Bacterial defense via RES-mediated NAD+ depletion is countered by phage phosphatases
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-1β³-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
𧬠Metabolic arms race continues!
We discovered a new NADβΊ-depleting bacterial immune system aRES and phage enzymes that overcome it.
Our preprint is out: www.biorxiv.org/content/10.6...
29.01.2026 11:20 β π 26 π 15 π¬ 1 π 5
Great new story from Sophie Helaine and Molly Sargen!
www.helainelab.com
28.01.2026 23:01 β π 34 π 18 π¬ 0 π 0
Phold's manuscript is now available @narjournal.bsky.social thanks to @susiegriggo.bsky.social @npbhavya.bsky.social @vijinim.bsky.social @linsalrob.bsky.social @martinsteinegger.bsky.social @milot.bsky.social @eunbelivable.bsky.social & others not on bsky #phagesky academic.oup.com/nar/article/...
14.01.2026 05:10 β π 82 π 44 π¬ 1 π 1
Phage-associated Cas12p nucleases require binding to bacterial thioredoxin for activation and cleavage of target DNA www.nature.com/articles/s41...
04.01.2026 05:56 β π 18 π 8 π¬ 0 π 0
#microsky #phagesky
03.01.2026 12:07 β π 9 π 1 π¬ 0 π 0
@peterfineran.bsky.social and colleagues develop Tn-seq for phages by leveraging anti-CRISPR (Acr) as a positive
selectable marker in the presence of CRISPR-Cas counter-selection, and identify essential genes in phage from non model orgs
www.biorxiv.org/content/10.6...
20.12.2025 23:34 β π 52 π 24 π¬ 1 π 1
β¨New preprint!
π§΅1/4 Excited to share our work on AI-guided design of minimal RNA-guided nucleases. Amazing work by @petrskopintsev.bsky.social @isabelesain.bsky.social @evandeturk.bsky.social et al!
Multi-lab collaboration @banfieldlab.bsky.social @jhdcate.bsky.social @jacobsenucla.bsky.socialπ§¬
ππ
09.12.2025 07:52 β π 98 π 47 π¬ 1 π 8
Phages are full of genes of unknown function that are likely adaptive in specific conditions.
New preprint: Phage TnSeq identifies essential genes rapidly and knocks all non-essentials. We would like to send a pool of phiKZ mutants to anyone wanting it! Reach out
tinyurl.com/bdcfrejh
08.12.2025 15:04 β π 90 π 42 π¬ 2 π 2
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
04.12.2025 13:56 β π 34 π 13 π¬ 1 π 0
π§¬π‘οΈHow are new immune mechanisms created?
We show how Lamassu antiphage system, originated from a DNA-repair complex and evolved into a compact and modular immune machine, wt Dinshaw Patel lab in @pnas.org.
π @matthieu-haudiquet.bsky.social, Arpita Chakravarti & all authors!
doi.org/10.1073/pnas...
27.11.2025 09:35 β π 104 π 47 π¬ 1 π 2
Divergent viral phosphodiesterases for immune signaling evasion
Cyclic dinucleotides (CDNs) and other short oligonucleotides play fundamental roles in immune system activation in organisms ranging from bacteria to β¦
Work I co-led with @jnoms.bsky.social is now online at
@cp-cellhostmicrobe.bsky.social ! We revealed a previously unrealized diversity of viral immune-evasion proteins that selectively destroy different cyclic nucleotide signals used in bacterial immunity.
www.sciencedirect.com/science/arti...
25.11.2025 21:10 β π 51 π 21 π¬ 1 π 3
New from the @doudna-lab.bsky.social and first author @owentuck.bsky.social!
14.11.2025 00:27 β π 7 π 3 π¬ 0 π 0
Bacteria can sense when a virus starts shredding their genome β by detecting methylated mononucleotides.
Hereβs the story of how we discovered the Metis defense system π
www.biorxiv.org/content/10.1...
06.11.2025 04:59 β π 132 π 49 π¬ 4 π 12
Antiviral reverse transcriptases reveal the evolutionary origin of telomerase
Defense-associated reverse transcriptases (DRTs) employ diverse and distinctive mechanisms of cDNA synthesis to protect bacteria against viral infection. However, much of DRT family diversity remains ...
1/10 Genome maintenance by telomerase is a fundamental process in nearly all eukaryotes. But where does it come from?
Today, we report the discovery of telomerase homologs in a family of antiviral RTs, revealing an unexpected evolutionary origin in bacteria.
www.biorxiv.org/content/10.1...
17.10.2025 17:22 β π 222 π 106 π¬ 5 π 16
Asst. Prof. at Copenhagen University. Excited about phages, plasmids, and bacterial immunity!π¨βπ¬π¬ https://pinillaredondolab.com/
Doudna Lab at UC Berkeley, Innovative Genomics Institute founder, CRISPR co-inventor and Nobel laureate innovativegenomics.org/
DFG funded Priority Programme SPP2330 focusing on prokaryotic virus-host interactions. Account managed by Dr. Eva Davoudi
Homepage https://spp2330.de/
Principal Investigator at @aithyra.bsky.social | Structural bioinformatics, virology, and innate immunity | jasonnomburg.com
Postdoc studying evolutionary microbiology with phage and pseudomonas at MMSB Lyon, France with Anne Chevallereau in the MEEP group (She/Her)
Assistant Professor, NISER, India.
Bacterial and phage genetics.
Bacterial immune systems and phage encoded anti-microbials.
Curious how immune systems differentiate partner from pathogen:
bacteria-phage | macrophage-cancer | orchid-fungi
Genetics PhD candidate @stanford
Formerly orchid ecologist @smithsonian
chem bio PhD student in the Doudna Lab @Berkeley
Harvard Medical School, Dana Farber Cancer Institute
https://kranzuschlab.med.harvard.edu
PhD student @soreklab.bsky.social. Researching the arms race between bacteria and phages π¦ π‘βοΈ A proud father of 3 cats. π³οΈβπ
PhD student @Soreklab.bsky.social @WeizmannScience
Studying phage-bacteria arms raceπ¦ π‘οΈ
Research Fellow at Northumbria University: phage, synthetic biology, sialic acid, transport proteins. He/him.
scientist. shipman lab at gladstone | UCSF.
RNA, microbiology, infectious disease; Helmholtz Institute for RNA-based Infection Research & University of WΓΌrzburg, Germany
www.helmholtz-hiri.de
SomeoneββPostdocβMGEsβHGTβPhage person but sometimes anti-phage
Bioinformatics Scientist / Next Generation Sequencing, Single Cell and Spatial Biology, Next Generation Proteomics, Liquid Biopsy, SynBio, AI/ML in biotech // http://albertvilella.substack.com
Bacterial plasticity, integrons, phage defence
DR2-CNRS, cheffe de groupe @Institut Pasteur
Dad of two, Professor, Lister Research Fellow and Wellcome Investigator at the John Innes Centre. Interested in bacterial chromosome organization & segregation, plasmids, and phages.
www.tunglelab.org
