{
  "abstract": "Bacteria and bacteriophages are in a constant arms race to develop defence and anti-defence systems, respectively. Currently known phage-encoded anti-defence systems are specific to the activity of the targeted bacterial defence system. Here we identify a mechanism by which the T7 bacteriophage broadly counteracts bacterial defences using protein phosphorylation. Its kinase (T7K), which has been reported to redirect the function of a few host proteins 1–5 , is actually a hyperpromiscuous dual-specificity kinase that phosphorylates nearly all host and phage proteins during infection. The scale of phosphorylation vastly exceeds known phosphosites in Escherichia coli , has no sequence motif specificity and results in a higher proteome-wide phosphorylation density than mammalian cells with around 500 kinases. Stoichiometry analysis of phosphorylation sites revealed strong bias in T7K activity towards nucleic-acid-binding substrates mediated by its C-terminal DNA-binding domain. This highly stoichiometric phosphorylation enables the deactivation of DNA-targeting or DNA-containing bacterial defence systems. We provide mechanistic insights into how T7K weakens DNA-containing Retron-Eco9 through specific phosphorylation events, with single phosphomimetic mutations in key sites of the toxin abolishing defence. Moreover, by screening a large collection of E. coli strains, we provide evidence of broad anti-defence abilities of T7K in nature, as counteracted strains contain diverse bacterial defence systems. T7K homologues are found almost exclusively in phages, with hyperpromiscuous kinase activity probably being enabled by a divergent DFG-like motif in the catalytic centre.",
  "abstract_shown": true,
  "affiliations": [
    "Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany",
    "Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany",
    "Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences, Heidelberg, Germany",
    "Microbial Automation & Culturomics Core Facility, European Molecular Biology Laboratory, Heidelberg, Germany",
    "Division of Microbial Ecology, Centre for Microbiology and Environmental Systems Science, University of Vienna, Vienna, Austria",
    "Florida Research and Innovation Center, Cleveland Clinic, Port St Lucie, FL, USA",
    "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School (MHH), Hannover, Germany",
    "Institute for Molecular Bacteriology, TWINCORE Centre for Experimental and Clinical Infection Research, Hannover, Germany",
    "Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. athanasios.typas@embl.de",
    "Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. athanasios.typas@embl.de",
    "Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. mikhail.savitski@embl.de",
    "Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. mikhail.savitski@embl.de"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Tara K. Bartolec",
      "orcid": "0000-0002-5291-6972"
    },
    {
      "affs": [
        1
      ],
      "name": "Karin Mitosch",
      "orcid": "0000-0002-9086-3277"
    },
    {
      "affs": [
        0
      ],
      "name": "Clément M. Potel",
      "orcid": "0000-0003-3655-4665"
    },
    {
      "affs": [
        0
      ],
      "name": "Federico Corona",
      "orcid": "0000-0002-0743-5520"
    },
    {
      "affs": [
        2,
        0
      ],
      "name": "Alessio Ling Jie Yang",
      "orcid": "0000-0003-4981-872X"
    },
    {
      "affs": [
        0
      ],
      "name": "Nicolai Karcher",
      "orcid": "0000-0001-7894-8182"
    },
    {
      "affs": [
        2,
        0
      ],
      "name": "Mira Lea Burtscher",
      "orcid": "0000-0003-2628-0795"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Alexandra Koumoutsi",
      "orcid": "0000-0001-8368-4193"
    },
    {
      "affs": [
        0
      ],
      "name": "Isabelle Becher",
      "orcid": "0000-0001-7170-2235"
    },
    {
      "affs": [
        0
      ],
      "name": "Lena Sarah Müller"
    },
    {
      "affs": [
        4,
        1
      ],
      "name": "Jacob Bobonis",
      "orcid": "0000-0001-9293-9733"
    },
    {
      "affs": [
        5,
        0
      ],
      "name": "Manjeet Kumar",
      "orcid": "0000-0002-3004-2151"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Marco Galardini",
      "orcid": "0000-0003-2018-8242"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Athanasios Typas",
      "orcid": "0000-0002-0797-9018"
    },
    {
      "affs": [
        10,
        11
      ],
      "name": "Mikhail M. Savitski",
      "orcid": "0000-0003-2011-9247"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bjdmnvddxzy8c.bib",
  "cited_by": 9,
  "doi": "10.1038/s41586-026-10934-5",
  "fulltext_url": null,
  "id": "bjdmnvddxzy8c",
  "issns": [
    "0028-0836",
    "1476-4687"
  ],
  "landing_url": "https://doi.org/10.1038/s41586-026-10934-5",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2303|Bacteriophages and microbial interactions"
    ],
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      "openalex",
      "2406|Bacteriophages and microbial interactions"
    ]
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  "openalex": "W7203785243",
  "pdf_url": null,
  "pmcid": "PMC13645617",
  "pmid": "42618789",
  "published": "2026-08-19",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/bjdmnvddxzy8c.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T13:21:16Z",
      "native_id": "W7203785243",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41586-026-10934-5"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2303|Bacteriophages and microbial interactions",
      "subfield": "ecology"
    },
    {
      "field": "biology",
      "origin": "openalex:2406|Bacteriophages and microbial interactions",
      "subfield": "microbiology"
    }
  ],
  "title": "Pervasive phosphorylation by phage T7 kinase disarms bacterial defences",
  "title_text": "Pervasive phosphorylation by phage T7 kinase disarms bacterial defences",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:46Z",
  "url": "https://research.draconitic.com/paper/bjdmnvddxzy8c",
  "venue": "Nature",
  "versions": []
}