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Supramolecular discrimination and diagnosis-guided treatment of intracellular bacteria

Author

Listed:
  • Jia-Hong Tian

    (Nankai University
    Nankai University
    Nankai University
    Nankai University)

  • Siyuan Huang

    (Nankai University
    Nankai University
    Nankai University)

  • Ze-Han Wang

    (Nankai University
    Nankai University
    Nankai University
    Nankai University)

  • Juan-Juan Li

    (Nankai University
    Nankai University
    Nankai University
    Nankai University)

  • Xianhui Song

    (Nankai University
    Nankai University
    Nankai University)

  • Ze-Tao Jiang

    (Nankai University
    Nankai University
    Nankai University
    Nankai University)

  • Bing-Sen Shi

    (Hebei University
    Hebei University
    Hebei University
    Hebei University)

  • Ying-Ying Zhao

    (Hebei University
    Hebei University
    Hebei University
    Hebei University)

  • Hui-Yan Zhang

    (Hebei University
    Hebei University
    Hebei University
    Hebei University)

  • Ke-Rang Wang

    (Hebei University
    Hebei University
    Hebei University
    Hebei University)

  • Xin-Yue Hu

    (Nankai University
    Nankai University
    Nankai University
    Nankai University)

  • Xinge Zhang

    (Nankai University
    Nankai University
    Nankai University)

  • Dong-Sheng Guo

    (Nankai University
    Nankai University
    Nankai University
    Nankai University)

Abstract

Pathogenic intracellular bacteria pose a significant threat to global public health due to the barriers presented by host cells hindering the timely detection of hidden bacteria and the effective delivery of therapeutic agents. To address these challenges, we propose a tandem diagnosis-guided treatment paradigm. A supramolecular sensor array is developed for simple, rapid, accurate, and high-throughput identification of intracellular bacteria. This diagnostic approach executes the significant guiding missions of screening a customized host-guest drug delivery system by disclosing the rationale behind the discrimination. We design eight azocalix[4]arenes with differential active targeting, cellular internalization, and hypoxia responsiveness to penetrate cells and interact with bacteria. Loaded with fluorescent indicators, these azocalix[4]arenes form a sensor array capable of discriminating eight intracellular bacterial species without cell lysis or separation. By fingerprinting specimens collected from bacteria-infected mice, the facilitated accurate diagnosis offers valuable guidance for selecting appropriate antibiotics. Moreover, mannose-modified azocalix[4]arene (ManAC4A) is screened as a drug carrier efficiently taken up by macrophages. Doxycycline loaded with ManAC4A exhibits improved efficacy against methicillin-resistant Staphylococcus aureus-infected peritonitis. This study introduces an emerging paradigm to intracellular bacterial diagnosis and treatment, offering broad potential in combating bacterial infectious diseases.

Suggested Citation

  • Jia-Hong Tian & Siyuan Huang & Ze-Han Wang & Juan-Juan Li & Xianhui Song & Ze-Tao Jiang & Bing-Sen Shi & Ying-Ying Zhao & Hui-Yan Zhang & Ke-Rang Wang & Xin-Yue Hu & Xinge Zhang & Dong-Sheng Guo, 2025. "Supramolecular discrimination and diagnosis-guided treatment of intracellular bacteria," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56308-9
    DOI: 10.1038/s41467-025-56308-9
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    References listed on IDEAS

    as
    1. Sophie M. Lehar & Thomas Pillow & Min Xu & Leanna Staben & Kimberly K. Kajihara & Richard Vandlen & Laura DePalatis & Helga Raab & Wouter L. Hazenbos & J. Hiroshi Morisaki & Janice Kim & Summer Park &, 2015. "Novel antibody–antibiotic conjugate eliminates intracellular S. aureus," Nature, Nature, vol. 527(7578), pages 323-328, November.
    2. Juan-Juan Li & Yuqing Hu & Bing Hu & Wenbo Wang & Haiqi Xu & Xin-Yue Hu & Fei Ding & Hua-Bin Li & Ke-Rang Wang & Xinge Zhang & Dong-Sheng Guo, 2022. "Lactose azocalixarene drug delivery system for the treatment of multidrug-resistant pseudomonas aeruginosa infected diabetic ulcer," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Jia-Hong Tian & Xin-Yue Hu & Zong-Ying Hu & Han-Wen Tian & Juan-Juan Li & Yu-Chen Pan & Hua-Bin Li & Dong-Sheng Guo, 2022. "A facile way to construct sensor array library via supramolecular chemistry for discriminating complex systems," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
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