Bacteriophage defends murine gut from Escherichia coli invasion via mucosal adherence

Jiaoling Wu, Kailai Fu, Chenglin Hou, Yuxin Wang, Chengyuan Ji, Feng Xue, Jianluan Ren, Jianjun Dai (), Jeremy J. Barr () and Fang Tang ()
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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
Jeremy J. Barr: Monash University
Fang Tang: Ministry of Agriculture

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-48560-2

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