GipA Factor Supports Colonization of Peyer's Patches by Crohn's Disease-associated Escherichia Coli

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-&Dgr;gipA 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.

[1]  J. Hugot,et al.  Monocyte-derived macrophages from Crohn's disease patients are impaired in the ability to control intracellular adherent-invasive Escherichia coli and exhibit disordered cytokine secretion profile. , 2015, Journal of Crohn's & colitis.

[2]  Michael J. Stanhope,et al.  Inflammation-associated Adherent-invasive Escherichia coli Are Enriched in Pathways for Use of Propanediol and Iron and M-cell Translocation , 2014, Inflammatory bowel diseases.

[3]  J. Boudeau,et al.  In Memoriam, Arlette Darfeuille-Michaud, PhD. , 2014, Gastroenterology.

[4]  B. Campbell,et al.  Escherichia coli-host macrophage interactions in the pathogenesis of inflammatory bowel disease. , 2014, World journal of gastroenterology.

[5]  David Artis,et al.  Intestinal epithelial cells: regulators of barrier function and immune homeostasis , 2014, Nature Reviews Immunology.

[6]  F. Seibold,et al.  Crohn's disease-associated adherent invasive Escherichia coli modulate levels of microRNAs in intestinal epithelial cells to reduce autophagy. , 2014, Gastroenterology.

[7]  D. Gordon,et al.  Detection of bacterial DNA in lymph nodes of Crohn's disease patients using high throughput sequencing , 2014, Gut.

[8]  David W. Holden,et al.  Internalization of Salmonella by Macrophages Induces Formation of Nonreplicating Persisters , 2014, Science.

[9]  B. Chassaing,et al.  Bile salts induce long polar fimbriae expression favouring Crohn's disease-associated adherent-invasive Escherichia coli interaction with Peyer's patches. , 2013, Environmental microbiology.

[10]  Richard Bonnet,et al.  Point Mutations in FimH Adhesin of Crohn's Disease-Associated Adherent-Invasive Escherichia coli Enhance Intestinal Inflammatory Response , 2013, PLoS pathogens.

[11]  J. Söderholm,et al.  Barrier dysfunction and bacterial uptake in the follicle‐associated epithelium of ileal Crohn's disease , 2012, Annals of the New York Academy of Sciences.

[12]  M. Bringer,et al.  Defects in autophagy favour adherent‐invasive Escherichia coli persistence within macrophages leading to increased pro‐inflammatory response , 2012, Cellular microbiology.

[13]  M. Bringer,et al.  Replication of Crohn's disease-associated AIEC within macrophages is dependent on TNF-α secretion , 2012, Laboratory Investigation.

[14]  C. Sasakawa,et al.  Shigella are versatile mucosal pathogens that circumvent the host innate immune system. , 2011, Current opinion in immunology.

[15]  Mark J. Pallen,et al.  Complete Genome Sequence of the Crohn's Disease-Associated Adherent-Invasive Escherichia coliStrain HM605 , 2011, Journal of bacteriology.

[16]  B. Chassaing,et al.  The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases. , 2011, Gastroenterology.

[17]  J. Hugot,et al.  Crohn disease--associated adherent-invasive E. coli bacteria target mouse and human Peyer's patches via long polar fimbriae. , 2011, The Journal of clinical investigation.

[18]  Annick Harel-Bellan,et al.  A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in Crohn's disease , 2011, Nature Genetics.

[19]  Andrew M Kropinski,et al.  Genome sequence of adherent-invasive Escherichia coli and comparative genomic analysis with other E. coli pathotypes , 2010, BMC Genomics.

[20]  Scot E. Dowd,et al.  Complete genome sequence of adherent invasive Escherichia coli UM146 isolated from Ileal Crohn's disease biopsy tissue. , 2011, Journal of bacteriology.

[21]  Eric Peyretaillade,et al.  Complete Genome Sequence of Crohn's Disease-Associated Adherent-Invasive E. coli Strain LF82 , 2010, PloS one.

