{
  "abstract": "Bacterial defence systems are diverse and form major barriers to horizontal gene transfer and bacteriophage (phage) infection. Though restriction-modification systems were the first such defences discovered and remain the most widespread, the basis of self/non-self discrimination in many newly identified methylation-based systems remains unclear. Here, we define the mechanism of a widely distributed BREX-related defence family, previously termed Gao_RL, which we rename MANTIS (Methyltransferase, ATPases and Nuclease Targeting Inverted-repeat Sequences). Using phage infection and plasmid transformation assays in Pseudomonas aeruginosa, biochemical reconstitution, and structural biology, we show that MANTIS establishes self-identity through adenine hemimethylation of short asymmetric DNA sequences. Unexpectedly, a AAA+ ATPase (MtsA) and a co-regulator (MtsB) are both required to recruit and activate the methyltransferase MtsC, revealing a previously unknown ATP-dependent mode of epigenetic modification. DNA recognition by the MtsABC complex then triggers restriction by a dimeric helicase-nuclease effector (MtsD), with activity dependent on target-site architecture: inverted pairs of unmodified sites support robust restriction, whereas direct repeats or single sites are restricted less efficiently. Consistent with this model, virulent phages show strand-biased depletion of MANTIS target sites, indicating evolutionary pressure to evade restriction. Together, these findings reveal how dual ATPases couple self-modification to non-self restriction and provide a framework for understanding the expanding landscape of methylation-based defence systems.",
  "abstract_shown": true,
  "affiliations": [
    "University of Bristol"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "S. J. Shaw"
    },
    {
      "name": "S. C. Went"
    },
    {
      "name": "A. Agapov"
    },
    {
      "name": "J. Westley"
    },
    {
      "name": "A. Olina"
    },
    {
      "name": "S. Graham"
    },
    {
      "name": "C. E. Chong"
    },
    {
      "name": "MultiDefence Consortium"
    },
    {
      "name": "K. S. Baker"
    },
    {
      "name": "M. F. White"
    },
    {
      "name": "S. van Houte"
    },
    {
      "name": "E. R. Westra"
    },
    {
      "name": "T. R. Blower"
    },
    {
      "affs": [
        0
      ],
      "name": "M. D. Szczelkun"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/043rf573feymp.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.23.753747",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753747v1.full",
  "id": "043rf573feymp",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753747v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "molecular biology"
    ],
    [
      "openalex",
      "2303|Bacteriophages and microbial interactions"
    ]
  ],
  "openalex": "W7214222275",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753747v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/043rf573feymp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:20Z",
      "native_id": "10.64898/2026.09.23.753747",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753747v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Dual ATPase-activated DNA hemimethylation and cleavage by the MANTIS defence system",
  "title_text": "Dual ATPase-activated DNA hemimethylation and cleavage by the MANTIS defence system",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:20Z",
  "url": "https://research.draconitic.com/paper/043rf573feymp",
  "venue": "bioRxiv",
  "versions": []
}