With Eugene Koonin, we propose a concept of βthe selfish ribosomeβ, under which evolution of life is viewed as a ribosomal takeover, where the ribosome evolved to consume most of the cellβs resources, while other cellular componentry ensures the propagation of the ribosome. arxiv.org/abs/2602.23268
03.03.2026 08:58 β
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Elegant study from @erinhuiting.bsky.social @jbdsf.bsky.social on CBASS phage inhibition without loss of cell viability. Especially interesting to see this phenotype with a CapV membrane-targeting effector and evidence for 3'3'-cGAMP transport!
www.biorxiv.org/content/10.6...
26.02.2026 12:20 β
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Happy by a recent biorxiv pre-print about DARNA (PD-T7-3) anti-phage defense system. This system is activated by binding to ssDNA, presented by phage SSB, to cleave tRNA in the anti-codon loop.
www.biorxiv.org/content/10.6...
24.02.2026 08:08 β
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New preprint on Detectrons from @jihoon-han.bsky.social! These are programmable biosensors for RNA that produce DNA barcodes in the presence of their target RNA. Check out Jihoon's quoted thread and the preprint for more:
www.biorxiv.org/content/10.6...
18.02.2026 18:24 β
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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
We found a new mode by which bacteria deplete NAD+ to protect from phages. And then we found how phages overcome this defense
Discovered by talented biochemist Dr Ilya Osterman, read the preprint: tinyurl.com/Narp-ap
A thread π§΅
29.01.2026 15:34 β
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A methylome-derived m6-dAMP trigger assembles a PUA-Cal-HAD immune filament that depletes dNTPs to abort phage infection
Bacteria must distinguish phage attack from normal homeostatic processes, yet the danger signals that trigger many defence systems remain unknown. Here, we show that a PUA-Calcineurin-CE-HAD module from Escherichia coli ECOR28 confers broad anti-phage protection by binding Dam-methylated deoxyadenosine monophosphate (m6-dAMP) generated during phage-induced chromosome degradation. Ligand binding converts a preassembled PUA-Calcineurin-CE hexamer loaded with six HAD phosphatases into a polymerising filament. The filament acts as a high-flux dNTP sink through a two-enzyme cascade: HAD first dephosphorylates dATP to dADP, and Calcineurin-CE then converts dADP to dAMP. dNTP collapse halts phage replication and enforces abortive infection. Multiple mobile-element DNA mimic proteins block filament assembly, revealing a direct phage counter-defence. More broadly, our findings extend a conserved, cross-kingdom paradigm of immune filament assembly to nucleotide-depletion antiviral defence and suggest modified-nucleotide sensing by related PUA-Calcineurin-CE modules as a widespread, underappreciated bacterial strategy. ### Competing Interest Statement The authors have declared no competing interest. NIHR Southampton Biomedical Research Centre, https://ror.org/01qqpzg67, Postdoctoral Bridging Fellowship F.L.N. is supported by a Wessex Health Partners (WHP) and National Institute for Health and Care Research Wessex Experimental Medicine Network (NIHR WEMN), Seed fund National Institutes of Health, GM145888, U24 GM129539) Maloris Foundation Memorial Sloan Kettering Cancer Center, P30-CA008748 Simons Foundation, SF349247 New York State Assembly
Preprint out: We characterise PUA-Cal-HAD, a widespread bacterial antiphage defence family. An infection cue switches a preassembled complex into an immune filament that drains dNTPs via a coupled two-enzyme cascade, and phage DNA mimics can block filament assembly (anti-polymerisation).
17.01.2026 14:52 β
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Most plasmids described in E. coli are small compared to the megaplasmids we identified here! Check out the preprint if you want to learn about these mysterious large elements and their potential functions π§¬. Iβm very grateful to have had the opportunity to work on this in @banfieldlab.bsky.social
01.10.2025 05:10 β
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RNA-triggered Cas12a3 cleaves tRNA tails to execute bacterial immunity - Nature
Cas12a3 nucleases constitute a distinct clade of type V CRISPRβCas bacterial immune systems that preferentially cleave the 3β² tails of tRNAs after recognition of target RNA to induce growth arres...
Our paper is out! Hiding in plain sight among Cas12a nucleases, Cas12a3 cleaves not its RNA target but the 3β² ends of tRNA. Huge thanks to all who made this possible, especially the Beisel lab, Biao & Dirk for the structure, & @sebastianglatt.bsky.social for all things tRNA. doi.org/10.1038/s415...
