title: AIEC colonization and pathogenicity: influence of previous antibiotic treatment and preexisting inflammation.
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.
authors.affiliation: University Lille Nord de France, Lille, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Drouet
authors.forename: Cécile
authors.initials: C
authors.lastname: Vignal
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Singer
authors.forename: Madjid
authors.initials: M
authors.lastname: Djouina
authors.forename: Luc
authors.initials: L
authors.lastname: Dubreuil
authors.forename: Antoine
authors.initials: A
authors.lastname: Cortot
authors.forename: Pierre
authors.initials: P
authors.lastname: Desreumaux
authors.forename: Christel
authors.initials: C
authors.lastname: Neut
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects*; D018988:Bacterial Translocation / Q000187:drug effects; D015153:Blotting, Western; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000382:microbiology*; D016264:Dextran Sulfate / Q000633:toxicity; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053473:Nod2 Signaling Adaptor Protein / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000900:Anti-Bacterial Agents; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D012333:RNA, Messenger; D016264:Dextran Sulfate