to defend themselves from ubiquitous viruses termed bacteriophages (phages). Many anti-phage systems function by abortive infection to kill a phage-infected cell, raising the question of how these systems are regulated to avoid activation and cell killing outside the context of infection. Here, we identify a transcription factor associated with the widespread CBASS bacterial immune system, that we term CapW. CapW forms a homodimer and binds a palindromic DNA sequence in the CBASS promoter region. Two crystal structures of CapW reveal how the protein switches from a DNA binding-competent state to a ligand-bound state that cannot bind DNA due to misalignment of dimer-related DNA binding domains. We show that CapW strongly represses CBASS gene expression in uninfected cells, and that CapW disruption likely results in toxicity due to uncontrolled CBASS expression. Our results parallel recent findings with BrxR, a transcription factor associated with the BREX anti-phage system, and suggest that CapW and BrxR are the founding members of a family of universal anti-phage signaling proteins.

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Section: Introductionmentioning

confidence: 99%

Control of bacterial immune signaling by a WYL domain transcription factor

Blankenchip

Nguyen

Lau

et al. 2022

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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“…However, because phages target important surface structures, such as the lipopolysaccharide (LPS) and membrane proteins as receptors, it is questionable whether mutations in receptors represent primary adaptive strategies in complex microbial communities because such modifications frequently incur fitness costs (6). Indeed, many additional defense mechanisms have recently been discovered, including CRISPR systems (14) and several other innate immunity mechanisms, many of which remain to be mechanistically characterized (15)(16)(17)(18)(19). Genes encoding both receptors and defense systems have been shown to occur frequently in variable genomic islands (6,(20)(21)(22) or to be associated with mobile genetic elements (23)(24)(25)(26).…”

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confidence: 99%

Rapid evolutionary turnover of mobile genetic elements drives bacterial resistance to phages

Hussain

Dubert

Elsherbini

et al. 2021

Science

116

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Although it is generally accepted that phages drive bacterial evolution, how these dynamics play out in the wild remains poorly understood. We found that susceptibility to viral killing in marine Vibrio is mediated by large and highly diverse mobile genetic elements. These phage defense elements display exceedingly fast evolutionary turnover, resulting in differential phage susceptibility among clonal bacterial strains while phage receptors remain invariant. Protection is cumulative, and a single bacterial genome can harbor 6 to 12 defense elements, accounting for more than 90% of the flexible genome among close relatives. The rapid turnover of these elements decouples phage resistance from other genomic features. Thus, resistance to phages in the wild follows evolutionary trajectories alternative to those predicted from laboratory-based evolutionary experiments.

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Molecular basis of CD-NTase nucleotide selection in CBASS anti-phage defense

Cited by 33 publications

References 31 publications

Control of bacterial immune signaling by a WYL domain transcription factor

Control of bacterial immune signaling by a WYL domain transcription factor

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

Rapid evolutionary turnover of mobile genetic elements drives bacterial resistance to phages

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