07.01.2026 16:15 β
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The EMBO Gold Medal 2025 was awarded to Tanmay Bharat and David Bikard: https://www.embo.org/press-releases/embo-gold-medal-2025-awarded-to-tanmay-bharat-and-david-bikard/ π§ͺ
At #CellBio2025, the EMBO Gold Medal was handed over to David Bikard in recognition of his pioneering work on #GeneEditing.
10.12.2025 13:40 β
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Structural basis of Retron-Eco8-mediated anti-phage defense https://www.biorxiv.org/content/10.64898/2025.12.04.692459v1
06.12.2025 02:47 β
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β NAR Breakthrough! β
π¦ New study shows phage X1 hijacks Yersinia's enterocolitica flagellum to inject its DNA directly into the cytosol. Yersinia, though, strikes back!
π¦ A fascinating look at the #dualrole of #flagella in #viralentry and #bacterialimmunity.
𧬠Read more: doi.org/10.1093/nar/...
25.11.2025 17:09 β
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Bacteriophage genome-wide transposon mutagenesis https://www.biorxiv.org/content/10.1101/2025.11.23.690004v1
25.11.2025 03:17 β
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π¨Preprint alert - this is a big one! We transfer the revolutionary power of TnSeq to bacteriophages.
Our HIDEN-SEQ links the "dark matter" genes of your favorite phage to any selectable phenotype, guiding the path from fun observations to molecular mechanisms.
A thread 1/8
20.11.2025 20:39 β
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Iβm excited to share my recent postdoc work. Here, we interrogate how different phage infection outcomes (productive vs. restrictive) affect the expression of phage defense systems. We find that a restricted infection not only inhibits the phage but also induces increased immune protein abundance.
15.11.2025 18:10 β
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Surviving phage attack dynamically regulates bacterial immunity to defeat counterdefenses https://www.biorxiv.org/content/10.1101/2025.11.13.688357v1
15.11.2025 00:17 β
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Cap1 forms a cyclic tetra-adenylate-induced membrane pore during the type III-A CRISPR-Cas immune response https://www.biorxiv.org/content/10.1101/2025.11.13.688252v1
14.11.2025 02:18 β
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Scalable and systematic hierarchical virus taxonomy with vConTACT3
Viruses are key players in diverse ecosystems, but studying their impacts is technically and taxonomically challenging. Taxonomic complexities derive from undersampling, diverse DNA and RNA genomes wi...
π¨vConTACT3 preprint live!π¨(Peer Review soon...!)
vConTACT3 delivers a unified, scalable, and transparent framework for genome-based virus taxonomy β helping translate big viral data into systematic classification.
π Read the preprint: doi.org/10.1101/2025...
Improvements details below π
07.11.2025 16:36 β
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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
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A membrane-bound nuclease directly cleaves phage DNA during genome injection https://www.biorxiv.org/content/10.1101/2025.11.03.685801v1
03.11.2025 16:16 β
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Been working on a really strange retron bacterial immune system, here's the preprint: www.biorxiv.org/content/10.1...
Type VI retrons are unlike any other. Phage infection triggers reverse transcription of a DNA fragment that activates translation of a toxin to kill the infected cell.
23.10.2025 18:49 β
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Two intensive sampling periods of oyster-associated vibrio and their phage, 4 years apart, and many surprises. Despite being washed by the Atlantic, wide tides, and vibrio (almost?) disappearing most of the year, we can find the exact same virulent phages 4 years later (down to 0 SNP)! preprintπ
14.10.2025 16:07 β
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Happy that the final version of our Lamassu work @yli18smc.bsky.social is now out:
www.nature.com/articles/s41...
Thanks again to our awesome collaborators @mblokesch.bsky.social and David and co and Mark Szczelkun and @steven-shaw.bsky.social and the DCI Lausanne @fbm-unil.bsky.social
14.10.2025 09:28 β
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How do SMC complexes load onto DNA to get ready for loop extrusion?
@roisnehamelinf.bsky.social & co discovered that Wadjet, an SMC complex involved in bacterial DNA immunity, performs some impressive molecular gymnastics π€ΈββοΈπ€ΈββοΈπ€ΈββοΈ.
Check out the new paper: www.cell.com/molecular-ce...
09.10.2025 14:43 β
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