[22]  N. Barnich,et al.  Abnormally expressed ER stress response chaperone Gp96 in CD favours adherent-invasive Escherichia coli invasion , 2010, Gut.

[23]  A. Macpherson,et al.  Immune adaptations that maintain homeostasis with the intestinal microbiota , 2010, Nature Reviews Immunology.

[24]  Jessica A. Thompson,et al.  Dynamics of intracellular bacterial replication at the single cell level , 2010, Proceedings of the National Academy of Sciences.

[25]  Maria T. Abreu,et al.  Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function , 2010, Nature Reviews Immunology.

[26]  R. Xavier,et al.  Crohn's disease‐associated adherent‐invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly , 2010, Cellular microbiology.

[27]  Shunsuke Kimura,et al.  Uptake through glycoprotein 2 of FimH+ bacteria by M cells initiates mucosal immune response , 2009, Nature.

[28]  A. Sivignon,et al.  Crohn's disease adherent-invasive Escherichia coli colonize and induce strong gut inflammation in transgenic mice expressing human CEACAM , 2009, The Journal of experimental medicine.

[29]  J. Blanco,et al.  Molecular diversity of Escherichia coli in the human gut: New ecological evidence supporting the role of adherent‐invasive E. coli (AIEC) in Crohn's disease , 2009, Inflammatory bowel diseases.

[30]  M. Vergassola,et al.  The Listeria transcriptional landscape from saprophytism to virulence , 2009, Nature.

[31]  Malina A. Bakowski,et al.  Salmonella‐Containing Vacuoles: Directing Traffic and Nesting to Grow , 2008, Traffic.

[32]  S. Edwards,et al.  Replication of Colonic Crohn's Disease Mucosal Escherichia coli Isolates within Macrophages and Their Susceptibility to Antibiotics , 2007, Antimicrobial Agents and Chemotherapy.

[33]  G. Dougan,et al.  Salmonella enterica Serovar Typhimurium Exploits Inflammation to Compete with the Intestinal Microbiota , 2007, PLoS biology.

[34]  J. Hugot,et al.  CARD15/NOD2 Is Required for Peyer's Patches Homeostasis in Mice , 2007, PloS one.

[35]  N. Barnich,et al.  CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease. , 2007, The Journal of clinical investigation.

[36]  M. Bringer,et al.  The Oxidoreductase DsbA Plays a Key Role in the Ability of the Crohn's Disease-Associated Adherent-Invasive Escherichia coli Strain LF82 To Resist Macrophage Killing , 2007, Journal of bacteriology.

[37]  T. Fuchs,et al.  Identification of novel genes in genomic islands that contribute to Salmonella typhimurium replication in macrophages. , 2007, Microbiology.

[38]  C. Tung,et al.  The Crohn's disease‐associated adherent‐invasive Escherichia coli strain LF82 replicates in mature phagolysosomes within J774 macrophages , 2006, Cellular microbiology.

[39]  N. Barnich,et al.  HtrA Stress Protein Is Involved in Intramacrophagic Replication of Adherent and Invasive Escherichia coli Strain LF82 Isolated from a Patient with Crohn's Disease , 2005, Infection and Immunity.

[40]  B. C. Wong,et al.  Evolutionary Dynamics of Insertion Sequences in Helicobacter pylori , 2004, Journal of bacteriology.

[41]  Laurent Beaugerie,et al.  High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. , 2004, Gastroenterology.

[42]  F. Shanahan,et al.  Bacterial DNA within Granulomas of Patients with Crohn's Disease—Detection by Laser Capture Microdissection and PCR , 2004, American Journal of Gastroenterology.

[43]  Y. Takesue,et al.  Bacterial Translocation in Patients With Crohn’s Disease Undergoing Surgery , 2002, Diseases of the colon and rectum.

[44]  A. West,et al.  Distribution of Peyer's Patches in the Distal Ileum , 2002, Inflammatory bowel diseases.

[45]  P. Sansonetti,et al.  Host–pathogen interactions: the seduction of molecular cross talk , 2002, Gut.

