Jill Roberts Center for Inflammatory Bowel Disease

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Inflammation-associated adherent-invasive Escherichia coli are enriched in pathways for use of propanediol and iron and M-cell translocation.

TitleInflammation-associated adherent-invasive Escherichia coli are enriched in pathways for use of propanediol and iron and M-cell translocation.
Publication TypeJournal Article
Year of Publication2014
AuthorsDogan B, Suzuki H, Herlekar D, R Sartor B, Campbell BJ, Roberts CL, Stewart K, Scherl EJ, Araz Y, Bitar PP, Lef├ębure T, Chandler B, Schukken YH, Stanhope MJ, Simpson KW
JournalInflamm Bowel Dis
Volume20
Issue11
Pagination1919-32
Date Published2014 Nov
ISSN1536-4844
KeywordsAnimals, Bacterial Adhesion, Biomarkers, Case-Control Studies, Colitis, Ulcerative, Crohn Disease, DNA, Bacterial, Dogs, Dysentery, Bacillary, Escherichia coli, Escherichia coli Infections, Fimbriae, Bacterial, Gene Expression Profiling, Genome, Bacterial, Humans, Ileitis, Inflammation, Intestinal Mucosa, Iron, Macrophages, Mice, Oligonucleotide Array Sequence Analysis, Phylogeny, Propylene Glycols, Shigella, Signal Transduction, Virulence Factors
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.

DOI10.1097/MIB.0000000000000183
Alternate JournalInflamm. Bowel Dis.
PubMed ID25230163
Grant List074949/Z/04/Z / / Wellcome Trust / United Kingdom
R01 DK53347 / DK / NIDDK NIH HHS / United States