title: Virulent bacteriophages can target O104:H4 enteroaggregative Escherichia coli in the mouse intestine.
abstract: In vivo bacteriophage targeting of enteroaggregative Escherichia coli (EAEC) was assessed using a mouse intestinal model of colonization with the O104:H4 55989Str strain and a cocktail of three virulent bacteriophages. The colonization model was shown to mimic asymptomatic intestinal carriage found in humans. The addition of the cocktail to drinking water for 24 h strongly decreased ileal and weakly decreased fecal 55989Str concentrations in a dose-dependent manner. These decreases in ileal and fecal bacterial concentrations were only transient, since 55989Str concentrations returned to their original levels 3 days later. These transient decreases were independent of the mouse microbiota, as similar results were obtained with axenic mice. We studied the infectivity of each bacteriophage in the ileal and fecal environments and found that 55989Str bacteria in the mouse ileum were permissive to all three bacteriophages, whereas those in the feces were permissive to only one bacteriophage. Our results provide the first demonstration that bacterial permissivity to infection with virulent bacteriophages is not uniform throughout the gut; this highlights the need for a detailed characterization of the interactions between bacteria and bacteriophages in vivo for the further development of phage therapy targeting intestinal pathogens found in the gut of asymptomatic human carriers.
authors.affiliation: Department of Microbiology, Institut Pasteur, Molecular Biology of the Gene in Extremophiles Unit, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Maura
authors.forename: Matthieu
authors.initials: M
authors.lastname: Galtier
authors.forename: Chantal
authors.initials: C
authors.lastname: Le Bouguénec
authors.forename: Laurent
authors.initials: L
authors.lastname: Debarbieux
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001435:Bacteriophages / Q000187:drug effects / Q000502:physiology*; D003106:Colon / Q000382:microbiology / Q000473:pathology; D004926:Escherichia coli / Q000821:virology*; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D005260:Female; D007082:Ileum / Q000382:microbiology / Q000473:pathology; D007150:Immunohistochemistry; D007410:Intestinal Diseases / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016133:Polymerase Chain Reaction; D014779:Virus Replication