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AIEC colonization and pathogenicity: Influence of previous antibiotic treatment and preexisting inflammation

Authors

  • Maryline Drouet PharmD,

    1. University Lille Nord de France, Lille, France
    2. Inserm U995, Lille, France
    3. UDSL, Laboratoire de Bactériologie Clinique, Lille, France
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    • The first two authors contributed equally to this work.

  • Cécile Vignal PhD,

    1. University Lille Nord de France, Lille, France
    2. Inserm U995, Lille, France
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    • The first two authors contributed equally to this work.

  • Elisabeth Singer PhD,

    1. University Lille Nord de France, Lille, France
    2. Inserm U995, Lille, France
    3. UDSL, Laboratoire de Bactériologie Clinique, Lille, France
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  • Madjid Djouina BS,

    1. University Lille Nord de France, Lille, France
    2. Inserm U995, Lille, France
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  • Luc Dubreuil PharmD, PhD,

    1. University Lille Nord de France, Lille, France
    2. Inserm U995, Lille, France
    3. UDSL, Laboratoire de Bactériologie Clinique, Lille, France
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  • Antoine Cortot MD,

    1. University Lille Nord de France, Lille, France
    2. Inserm U995, Lille, France
    3. CHRU Lille, Huriez Hospital, Hepato-Gastroenterology Department, Lille, France
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  • Pierre Desreumaux MD, PhD,

    1. University Lille Nord de France, Lille, France
    2. Inserm U995, Lille, France
    3. CHRU Lille, Huriez Hospital, Hepato-Gastroenterology Department, Lille, France
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  • Christel Neut PhD

    Corresponding author
    1. University Lille Nord de France, Lille, France
    2. Inserm U995, Lille, France
    3. UDSL, Laboratoire de Bactériologie Clinique, Lille, France
    • Laboratoire de Bactériologie Clinique, INSERM U995, Faculté de Pharmacie, 3, rue du Prof Laguesse, BP 83, 59006 Lille Cedex, France
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  • Supported by IRMAD/Astrazeneca, Association François Aupetit, HFSP.

Abstract

Background:

Inflammatory bowel diseases (IBD) patients are abnormally colonized by adherent-invasive Escherichia coli (AIEC). NOD2 gene mutations impair intracellular bacterial clearance. We evaluated the impact of antibiotic treatment on AIEC colonization in wildtype (WT) and NOD2 knockout mice (NOD2KO) and the consequences on intestinal inflammation.

Methods:

After 3 days of antibiotic treatment, mice were infected for 2 days with 109 CFU AIEC and sacrificed 1, 5, and 60 days later. In parallel, mice were challenged with AIEC subsequent to a dextran sodium sulfate (DSS) treatment and sacrificed 9 days later. Ileum, colon, and mesenteric tissues were sampled for AIEC quantification and evaluation of inflammation.

Results:

Without antibiotic treatment, AIEC was not able to colonize WT and NOD2KO mice. Compared with nontreated animals, antibiotic treatment led to a significant increase in ileal and colonic colonization of AIEC in WT and/or NOD2KO mice. Persistent AIEC colonization was observed until day 5 only in NOD2KO mice, disappearing at day 60. Mesenteric translocation of AIEC was observed only in NOD2KO mice. No inflammation was observed in WT and NOD2KO mice treated with antibiotics and infected with AIEC. During DSS-induced colitis, colonization and persistence of AIEC was observed in the colon. Moreover, a dramatic increase in clinical, histological, and molecular parameters of colitis was observed in mice infected with AIEC but not with a commensal E. coli strain.

Conclusions:

Antibiotic treatment was necessary for AIEC colonization of the gut and mesenteric tissues and persistence of AIEC was dependent on NOD2. AIEC exacerbated a preexisting DSS-induced colitis in WT mice. (Inflamm Bowel Dis 2012)

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