Senior Research Associate, microbiologist, biochemist, The Sorek lab, Weizmann Institute of Science
Osterman Ilya
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Another cool phage enzyme discovery! It degrades Thoeris signaling molecules into ADPR. Congrats to Miguel and all involved 🧬
Happy to see the paper out in Cell Host & Microbe. congratulations Ilya!
Our paper is out in Nature Microbiology: functional analysis of 80 phage sponges, revealing new sponges that inhibit bac immunity by binding the immune signals cCMP, cUMP and N7-cADPR
Thanks to all coauthors and our collaborators at the Kranzusch Lab. Congrats Romi!
www.nature.com/articles/s41...
Our aRES story is finally out 😀
Beyond what was reported in the preprint, we found that aRES is activated by direct binding of the phage DNA polymerase.
Another NAD-degrading defense system — and multiple phage strategies to overcome it.
www.sciencedirect.com/science/arti...
Phage receptor-binding proteins are known for their LEGO-like modularity, but we still do not fully understand their evolutionary potential and how it shapes phage host range. Our new preprint examines this systematically in Klebsiella phages. 🔗 www.biorxiv.org/content/10.6...
Thread 🧵
Bacteria vs phage: new layers in NAD+ centric arms race
aRES is bacterial protein that blocks phage infection by cleaving NAD+ into ADPR-1P & nicotinamide. Phages counter using NAD+ reconstitution pathway w/ADPR-1P & nicotinamide as substrates
www.cell.com/cell-host-mi...
www.nature.com/articles/s41...
Phage T4 boosts defense with 2 glucosyltransferases adding glucose to 5-hmC on DNA to ev… PMID:42206360, Nucleic Acids Res 2026, @NAR_Open @OTSociety @NAR_Open https://doi.org/10.1093/nar/gkag531 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪
Excited to see our work out in @natmicrobiol.nature.com! We uncovered broad functional diversity within phage sponge families🧽.
Huge thanks to all coauthors and brilliant collaborators @kranzuschlab.bsky.social @reneechang.bsky.social !
www.nature.com/articles/s41...
Osterman et al. describe a bacterial defense protein that, once triggered by the phage
DNA polymerase, blocks infection by cleaving NAD+ into ADPR-1P and nicotinamide. They
show how phages counter thi...
Many bacterial defense systems restrict phage infection by breaking down the molecule nicotinamide (Nam) adenine dinucleotide (NAD+) into adenosine di…
Our aRES story is finally out 😀
Beyond what was reported in the preprint, we found that aRES is activated by direct binding of the phage DNA polymerase.
Another NAD-degrading defense system — and multiple phage strategies to overcome it.
www.sciencedirect.com/science/arti...
Rafal Mostowy
Improved fractionation strategies can identify antibiotics with previously unseen scaffolds and mechanisms, exemplified by manikomycin from Streptomyces rimosus, which acts by targeting the E-site of ...
Excited to see our work out in @natmicrobiol.nature.com! We uncovered broad functional diversity within phage sponge families🧽.
Huge thanks to all coauthors and brilliant collaborators @kranzuschlab.bsky.social @reneechang.bsky.social !
www.nature.com/articles/s41...
(1/6) Thrilled to share this story! In our preprint from my PhD in the @kranzuschlab.bsky.social, with help from the Hatfull lab and @soreklab.bsky.social, we discover RyDEP, a phage-encoded RyR-domain glycosidase that allows phages to evade Thoeris defense. Highlights below! doi.org/10.64898/202...
A functional screen reveals phage sponge proteins that bind Pycsar, Thoeris and CBASS signalling molecules to inhibit bacterial immunity.
🧬 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...
Romi Hadary
Wilson Lab
Osterman Ilya
Many bacterial defense systems restrict phage infection by breaking down the molecule nicotinamide (Nam) adenine dinucleotide (NAD+) into adenosine di…
📢 Preprint out!
Together with @reneechang.bsky.social @kranzuschlab.bsky.social and the amazing @soreklab.bsky.social, we explored viral sponges to map their diversity and function.
Discovered huge diversity, including sponges that inhibit Pycsar & Type IV Thoeris!
www.biorxiv.org/content/10.1...
Romi Hadary
A functional screen reveals phage sponge proteins that bind Pycsar, Thoeris and CBASS signalling molecules to inhibit bacterial immunity.
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
🧬 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...
📢 Preprint out!
Together with @reneechang.bsky.social @kranzuschlab.bsky.social and the amazing @soreklab.bsky.social, we explored viral sponges to map their diversity and function.
Discovered huge diversity, including sponges that inhibit Pycsar & Type IV Thoeris!
www.biorxiv.org/content/10.1...
Multiple bacterial immune systems, including CBASS, Thoeris, and Pycsar, employ signaling molecules that activate the immune response following phage infection. Phages counteract bacterial immune sign...
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
Multiple bacterial immune systems, including CBASS, Thoeris, and Pycsar, employ signaling molecules that activate the immune response following phage infection. Phages counteract bacterial immune sign...
