Kranzusch Lab

Synteny-aware functional annotation of bacteriophage genomes with Phynteny Accurate genome annotation is fundamental to decoding viral diversity and understanding bacteriophage biology; yet, the majority of bacteriophage genes remain functionally uncharacterised. Bacteriopha...

🚨 New preprint 🚨

My phage annotation tool, Phynteny, finally has a preprint and a brand new version powered by a cool AI transformer architecture and protein language models! #phagesky

www.biorxiv.org/content/10.1...

Manipulation of the nucleotide pool in human, bacterial and plant immunity - Nature Reviews Immunology Modification of the nucleotide pool is emerging as key to innate immunity in animals, plants and bacteria. This Review explains how immune pathways conserved from bacteria to humans manipulate the nuc...

We wrote a review on the free nucleotide pool as a central playground in human, bacterial, and plant immunity – now out in Nature Reviews in Immunology

www.nature.com/articles/s41...

Was fun to write this piece with Dina Hochhauser!

Here is a thread to explain the premises

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Manipulation of the nucleotide pool in human, bacterial and plant immunity - Nature Reviews Immunology Modification of the nucleotide pool is emerging as key to innate immunity in animals, plants and bacteria. This Review explains how immune pathways conserved from bacteria to humans manipulate the nuc...

NEW Review from @soreklab.bsky.social @dinahoch.bsky.social explains how immune pathways manipulate the availability of nucleotides, chemically modify nucleotides to generate immune signalling molecules, and produce altered nucleotides that poison viral replication
#immunosky #microsky #phagesky

Very proud to have our lab’s first work published in @cp-cellhostmicrobe.bsky.social!

In this work, we use functional metagenomics to find phage defenses from human and soil microbiomes!

Congrats to first author @luis840alberto.bsky.social !

www.cell.com/cell-host-mi...

(1/3)

Recurrent acquisition of nuclease-protease pairs in antiviral immunity https://www.biorxiv.org/content/10.1101/2025.07.28.667249v1

Kiwa is a membrane-embedded defense supercomplex activated at phage attachment sites Zhang, Todeschini, and Wu et al. show that the bacterial defense system Kiwa senses phage attachment at the membrane and assembles a transmembrane complex that halts infection by blocking phage DNA re...

Thrilled to see our Kiwa story out today! A membrane-associated supercomplex that senses infection and blocks replication and transcription.

www.cell.com/cell/fulltex...

Huge congratulations to Yi and Zhiying for bringing it home, to Thomas for starting us off, and to all the collaborators.

Bacterial Schlafens mediate anti-phage defense Human Schlafen proteins restrict viral replication by cleaving tRNA, thereby suppressing protein synthesis. Although the ribonuclease domain of Schlafen proteins is conserved across all domains of lif...

First preprint from the Nemudryi Lab! 🍾

In this work, we link antiviral immunity in bacteria and humans by showing that homologs of human Schlafen nucleases protect bacteria from phages.

www.biorxiv.org/content/10.1...

A human homolog of SIR2 antiphage proteins mediates immunity via the Toll-like receptor pathway Key actors of mammalian immunity originated from bacterial antiphage systems. The full extent of immune system conservation between bacteria and eukaryotes is unknown. Here, we show that the silent in...

Many components of human immunity evolved from ancient pathways in bacteria. A beautiful story from @audeber.bsky.social‬ @enzopoirier.bsky.social‬ leverages this evolutionary connection to discover SIRal as a signaling protein in animal TLR-mediated innate immunity.

www.science.org/doi/10.1126/...

Exciting study with both phage gene essentiality maps and mutant analysis for many recently described phage defense systems. Especially interesting results for phage proteins that induce RADAR dATP>dITP conversion!

Astounding new structure of a nucleotide immune signal degrading enzyme. The field has found enzymes with this function that look like nucleases, enzymes that look like nucleotide binding proteins, even enzymes that look like proteases... but never a fold like this!

www.biorxiv.org/content/10.1...

