2. Academic Validation
  3. Bacteriophage defends murine gut from Escherichia coli invasion via mucosal adherence

Bacteriophage defends murine gut from Escherichia coli invasion via mucosal adherence

  • Nat Commun. 2024 Jun 4;15(1):4764. doi: 10.1038/s41467-024-48560-2.
Jiaoling Wu 1,  Kailai Fu 1,  Chenglin Hou 1,  Yuxin Wang 1,  Chengyuan Ji 1,  Feng Xue 1,  Jianluan Ren 1,  Jianjun Dai 2 3,  Jeremy J Barr 4,  Fang Tang 5
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Nanjing Agricultural University; Key Laboratory of Animal Bacteriology, Ministry of Agriculture, Nanjing, China.
  • 2 College of Veterinary Medicine, Nanjing Agricultural University; Key Laboratory of Animal Bacteriology, Ministry of Agriculture, Nanjing, China. jjdai@njau.edu.cn.
  • 3 School of Pharmacy, China Pharmaceutical University; Engineering Research Center for Anti-infective Drug Discovery, Ministry of Education (ERCADD), Nanjing, China. jjdai@njau.edu.cn.
  • 4 School of Biological Sciences, Monash University, Victoria, Australia. jeremy.barr@monash.edu.
  • 5 College of Veterinary Medicine, Nanjing Agricultural University; Key Laboratory of Animal Bacteriology, Ministry of Agriculture, Nanjing, China. tfalice@126.com.
PMID: 38834561 DOI: 10.1038/s41467-024-48560-2
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.

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