title: GipA Factor Supports Colonization of Peyer's Patches by Crohn's Disease-associated Escherichia Coli.
abstract: BACKGROUND
  Adherent-invasive Escherichia coli (AIEC) associated with Crohn's disease target M cells lining Peyer's patches (PPs) through the expression of long polar fimbriae (LPF) and survive macrophage killing. Invasion of PPs constitutes a way to colonize the mucosa for bacteria able to escape or resist killing of underlying immune cells. We aimed to identify new virulence factors involved in PPs colonization by AIEC.
  
  
  METHODS
  The presence of gipA (Growth in PPs) gene was determined by polymerase chain reaction. In vivo experiments were performed using CEABAC10 transgenic mice. Intramacrophagic behavior of AIEC was assessed in murine bone marrow-derived macrophages and human monocyte-derived macrophages. Cytokines production was quantified by ELISA.
  
  
  RESULTS
  A higher prevalence of gipA-positive E. coli was observed in patients with Crohn's disease (27.3%) compared with controls (17.2%). Unlike non-AIEC strains, all gipA-positive AIEC strains also harbored lpfA. GipA deletion impaired AIEC translocation across M cells and their replication inside macrophages. GipA expression was induced by gastrointestinal (bile salts) and phagolysosomal (reactive oxygen species and acid pH) conditions. GipA deletion decreased lpfA mRNA level in AIEC bacteria. Survival of AIEC-ΔgipA bacteria was reduced in medium containing H2O2 or acidic pH. GipA deletion impaired AIEC colonization of PPs and dissemination to mesenteric lymph nodes in mice.
  
  
  CONCLUSIONS
  GipA is required for optimal colonization of mouse PPs and survival within macrophages by AIEC, suggesting that this factor plays a role in AIEC promotion of Crohn's disease. Detection of gipA and lpfA could be a predictor for the presence of AIEC.
authors.affiliation: *UMR1071 Inserm/University of Auvergne, INRA USC2018, M2iSH, Clermont-Ferrand, France; †Department of Hepato-Gastroenterology, University Hospital Estaing, Clermont-Ferrand, France; ‡Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia; §Inserm U995, University Lille II, Hospital Claude Huriez, Lille, France; ‖Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York; and ¶INRA UMR1324, CNRS UMR6265, University Bourgogne-Franche-Comté, Centre des Sciences du Goût et de l'Alimentation, Dijon, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Vazeille
authors.forename: Benoit
authors.initials: B
authors.lastname: Chassaing
authors.forename: Anthony
authors.initials: A
authors.lastname: Buisson
authors.forename: Anaëlle
authors.initials: A
authors.lastname: Dubois
authors.forename: Amélie
authors.initials: A
authors.lastname: de Vallée
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Billard
authors.forename: Christel
authors.initials: C
authors.lastname: Neut
authors.forename: Gilles
authors.initials: G
authors.lastname: Bommelaer
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Colombel
authors.forename: Nicolas
authors.initials: N
authors.lastname: Barnich
authors.forename: Arlette
authors.initials: A
authors.lastname: Darfeuille-Michaud
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Bringer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001422:Bacterial Adhesion; D016022:Case-Control Studies; D003424:Crohn Disease / Q000150:complications / Q000378:metabolism* / Q000382:microbiology; D004926:Escherichia coli / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D010861:Fimbriae, Bacterial / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005500:Follow-Up Studies; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D010581:Peyer's Patches / Q000378:metabolism / Q000382:microbiology*; D017386:Sequence Homology, Amino Acid; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D037521:Virulence Factors