{
  "abstract": "To fully harness phage therapy against escalating antimicrobial resistance, it is imperative to elucidate the fundamental mechanisms by which viruses systematically dismantle host physiology. In this study, we identify Ped1, a protein from Pseudomonas aeruginosa phage PaoP5, which suppresses bacterial growth through two mechanisms: degradation of genomic DNA and direct inhibition of the replication machinery. Our 2.3-Å crystal structure and biochemical profiling reveal that Ped1 adopts a previously uncharacterized α/β-nuclease architecture, enabling the efficient cleavage of both double-stranded and single-stranded DNA. Furthermore, we demonstrate that Ped1 physically interacts with the host replicative helicase, DnaB, to suppress its activity during DNA replication. Reciprocally, DnaB binds Ped1 to neutralize its nuclease function, acting as an internal immunity partner. Evolutionary analysis indicates that Ped1 is a lineage-specific toxin strictly conserved among Pseudomonas phages. Collectively, this work identifies a novel, dual-function phage effector that coordinately disrupts genomic integrity and replication fidelity, thus advancing our understanding of the phage–host molecular arms race, and describing a promising scaffold for the development of next-generation antimicrobials against multidrug-resistant P. aeruginosa.",
  "abstract_shown": true,
  "affiliations": [
    "Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, China",
    "Department of Biochemistry, SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China",
    "School of Basic Medical Science, Xi’an Medical University, Xi’an, China",
    "Department of Microbiology, Army Medical University, Chongqing, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Tietao Wang",
      "orcid": "0000-0001-8540-436X"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenbo Yan",
      "orcid": "0009-0007-5439-274X"
    },
    {
      "affs": [
        1
      ],
      "name": "Chenchen Wang",
      "orcid": "0000-0002-3618-1670"
    },
    {
      "affs": [
        1
      ],
      "name": "Longgang Sang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yingxin Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingru Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Chao Li"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Lijun Liu",
      "orcid": "0009-0003-7686-1405"
    },
    {
      "affs": [
        0
      ],
      "name": "Yani Zhang"
    },
    {
      "affs": [
        3
      ],
      "name": "Shuai Le",
      "orcid": "0000-0003-3748-5454"
    },
    {
      "affs": [
        1
      ],
      "name": "Haihua Liang",
      "orcid": "0009-0006-3266-8197"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3mxftkgby6nkk.bib",
  "cited_by": 0,
  "doi": "10.1038/s44318-026-00924-8",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13728149/",
  "id": "3mxftkgby6nkk",
  "issns": [
    "0261-4189",
    "1460-2075"
  ],
  "landing_url": "https://doi.org/10.1038/s44318-026-00924-8",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2303|Bacteriophages and microbial interactions"
    ]
  ],
  "openalex": "W7216124368",
  "pdf_url": "https://link.springer.com/content/pdf/10.1038/s44318-026-00924-8.pdf",
  "pmcid": "PMC13728149",
  "pmid": "42827202",
  "published": "2026-10-02",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/3mxftkgby6nkk.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:23:53Z",
      "native_id": "PMC13728149",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s44318-026-00924-8"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2303|Bacteriophages and microbial interactions",
      "subfield": "ecology"
    }
  ],
  "title": "A dual-action bacteriophage protein Ped1 degrades DNA and blocks replication in Pseudomonas aeruginosa",
  "title_text": "A dual-action bacteriophage protein Ped1 degrades DNA and blocks replication in Pseudomonas aeruginosa",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:11Z",
  "url": "https://research.draconitic.com/paper/3mxftkgby6nkk",
  "venue": "The EMBO Journal",
  "versions": []
}