Oral Presentation The 3rd Prato Conference on the Pathogenesis of Bacterial Diseases of Animals 2014

Inflammation-Associated Adherent-Invasive E. coli Are Enriched in Pathways for Use of Propanediol and Iron, and M Cell Translocation (#40)

Belgin Dogan 1 , haruo suszuki 1 , deepali Herlekar 1 , balfour Sartor 2 , Barry Campbell 2 , Carol Roberts 3 , Katrina Stewart 1 , Ellen Scherl 4 , Yasemin Araz 1 , Paulina Pavinski Bitar 1 , Tristan Lefebure 1 , Ynte Schukken 1 , Michael Stanhope 1 , Kenneth Simpson 1
  1. Cornell University, Ithaca, NY, United States
  2. Medicine, Microbiology and Immunology, UNC, Chapel Hill, NC, USA
  3. Department of Gastroenterology, University of Liverpool, Liverpool, UK
  4. Jill Roberts Center for Inflammatory Bowel Disease, Cornell University, NY, USA

Background: Perturbations of the intestinal microbiome, termed dysbiosis, are linked to intestinal inflammation. Isolation of adherent-invasive E. coli (AIEC) from intestines of Crohn’s disease (CD) patients, dogs with granulomatous colitis (GC) and mice with acute ileitis suggests these bacteria share pathoadaptive virulence factors that promote inflammation. 

Methods: To identify genes associated with AIEC, we sequenced the genomes of phylogenetically diverse AIEC strains isolated from people with CD (4), dogs with GC (2) and mice with ileitis (2) and 1 non-AIEC strain from CD ileum, and compared them to 38 genome sequences of E.coli and Shigella. We then determined the prevalence of AIEC-associated genes in 49 E.coli strains from CD patients and controls,and correlatedgenotype with invasion of intestinal epithelial cells, persistence within macrophages, AIEC pathotype, and growth in standardized conditions.

Results: Genes encoding propanediol utilization (pdu operon) and iron acquisition (yersiniabactin, chu operon) were overrepresented in AIEC relative to non-pathogenic E.coli.  PduC (propanediol dehydratase) was enriched in CD-derived AIEC, correlated with increased cellular invasion and persistence in vitro, and was increasingly expressed in fucose-containing media. Growth of AIEC required iron, and the presence of chuA (heme acquisition) correlated with persistence in macrophages. CD-associated AIEC with lpfA154(long polar fimbriae) demonstrated increased invasion of epithelial cells and translocation across M cells.

Conclusions: Our findings provide novel insights into the genetic basis of the AIEC pathotype, supporting the concept that AIEC are equipped to exploit and promote intestinal inflammation, and reveal potential targets for intervention against AIEC and inflammation associated dysbiosis.