Intestinal colonization by enteroaggregative Escherichia coli supports long-term bacteriophage replication in mice

Authors

  • Damien Maura,

    1. Institut Pasteur, Molecular Biology of the Gene in Extremophiles Unit, Department of Microbiology, F-75015 Paris, France.
    2. Univ. Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, rue du Docteur. Roux, F-75015 Paris, France.
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  • Eric Morello,

    1. Institut Pasteur, Molecular Biology of the Gene in Extremophiles Unit, Department of Microbiology, F-75015 Paris, France.
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  • Laurence du Merle,

    1. Institut Pasteur, Biology of Gram Positive Pathogens Unit, Department of Microbiology, F-75015 Paris, France.
    2. CNRS URA2172, F-75015 Paris, France.
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  • Perrine Bomme,

    1. Institut Pasteur, PFMU, Imagopole, F-75015 Paris, France.
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  • Chantal Le Bouguénec,

    1. Institut Pasteur, Biology of Gram Positive Pathogens Unit, Department of Microbiology, F-75015 Paris, France.
    2. CNRS URA2172, F-75015 Paris, France.
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  • Laurent Debarbieux

    Corresponding author
    1. Institut Pasteur, Molecular Biology of the Gene in Extremophiles Unit, Department of Microbiology, F-75015 Paris, France.
      E-mail laurent.debarbieux@pasteur.fr; Tel. (+33) 1 4438 92 03; Fax (+33) 1 45 68 88 34.
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E-mail laurent.debarbieux@pasteur.fr; Tel. (+33) 1 4438 92 03; Fax (+33) 1 45 68 88 34.

Summary

Bacteriophages have been known to be present in the gut for many years, but studies of relationships between these viruses and their hosts in the intestine are still in their infancy. We isolated three bacteriophages specific for an enteroaggregative O104:H4 Escherichia coli (EAEC) strain responsible for diarrhoeal diseases in humans. We studied the replication of these bacteriophages in vitro and in vivo in a mouse model of gut colonization. Each bacteriophage was able to replicate in vitro in both aerobic and anaerobic conditions. Each bacteriophage individually reduced biofilms formed on plastic pegs and a cocktail of the three bacteriophages was found to be more efficient. The cocktail was also able to infect bacterial aggregates formed on the surface of epithelial cells. In the mouse intestine, bacteriophages replicated for at least 3 weeks, provided the host was present, with no change in host levels in the faeces. This model of stable and continuous viral replication provides opportunities for studying the long-term coevolution of virulent bacteriophages with their hosts within a mammalian polymicrobial ecosystem.

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