{
  "abstract": "The biofilms of Mycobacterium Tuberculosis (Mtb) use extracellular DNA (eDNA) as a protective structural scaffold that shields resident bacteria from host immunity and antibiotics, promoting persistent infection. An FDA-approved DNase can partially hydrolyze eDNA but has limited affinity and nucleolytic activity against Z-form DNA (Z-DNA). After confirming the abundance of Z-DNA in Mtb biofilms, we develop Nano-NucleOTAC, a nano-nucleolysis targeting chimera that combines an eDNA-binding ligand (lactoferrin), a DNA intercalator (chloroquine) and DNase. Nano-NucleOTAC anchors to Z-DNA in Mtb H37Ra biofilms, enabling effective biofilm degradation via Z-DNA transformation and enzymatic cleavage. Following treatment, dispersed Mtb H37Ra clusters induce neutrophil extracellular trap (NET) formation and cytokine secretion (TNF, IL-1β, and IL-10) to recruit macrophages, while NET remodeling and nucleolysis enhance macrophage bactericidal effect vs. DNase alone. In mouse lung infection models, Nano-NucleOTAC improves lung drug retention, reduces pathology, and reactivates host immune responses. It also demonstrates high efficacy against Mtb strains of varying virulence (H37Ra, H37Rv) and non-tuberculous mycobacteria (Mycobacterium smegmatis). In clinical sputum samples, Nano-NucleOTAC potentiates rifampicin efficacy, and enhances neutrophil and macrophage antibacterial immunity in bronchoalveolar lavage fluid (BALF) and pus. This safe, versatile nucleic-acid-targeting strategy modulates bacterial biophysical barriers and host immunity to address biofilm-associated multidrug-resistant infections.",
  "abstract_shown": true,
  "affiliations": [
    "National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, China.",
    "National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, China. pengfeizhao@aliyun.com.",
    "The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University, Dongguan, China.",
    "National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, China. asakawat1971@gmail.com.",
    "National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, China. luhongzhou@fudan.edu.cn.",
    "National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, China. mingbinzheng@126.com.",
    "The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University, Dongguan, China. mingbinzheng@126.com.",
    "Guangdong Key Laboratory of Nanomedicine, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. mingbinzheng@126.com."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Deliang Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Pengfei Zhao",
      "orcid": "0000-0003-2034-7696"
    },
    {
      "affs": [
        0
      ],
      "name": "Yang Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhuojun He"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhiqiang Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Guiqin Dai"
    },
    {
      "affs": [
        0
      ],
      "name": "Senlin Shen"
    },
    {
      "affs": [
        0
      ],
      "name": "Yao Zhao",
      "orcid": "0000-0002-2932-2164"
    },
    {
      "affs": [
        0
      ],
      "name": "Pengqi Zhang"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Yuying Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Dongcheng Ren"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Jinzhi Pan"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiafei Dai"
    },
    {
      "affs": [
        3
      ],
      "name": "Tetsuya Asakawa",
      "orcid": "0000-0002-2300-3509"
    },
    {
      "affs": [
        4
      ],
      "name": "Hongzhou Lu"
    },
    {
      "affs": [
        5,
        6,
        7
      ],
      "name": "Mingbin Zheng",
      "orcid": "0000-0003-0463-7968"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6k3gtxtgdcfc8.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77825-1",
  "fulltext_url": "https://europepmc.org/articles/PMC13680464",
  "id": "6k3gtxtgdcfc8",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42897174",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2725|Tuberculosis Research and Epidemiology"
    ]
  ],
  "openalex": "W7213440726",
  "pdf_url": "https://europepmc.org/articles/PMC13680464?pdf=render",
  "pmcid": "PMC13680464",
  "pmid": "42897174",
  "published": "2026-09-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6k3gtxtgdcfc8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:41Z",
      "native_id": "MED:42897174",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42897174"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|Tuberculosis Research and Epidemiology",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Nano-NucleOTAC-mediated Z-DNA transformation disrupts mycobacterium tuberculosis biofilms and activates antibacterial immunity.",
  "title_text": "Nano-NucleOTAC-mediated Z-DNA transformation disrupts mycobacterium tuberculosis biofilms and activates antibacterial immunity.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:41Z",
  "url": "https://research.draconitic.com/paper/6k3gtxtgdcfc8",
  "venue": "Nature communications",
  "versions": []
}