Bacteriophage defends murine gut from Escherichia coli invasion via mucosal adherence

Area of Science:

• Microbiology
• Gastroenterology
• Biotechnology

Background:

• Bacteriophages (phages) are viruses that infect bacteria.
• Phages interacting with mammalian hosts, particularly the gut, are gaining attention.
• Phage adherence to mucus enhances antimicrobial activity in vitro, but in vivo efficacy is less understood.

Purpose of the Study:

• To evaluate the therapeutic efficacy of mucus-adherent phages in vivo.
• To investigate the interaction between bacteriophage øPNJ-6, gut mucus, and host response.
• To explore the potential of mucus-adherent phages for enhanced phage therapy.

Main Methods:

• In vitro studies using gastrointestinal cell lines.
• Gut-on-a-chip microfluidic model.
• In vivo murine gut model to assess phage persistence and antimicrobial effects.

Main Results:

• Phage øPNJ-6 demonstrated enhanced gastrointestinal persistence and antimicrobial effects in a murine model.
• øPNJ-6 specifically bound to fucose residues on MUC2 via its Hoc protein domain 1.
• Phage adherence induced increased intestinal mucus production, suggesting a positive feedback loop.

Conclusions:

• Mucus-adherent bacteriophages can exhibit improved persistence and therapeutic efficacy in the gastrointestinal tract.
• The interaction between phage øPNJ-6 and MUC2 highlights a mechanism for enhanced phage therapy.
• Findings support the Bacteriophage Adherence to Mucus model for in vivo phage therapy applications.