title: Inflammation-associated adherent-invasive Escherichia coli are enriched in pathways for use of propanediol and iron and M-cell translocation.
abstract: BACKGROUND
  Perturbations of the intestinal microbiome, termed dysbiosis, are linked to intestinal inflammation. Isolation of adherent-invasive Escherichia coli (AIEC) from intestines of patients with Crohn's disease (CD), dogs with granulomatous colitis, 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 granulomatous colitis (2), and mice with ileitis (2) and 1 non-AIEC strain from CD ileum and compared them with 38 genome sequences of E. coli and Shigella. We then determined the prevalence of AIEC-associated genes in 49 E. coli strains from patients with CD and controls and correlated genotype 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 nonpathogenic 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 lpfA 154 (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.
authors.affiliation: Departments of *Clinical Sciences, and †Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York; ‡Department of Environmental Science and Engineering, Graduate School of Science and Engineering, Yamaguchi University, Yamaguchi, Japan; §Departments of Medicine, and ‖Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina; ¶Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; and **Department of Medicine, Jill Roberts Center for Inflammatory Bowel Disease, Weill Medical College of Cornell University, New York, New York. Dr. T. Lefébure is now with the Université de Lyon and Université Lyon 1, Centre National de la Recherche Scientifique, Ecologie des Hydrosystèmes Naturels et Anthropisés, Villeurbanne, France.
authors.forename: Belgin
authors.initials: B
authors.lastname: Dogan
authors.forename: Haruo
authors.initials: H
authors.lastname: Suzuki
authors.forename: Deepali
authors.initials: D
authors.lastname: Herlekar
authors.forename: R Balfour
authors.initials: RB
authors.lastname: Sartor
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Campbell
authors.forename: Carol L
authors.initials: CL
authors.lastname: Roberts
authors.forename: Katrina
authors.initials: K
authors.lastname: Stewart
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Scherl
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Araz
authors.forename: Paulina P
authors.initials: PP
authors.lastname: Bitar
authors.forename: Tristan
authors.initials: T
authors.lastname: Lefébure
authors.forename: Brendan
authors.initials: B
authors.lastname: Chandler
authors.forename: Ynte H
authors.initials: YH
authors.lastname: Schukken
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Stanhope
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Simpson
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D003424:Crohn Disease / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D004269:DNA, Bacterial / Q000235:genetics; D004285:Dogs; D004405:Dysentery, Bacillary / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004926:Escherichia coli / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D010861:Fimbriae, Bacterial; D020869:Gene Expression Profiling; D016680:Genome, Bacterial; D006801:Humans; D007079:Ileitis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D011409:Propylene Glycols / Q000378:metabolism*; D012760:Shigella / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D015398:Signal Transduction; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D004269:DNA, Bacterial; D011409:Propylene Glycols; D037521:Virulence Factors; C041787:1,3-propanediol; D007501:Iron