The first two authors contributed equally to this work.
AIEC colonization and pathogenicity: Influence of previous antibiotic treatment and preexisting inflammation†
Article first published online: 16 FEB 2012
Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 18, Issue 10, pages 1923–1931, October 2012
How to Cite
Drouet, M., Vignal, C., Singer, E., Djouina, M., Dubreuil, L., Cortot, A., Desreumaux, P. and Neut, C. (2012), AIEC colonization and pathogenicity: Influence of previous antibiotic treatment and preexisting inflammation. Inflamm Bowel Dis, 18: 1923–1931. doi: 10.1002/ibd.22908
Supported by IRMAD/Astrazeneca, Association François Aupetit, HFSP.
- Issue published online: 13 SEP 2012
- Article first published online: 16 FEB 2012
- Manuscript Accepted: 16 JAN 2012
- Manuscript Received: 30 DEC 2011
- inflammatory bowel diseases;
- adherent-invasive E. coli;
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.
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.
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.
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)