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T4 Bacteriophage and E. coli Interaction in the Murine Intestine: A Prototypical Model for Studying Host-Bacteriophage Dynamics In Vivo
08:46

T4 Bacteriophage and E. coli Interaction in the Murine Intestine: A Prototypical Model for Studying Host-Bacteriophage Dynamics In Vivo

Published on: January 26, 2024

Virulent bacteriophages can target O104:H4 enteroaggregative Escherichia coli in the mouse intestine

Damien Maura1, Matthieu Galtier, Chantal Le Bouguénec

  • 1Department of Microbiology, Institut Pasteur, Molecular Biology of the Gene in Extremophiles Unit, Paris, France.

Antimicrobial Agents and Chemotherapy
|September 26, 2012
PubMed

Insights

Bacteriophage therapy targeting enteroaggregative Escherichia coli (EAEC) showed transient reductions in mouse models. Bacterial permissivity to phages varied between gut locations, impacting treatment effectiveness.

Area of Science:

  • Microbiology
  • Gastroenterology
  • Infectious Diseases

Background:

  • Enteroaggregative Escherichia coli (EAEC) is an intestinal pathogen.
  • Bacteriophage therapy is a promising alternative to antibiotics for bacterial infections.
  • Understanding phage-host interactions in vivo is crucial for therapeutic development.

Purpose of the Study:

  • To assess in vivo bacteriophage targeting of EAEC O104:H4 55989Str using a mouse intestinal colonization model.
  • To investigate the dose-dependent efficacy and duration of phage therapy.
  • To determine the influence of gut location on bacterial permissivity to bacteriophages.

Main Methods:

  • A mouse intestinal colonization model was established with EAEC O104:H4 55989Str.
  • A cocktail of three virulent bacteriophages was administered via drinking water.
  • Bacterial concentrations in ileal and fecal samples were quantified.
  • Experiments were conducted in both conventional and axenic mice to assess microbiota independence.
  • Bacteriophage infectivity and bacterial permissivity were evaluated in different gut segments.

Main Results:

  • Phage cocktail administration significantly reduced ileal and weakly reduced fecal EAEC concentrations in a dose-dependent manner.
  • These reductions were transient, with bacterial levels returning to baseline within 3 days.
  • The observed decreases were independent of the host's microbiota.
  • Bacterial permissivity to phage infection differed significantly between the ileum (permissive to all three phages) and feces (permissive to only one).

Conclusions:

  • Bacterial permissivity to bacteriophage infection is not uniform throughout the gastrointestinal tract.
  • This heterogeneity in phage infectivity poses challenges for developing effective phage therapy targeting intestinal pathogens.
  • Further characterization of in vivo host-phage interactions is necessary for optimizing phage therapy strategies.

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