The conservation of immune systems from prokaryotes to eukaryotes can guide discovery of immunity genes across the tree of life. Most studies to date have focused on metazoan systems, while the extent...

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Recent discoveries on bacterial immunity have revealed that several protein domains involved in anti-phage defense are conserved in eukaryotes, such as SIRim, TIR, PNP and gasdermin. Bacterial immune ...

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CRISPR–Cas systems transcriptionally tune diverse innate defences using CRISPR RNA-like guides to balance antiviral protection with fitness, and hyperactivate these defences when compromised, establis...

Shomar, Guillaume, et al. report the genomics-driven discovery of a family of more than 2,000 lanthipeptide biosynthetic gene clusters with anti-phage potential. They experimentally demonstrate anti-p...

Gabija acts early during phage infection, preventing phage genome circularization and replication. Phage DNA end-binding proteins prevent RecBCD loading onto linear DNA, and the absence of RecBCD lice...

Defense-associated reverse transcriptases (DRTs) employ DNA synthesis to protect bacteria against phage infection. We previously showed that DRT10, a tripartite system comprising an RT, a noncoding RNA (ncRNA), and a SLATT effector protein, catalyzes protein-primed, tandem-repeat DNA synthesis in a mechanism strikingly analogous to eukaryotic telomerase. However, the structural basis by which the RT-ncRNA complex directs repeat addition processivity and controls repeat length remains unknown. Here we present cryo-EM reconstructions of two evolutionarily diverse DRT10 RT-ncRNA systems that reveal an unanticipated 2:1 architecture, wherein two RT monomers bind opposite sides of a single, pseudo-symmetric ncRNA. Biochemical experiments demonstrate that each RT monomer reverse transcribes the template encoded on its respective side of the ncRNA, but only one generates the long repetitive product, with the template sequence defined by the distance between two flanking stem-loop anchors. Together with earlier studies of DRT2, DRT3, and DRT9, our findings identify a conserved mechanistic logic underlying ncRNA-templated tandem-repeat synthesis across Class 2 UG antiviral systems, despite vastly different architectural solutions. ### Competing Interest Statement Columbia University has filed a patent application related to this work. S.H.S. is a co-founder and scientific advisor to Dahlia Biosciences, a scientific advisor to CrisprBits and Prime Medicine, and an equity holder in Dahlia Biosciences and CrisprBits. The remaining authors declare no competing interests.

Nature Structural & Molecular Biology, Published online: 24 June 2026; doi:10.1038/s41594-026-01840-5Human Argonaute 2 requires distortion of the paired small interfering RNA (siRNA)–target RNA duplex, not just base pairing, to cleave targets. Structures show how RNA shape and key residues enable catalysis, explaining why some siRNAs are more effective.

Structures of the AGO maturation complex reveal how chaperones and an RNA duplex drive assembly of the RNA-induced silencing complex.

Nature Microbiology, Published online: 27 May 2026; doi:10.1038/s41564-026-02355-xThe prophage of a clinical Enterobacter isolate uses an RNA-guided transcription factor to alter flagellar composition, leading to enhanced bacterial motility and improved gut colonization in a mouse model.

A better understanding of battles between bacteria and viruses could inspire new medicines

Tak et al. discover that bacteria use 2′,3′-cGAMP, the same signaling molecule employed by mammalian cGAS-STING, for phage defense. In response to phage, 2′,3′-cGAMP activates filament formation of Ca...

Nature Structural & Molecular Biology, Published online: 18 March 2026; doi:10.1038/s41594-026-01753-3Zheng et al. show that extending the guide RNA restores the reduced activity of a high-fidelity CRISPR–Cas9 enzyme while preserving accuracy, revealing how strengthened PAM-distal interactions can improve genome-editing performance.

Nature Microbiology, Published online: 10 March 2026; doi:10.1038/s41564-026-02288-5RNA-targeting CRISPR in Listeria seeligeri restricts the lytic cycle of temperate phages but tolerates prophage acquisition while also preventing induction—a system that enables acquisition of beneficial prophages while mitigating the risks of lysis.

Anti-CRISPRs (Acrs) are diverse proteins or RNAs that protect invading phages and plasmids from host CRISPR-Cas immunity. Most Acrs neutralize their cognate Cas proteins via direct physical interaction. Here we describe CasPRs, a particularly widespread family of DNA-binding Acrs that recognize specific sequence motifs within cas gene coding regions, thereby blocking RNA polymerase and silencing transcription. We demonstrate that eight diverse CasPRs bind to the cas8b gene to repress the type I-B CRISPR-Cas system in its native host, Listeria seeligeri . Meanwhile, a CasPR from Streptococcus dysgalactiae silences type II-A CRISPR-Cas immunity by binding to the cas9 coding sequence. We found that one CasPR is required to inhibit CRISPR immunity during lysogeny by its host prophage. Taken together, our results indicate that members of the CasPR family have diverged to silence completely unrelated CRISPR types, and suggest transcriptional repression is a common mode of phage-mediated immune antagonism. ### Competing Interest Statement AJM is a co-founder and advisor of Profluent Bio. The other author declares no competing interests. National Institute of General Medical Sciences, https://ror.org/04q48ey07, R35GM142460, GM136534 U.S. National Science Foundation, FAIN2235762 Defense Advanced Research Projects Agency, https://ror.org/02caytj08, HR00112590142 Rita Allen Foundation, https://ror.org/0515k5w36

This study shows how the bacterial retron Eco2 defends against viruses. Phage nucleases trigger activation of Eco2, which cuts RNAs, shuts down protein production and stops phage replication.

Most mitochondrial proteins are produced in the cytosol and imported through the translocase of the outer mitochondrial membrane (TOM) to reach their final destination. Although this protein entry gat...

From populations of multicellular organisms to selfish genetic elements, conflicts between levels of biological organization are central to evolution. Plasmids are extrachromosomal, self-replicating g...

Antiviral immune systems diversify by integrating new genes into existing pathways, creating new mechanisms of viral resistance. We identified genes encoding a predicted nuclease paired with a trypsin...

An exploration of previously undescribed variants from the long tail of the CRISPR–Cas distribution.