[46]  Jean-Frederic Colombel,et al.  Adherent Invasive Escherichia coli Strains from Patients with Crohn's Disease Survive and Replicate within Macrophages without Inducing Host Cell Death , 2001, Infection and Immunity.

[47]  Judy H. Cho,et al.  A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease , 2001, Nature.

[48]  Mourad Sahbatou,et al.  Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease , 2001, Nature.

[49]  J. Pak,et al.  Tamm-Horsfall Protein Binds to Type 1 Fimbriated Escherichia coli and Prevents E. coli from Binding to Uroplakin Ia and Ib Receptors* , 2001, The Journal of Biological Chemistry.

[50]  C. d’Enfert,et al.  A rapid method for efficient gene replacement in the filamentous fungus Aspergillus nidulans. , 2000, Nucleic acids research.

[51]  J. Slauch,et al.  Tissue-Specific Gene Expression Identifies a Gene in the Lysogenic Phage Gifsy-1 That Affects Salmonella enterica Serovar Typhimurium Survival in Peyer's Patches , 2000, Journal of bacteriology.

[52]  B. Wanner,et al.  One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[53]  J. Boudeau,et al.  Invasive Ability of an Escherichia coliStrain Isolated from the Ileal Mucosa of a Patient with Crohn’s Disease , 1999, Infection and Immunity.

[54]  P. Sansonetti,et al.  M cells as ports of entry for enteroinvasive pathogens: mechanisms of interaction, consequences for the disease process. , 1999, Seminars in immunology.

[55]  P. Sansonetti,et al.  Rupture of the intestinal epithelial barrier and mucosal invasion by Shigella flexneri. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[56]  N. Barnich,et al.  Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease. , 1998, Gastroenterology.

[57]  J. Kraehenbuhl,et al.  Conversion by Peyer's patch lymphocytes of human enterocytes into M cells that transport bacteria. , 1997, Science.

[58]  P. Sansonetti,et al.  Infection of rabbit Peyer's patches by Shigella flexneri: effect of adhesive or invasive bacterial phenotypes on follicle-associated epithelium , 1996, Infection and immunity.

[59]  D. Belin,et al.  Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter , 1995, Journal of bacteriology.

[60]  A. West,et al.  Immunocytochemical evidence of Listeria, Escherichia coil, and Streptococcus antigens in Crohn's disease , 1995, Gastroenterology.

[61]  S. Falkow,et al.  Salmonella typhimurium initiates murine infection by penetrating and destroying the specialized epithelial M cells of the Peyer's patches , 1994, The Journal of experimental medicine.

[62]  Van Kruiningen Hj,et al.  An immunocytochemical search for infectious agents in Crohn's disease. , 1993 .

[63]  H. Hahn,et al.  Involvement of M cells in the bacterial invasion of Peyer's patches: a common mechanism shared by Yersinia enterocolitica and other enteroinvasive bacteria. , 1990, Gut.

[64]  D. Laux,et al.  Colonization of the streptomycin-treated mouse large intestine by a human fecal Escherichia coli strain: role of growth in mucus , 1988, Infection and immunity.

[65]  M. Keighley,et al.  Incidence of pathogenic bacteria from mesenteric lymph nodes and ileal serosa during Crohn's disease surgery , 1984, The British journal of surgery.

[66]  E. Szigethy,et al.  Inflammatory bowel disease. , 2011, Pediatric clinics of North America.

[67]  D. Jewell,et al.  NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation , 2010, Nature Medicine.

[68]  D. Philpott,et al.  Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry , 2010, Nature Immunology.

[69]  R. Cartun,et al.  An immunocytochemical search for infectious agents in Crohn's disease. , 1993, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[70]  J. Colombel,et al.  [Bacterial translocation in Crohn disease]. , 1992, Gastroenterologie clinique et biologique.

[71]  R. Simons,et al.  Improved single and multicopy lac-based cloning vectors for protein and operon fusions. , 1987, Gene.