Prokaryotic innate immunity through pattern recognition of conserved viral proteins

Abstract

Many organisms have evolved specialized immune pattern-recognition receptors, including nucleotide-binding oligomerization domain–like receptors (NLRs) of the STAND superfamily that are ubiquitous in plants, animals, and fungi. Although the roles of NLRs in eukaryotic immunity are well established, it is unknown whether prokaryotes use similar defense mechanisms. Here, we show that antiviral STAND (Avs) homologs in bacteria and archaea detect hallmark viral proteins, triggering Avs tetramerization and the activation of diverse N-terminal effector domains, including DNA endonucleases, to abrogate infection. Cryo–electron microscopy reveals that Avs sensor domains recognize conserved folds, active-site residues, and enzyme ligands, allowing a single Avs receptor to detect a wide variety of viruses. These findings extend the paradigm of pattern recognition of pathogen-specific proteins across all three domains of life.

Accumulation of defense systems in phage resistant strains ofPseudomonas aeruginosa

“…The other 11 defense systems have morphotype-specific activities, targeting one (myophage-specific Druantia Type III and IetAS) or two phage morphotypes. This is in line with the sensing of specific conserved phage proteins, such as the capsid or terminase proteins, to trigger an immune response 26–28 .…”

“…Jumbo phages are known to produce a nuclear shell 34 that shields phage DNA during replication from DNA-targeting systems such as RM and CRISPR-Cas systems 35,36 . This suggests that CBASS Type III and AVAST Type V do not exert their anti-phage activity via direct DNA sensing or targeting, and instead may act on protein level (AVAST Type V) 26,29 or via induction of abortive infection upon sensing of a phage protein (CBASS Type III) 27 . Our results demonstrate that while Jumbo phages have developed specific mechanisms to counteract DNA-targeting defense systems, other defense systems have evolved a specificity that is effectively targeting Jumbo phages.…”

A family of novel immune systems targets early infection of nucleus-forming jumbo phages

“…For example, CRISPR-Cas and restrictionmodification systems typically target phage DNA rapidly in the cell prior to replication, whereas other, recently described anti-phage systems, such as DarTG 19 and Nhi 20 , appear to detect replicating DNA. In contrast, the recently described Avs (AntiVirus STAND) 21 , CapRel systems 22 , and likely CBASS 23 and Pycsar 24 , detect late expressed phage structural proteins. However, to our knowledge, no mechanism that detects ejected phage proteins has been reported.…”

“…Nevertheless, it seems clear that Juk represents a distinct modality of anti-phage defense whereby phage proteins ejected into the host cell are targeted before any phage specific process, such as expression of immediate early genes, takes place. Such mechanisms might be advantageous compared to those targeting late phage proteins in that they not only abrogate the phage reproduction but also allow the infected cell to survive, without the need to induce dormancy or programmed cell death as is the case with the Avs systems 21 and some CRISPR variants 28 . This work generates the potential that targeting ejected phage components, for example, the early transcription apparatus, is a common defense strategy, in which case many such systems, beyond Juk, remain to be identified.…”

Plant and prokaryotic TIR domains generate distinct cyclic ADPR NADase products

“…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). Further study of the TIR-domains encoded by prokaryotes and early plant lineages will shed light on the conservation of TIR-signals, and likely reveal new types of TIR-generated immune signals.…”