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Bacteriophage defends murine gut from Escherichia coli invasion via mucosal adherence

Author

Listed:
  • Jiaoling Wu

    (Ministry of Agriculture)

  • Kailai Fu

    (Ministry of Agriculture)

  • Chenglin Hou

    (Ministry of Agriculture)

  • Yuxin Wang

    (Ministry of Agriculture)

  • Chengyuan Ji

    (Ministry of Agriculture)

  • Feng Xue

    (Ministry of Agriculture)

  • Jianluan Ren

    (Ministry of Agriculture)

  • Jianjun Dai

    (Ministry of Agriculture
    Ministry of Education (ERCADD))

  • Jeremy J. Barr

    (Monash University)

  • Fang Tang

    (Ministry of Agriculture)

Abstract

Bacteriophage are sophisticated cellular parasites that can not only parasitize bacteria but are increasingly recognized for their direct interactions with mammalian hosts. Phage adherence to mucus is known to mediate enhanced antimicrobial effects in vitro. However, little is known about the therapeutic efficacy of mucus-adherent phages in vivo. Here, using a combination of in vitro gastrointestinal cell lines, a gut-on-a-chip microfluidic model, and an in vivo murine gut model, we demonstrated that a E. coli phage, øPNJ-6, provided enhanced gastrointestinal persistence and antimicrobial effects. øPNJ-6 bound fucose residues, of the gut secreted glycoprotein MUC2, through domain 1 of its Hoc protein, which led to increased intestinal mucus production that was suggestive of a positive feedback loop mediated by the mucus-adherent phage. These findings extend the Bacteriophage Adherence to Mucus model into phage therapy, demonstrating that øPNJ-6 displays enhanced persistence within the murine gut, leading to targeted depletion of intestinal pathogenic bacteria.

Suggested Citation

  • Jiaoling Wu & Kailai Fu & Chenglin Hou & Yuxin Wang & Chengyuan Ji & Feng Xue & Jianluan Ren & Jianjun Dai & Jeremy J. Barr & Fang Tang, 2024. "Bacteriophage defends murine gut from Escherichia coli invasion via mucosal adherence," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48560-2
    DOI: 10.1038/s41467-024-48560-2
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    References listed on IDEAS

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    1. Yi Duan & Cristina Llorente & Sonja Lang & Katharina Brandl & Huikuan Chu & Lu Jiang & Richard C. White & Thomas H. Clarke & Kevin Nguyen & Manolito Torralba & Yan Shao & Jinyuan Liu & Adriana Hernand, 2019. "Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease," Nature, Nature, vol. 575(7783), pages 505-511, November.
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