New Thoeris systems and new bacterial TIRs, this time also producing plant and human immune signals 2'cADPR and cADPR!!! Congratulations to @erezyirmiya.bsky.social and Azita Leavitt! It was a pleasure to be involved in this project.
A massive expansion of Thoeris defense systems !
Congrats @erezyirmiya.bsky.social and @soreklab.bsky.social
TIR domains across diverse eukaryotes are enzymatically active. Especially interesting is the human TLR4 TIR, long thought to be enzymatically inactive, now shown to be catalytically active and to produce cADPR, a molecule involved in immunity across domains of life. Congrats, Bohdana!!
New Thoeris systems reveal a deep connection between bacterial TIR-produced immune signals to plant and human immunity🦠🌱🧍♀️
It was a great honor to contribute to this project! Congratulations to @erezyirmiya.bsky.social and Azita Leavitt!!🎉🥂
Thoeris - the gift that keeps on giving 🦠🎁! Congrats Erez, Azita et al.!
Incredible to learn how far-reaching and diverse Thoeris really is! TIRs play key roles across kingdoms, and this work beautifully highlights their bacterial origins.
Congrats @erezyirmiya.bsky.social & Azita! 👏🌟
Honored to be part of the 2026 cohort and looking forward to the journey ahead! @schmidtfellows.bsky.social
The plot thickens! Exciting new discoveries in the NAD⁺ centric battlefield between bacteria and phages. Congrats, Ilya!
Preprint: Systematic discovery of TIR-based immune signaling systems in bacteria
Conservation of TIR-derived signals accross the tree of life! We found bacterial TIR immune systems that signal via canonical cADPR (like in humans) and 2'cADPR (a plant immune signal).
Documented 11 Thoeris types
Osterman Ilya
François Rousset
Erez Yirmiya
Erez Yirmiya
Erez Yirmiya
Bohdana Hurieva🇺🇦
Romi Hadary
Gal Ofir
I’m happy to share our new preprint! We uncovered the full diversity of bacterial TIR-based antiviral immune signaling, massively expanded the known diversity of Thoeris systems, and revealed conservation of TIR-derived immune signals across the tree of life.
www.biorxiv.org/content/10.6...
Sorek Lab
I’m happy to share our new preprint! We uncovered the full diversity of bacterial TIR-based antiviral immune signaling, massively expanded the known diversity of Thoeris systems, and revealed conservation of TIR-derived immune signals across the tree of life.
www.biorxiv.org/content/10.6...
I’m happy to share our new preprint! We uncovered the full diversity of bacterial TIR-based antiviral immune signaling, massively expanded the known diversity of Thoeris systems, and revealed conservation of TIR-derived immune signals across the tree of life.
www.biorxiv.org/content/10.6...
🎉Excited to share our new preprint!
TIR domains from diverse animals, including human TLR4, are catalytically active and produce cyclic ADP-ribose (cADPR). This enzymatic activity is widespread in animals and conserved across the tree of life.
www.biorxiv.org/content/10.6...
I’m happy to share our new preprint! We uncovered the full diversity of bacterial TIR-based antiviral immune signaling, massively expanded the known diversity of Thoeris systems, and revealed conservation of TIR-derived immune signals across the tree of life.
www.biorxiv.org/content/10.6...
I’m happy to share our new preprint! We uncovered the full diversity of bacterial TIR-based antiviral immune signaling, massively expanded the known diversity of Thoeris systems, and revealed conservation of TIR-derived immune signals across the tree of life.
www.biorxiv.org/content/10.6...
Erez Yirmiya
🧬 Metabolic arms race continues!
We discovered a new NAD⁺-depleting bacterial immune system aRES and phage enzymes that overcome it.
Our preprint is out: www.biorxiv.org/content/10.6...
www.biorxiv.org
Erez Yirmiya
Erez Yirmiya
We are thrilled to introduce our 2026 Schmidt Science Fellows — thirty-two incredible scientists set to embark on the next step of their interdisciplinary journey with our support. schmidtsciencefellows.org/news/the-202... @schmidtsciences.bsky.social
Bohdana Hurieva🇺🇦
Erez Yirmiya
I’m happy to share our new preprint! We uncovered the full diversity of bacterial TIR-based antiviral immune signaling, massively expanded the known diversity of Thoeris systems, and revealed conservation of TIR-derived immune signals across the tree of life.
www.biorxiv.org/content/10.6...
Many bacterial defense systems restrict phage infection by breaking the molecule NAD+ to its constituents, adenosine diphosphate ribose (ADPR) and nicotinamide (Nam). To counter NAD+ depletion-mediated defense, phages evolved NAD+ reconstitution pathway 1 (NARP1), which uses ADPR and Nam to rebuild NAD+. Here we report a bacterial defense system called aRES, involving RES-domain proteins that degrade NAD+ into Nam and ADPR-1″-phosphate (ADPR-1P). This molecule cannot serve as a substrate for NARP1, so that NAD+ depletion by aRES defends against phages even if they encode NARP1. We further discover that some phages evolved an extended NARP1 pathway capable of overcoming aRES defense. In these phages, the NARP1 operon also includes a specialized phosphatase, which dephosphorylates ADPR-1P to form ADPR, a substrate from which NARP1 then reconstitutes NAD+. Other phages encode inhibitors that directly bind aRES proteins and physically block their active sites. Our study describes new layers in the NAD+-centric arms race between bacteria and phages and highlights the centrality of the NAD+ pool in cellular battles between viruses and their hosts. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, ERC-AdG GA 101018520 Israel Science Foundation, MAPATS grant 2720/22 Deutsche Forschungsgemeinschaft, SPP 2330, grant 464312965 Minerva Foundation with funding from the Federal German Ministry for Education and Research research grant from Magnus Konow in honor of his mother Olga Konow Rappaport Ministry of Aliyah and Immigrant Absorption, https://ror.org/05aycsg86 Clore Scholars Program
Toll/interleukin-1 receptor (TIR) domains are important for immune signaling across humans, plants and bacteria. These domains were recently found to produce immune signaling molecules in plant immuni...
Toll/interleukin-1 receptor (TIR) domains are important for immune signaling across humans, plants and bacteria. These domains were recently found to produce immune signaling molecules in plant immuni...
www.biorxiv.org
Toll/interleukin-1 receptor (TIR) domains are important for immune signaling across humans, plants and bacteria. These domains were recently found to produce immune signaling molecules in plant immuni...
Toll/interleukin-1 receptor (TIR) domains are important for immune signaling across humans, plants and bacteria. These domains were recently found to produce immune signaling molecules in plant immuni...
www.biorxiv.org
Toll/interleukin-1 receptor (TIR) domains are important for immune signaling across humans, plants and bacteria. These domains were recently found to produce immune signaling molecules in plant immuni...
Toll/interleukin-1 receptor (TIR) domains are important for immune signaling across humans, plants and bacteria. These domains were recently found to produce immune signaling molecules in plant immuni...