A miniature CRISPR-Cas10 enzyme confers immunity by an inverse signaling pathway Microbial and viral co-evolution has created immunity mechanisms involving oligonucleotide signaling that share mechanistic features with human anti-viral systems[1][1]. In these pathways, including C...

Clover joins a surprising set of systems using inhibitory nucleotide signals. See MISS/Panoptes @benadler.bsky.social @erinedoherty.bsky.social‬ @aesully98.bsky.social‬ and Hailong @joelmjtan.bsky.social‬

www.nature.com/articles/s41...
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...

Named after the four-leaf clover architecture of CloA revealed by Sonomi’s cryo-EM structures, Clover senses dTTP to detect viral enzymes that increase nucleotide abundance and is also self-inhibited by the nucleotide signal p3diT that restrains activation to prevent immune-associated toxicity.

A new preprint led by Sonomi Yamaguchi in our lab describes a bacterial anti-phage defense system named Clover that uses nucleotide signals to both activate and inhibit host immunity.

www.biorxiv.org/content/10.1...

SAM-AMP lyases in type III CRISPR defence Abstract. Type III CRISPR systems detect non-self RNA and activate the enzymatic Cas10 subunit, which generates nucleotide second messengers for activation

Beautiful new story on Type III CRISPR from the White and Gloster Labs. SAM-AMP continues to be an incredibly surprising nucleotide signal in phage defense!
academic.oup.com/nar/article/...

📢Preprint out!
Excited to share my final work from the @soreklab.bsky.social!

We mined phage dark matter using structural features shared by anti-defense proteins (viral tools that help phages bypass bacterial immunity) to guide discovery.

Found 3 new families targeting immune signaling!

Preprint: “Structural modeling reveals viral proteins that manipulate host immune signaling”

Using AI-guided structural modeling, we find new families of viral proteins that sequester or cleave host immune signaling molecules

Congrats Nitzan Tal!

www.biorxiv.org/content/10.1...

Some nuclease-NTPase systems cleave all DNA targets and others are more specific. Each system requires all complex subunits for target cleavage. Check out Figure 5 for a summary of our data and results in the field that we hope will serve as a guide for others studying these types of systems. (7/7)

In every system we tested, nuclease and NTPase subunits combine to form large protein complexes. We used mass photometry to create experimentally guided structural models and deep sequencing to define cleavage site specificities. (6/7)

Our large-scale comparative analysis defines shared molecular features of 16 nuclease-NTPase defense systems. Using the @aharms485.bsky.social‬ BASEL phage collection, we show that these systems can exhibit broad anti-phage defense or specific targeting of individual phage families. (5/7)

Nuclease-NTPase systems comprise >10% of recently identified anti-phage defense operons, including AbpAB, Azaca, PD-T4-4, Mokosh, and Menshen. Are other nuclease-NTPase systems similar to Gabija or Hachiman? Can we define the general principles controlling this type of antiviral defense? (4/7)

Structures of Gabija from our group and the Zhu, Wang, Fu, and Wei labs explained how nuclease and NTPase subunits assemble into a supramolecular complex to control phage defense, while @doudna-lab.bsky.social structures of Hachiman revealed a 1:1 assembly with distinct DNA cleavage activity. (3/7)

Previously, @soreklab.bsky.social discovered diverse defense operons in bacteria including systems they named Gabija and Hachiman – both two gene operons that each encode a nuclease and a partnering NTPase-superfamily protein. (2/7)

Nuclease-NTPase systems use shared molecular features to control bacterial anti-phage defense Bacteria encode an enormous diversity of defense systems including restriction-modification and CRISPR-Cas that cleave nucleic acid to protect against phage infection. Bioinformatic analyses demonstra...

Starting the lab Bluesky account to share a preprint from @aragucci.bsky.social and @sadieantine.bsky.social‬ that reveals molecular principles shared across diverse nuclease-NTPase anti-phage defense systems in bacterial immunity (1/7)

www.biorxiv.org/content/10.1...