Academic Journal
A membrane-bound nuclease directly cleaves phage DNA during genome injection.
| Title: | A membrane-bound nuclease directly cleaves phage DNA during genome injection. |
|---|---|
| Authors: | Saxton DS; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., DeWeirdt PC; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.; Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA, USA., Doering CR; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., Roney IJ; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., Laub MT; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. laub@mit.edu.; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA. laub@mit.edu. |
| Source: | Nature [Nature] 2026 May; Vol. 653 (8115), pp. 861-869. Date of Electronic Publication: 2026 Feb 25. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE |
| Imprint Name(s): | Publication: Basingstoke : Nature Publishing Group Original Publication: London, Macmillan Journals ltd. |
| MeSH Terms: | Bacteriophage lambda*/genetics , Bacteriophage lambda*/physiology , DNA, Viral*/metabolism , DNA, Viral*/genetics , Escherichia coli*/virology , Escherichia coli*/enzymology , Escherichia coli*/cytology , Escherichia coli*/metabolism, Cell Membrane/enzymology ; Cell Membrane/metabolism ; Escherichia coli Proteins/metabolism ; DNA Cleavage ; Genome, Viral |
| Abstract: | From mammals to bacteria, the direct recognition and cleavage of viral nucleic acids is a potent defence strategy against viral infection, but it requires mechanisms for distinguishing self from non-self1,2. In bacteria, CRISPR-Cas and restriction-modification systems achieve this discrimination by recognizing specific DNA sequences or DNA modifications, respectively. Alternative mechanisms probably remain to be discovered. Here, we characterize SNIPE, an anti-bacteriophage defence system that constitutively localizes to the bacterial cell membrane in Escherichia coli to block phage λ infection. Using radiolabelled phage DNA and time-lapse microscopy to track phage genomes, we demonstrate that SNIPE directly cleaves phage DNA during genome injection. Based on proximity labelling, we find that SNIPE associates with host proteins essential for λ genome entry and with the λ tape measure protein, which facilitates λ genome injection across the inner membrane. SNIPE also defends against diverse siphoviruses, probably through direct interactions with their tape measure proteins. Our findings establish SNIPE as a widespread bacterial defence system that exploits the spatial organization of phage genome injection to specifically target viral DNA, representing a previously unknown strategy for distinguishing self from non-self in prokaryotic immune systems. (© 2026. The Author(s).) |
| Competing Interests: | Competing interests: The authors declare no competing interests. |
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| Substance Nomenclature: | 0 (DNA, Viral) 0 (Escherichia coli Proteins) |
| Entry Date(s): | Date Created: 20260225 Date Completed: 20260521 Latest Revision: 20260523 |
| Update Code: | 20260523 |
| PubMed Central ID: | PMC13190303 |
| DOI: | 10.1038/s41586-026-10207-1 |
| PMID: | 41741653 |
| Database: | MEDLINE |
| ISSN: | 1476-4687 |
|---|---|
| DOI: | 10.1038/s41586-026-10207-1 |