Comparative genomics of Crohn's disease-associated adherent, invasive E. coli

Objective Adherent-invasive E. coli (AIEC) are a leading candidate bacterial trigger for Crohn’s disease (CD). The AIEC pathovar is defined by in vitro cell-line assays examining specific bacteria/cell interactions. No molecular marker exists for their identification. Our aim was to identify a molecular property common to the AIEC phenotype. Design 41 B2 phylogroup E. coli strains were isolated from 36 Australian subjects: 19 patients with inflammatory bowel disease (IBD) and 17 without. Adherence/invasion assays were conducted using the I-407 epithelial cell line and survival/replication assays using the THP-1 macrophage cell line. Cytokine secretion (TNF-α, IL-6, IL-8, and IL-10) was measured using ELISA. The genomes were assembled and annotated, and cluster analysis performed using CD-HIT. The resulting matrices were analysed to identify genes unique/more frequent in AIEC strains compared to non-AIEC strains. Base composition differences and CRISPR analyses were conducted. Results Of all B2 phylogroup strains assessed, 79% could survive and replicate in macrophages. Among them, 11/41 strains (5 CD, 2 ulcerative colitis, 5 non-IBD) also adhere to and invade epithelial cells, a phenotype assigning them to the AIEC pathovar. The AIEC strains were phylogenetically heterogeneous. We did not identify a gene (or nucleic acid base composition differences) common to all, or the majority of, AIEC. Cytokine secretion and CRISPRs were not associated with the AIEC phenotype. Conclusions Comparative genomic analysis of AIEC and non-AIEC strains did not identify a molecular property exclusive to the AIEC phenotype. We recommend a broader approach to the identification of the bacteria-host interactions that are important in the pathogenesis of Crohn’s disease.
Type
Collection
Title
Comparative genomics of Crohn's disease-associated adherent, invasive E. coli
Brief Title
Genomics of adherent, invasive E. coli
Collection Type
Repository
Access Privileges
Research School of Biology
DOI - Digital Object Identifier
10.4225/13/56F08C5B5F0FE
Metadata Language
English
Data Language
English
Significance Statement
This study represents the most comprehensive genome comparison of adherent, invasive Escherichia coli strains to-date.
Brief Description
Adherent invasive E. coli (AIEC) and non-AIEC genomes were compared.
Full Description
Objective Adherent-invasive E. coli (AIEC) are a leading candidate bacterial trigger for Crohn’s disease (CD). The AIEC pathovar is defined by in vitro cell-line assays examining specific bacteria/cell interactions. No molecular marker exists for their identification. Our aim was to identify a molecular property common to the AIEC phenotype. Design 41 B2 phylogroup E. coli strains were isolated from 36 Australian subjects: 19 patients with inflammatory bowel disease (IBD) and 17 without. Adherence/invasion assays were conducted using the I-407 epithelial cell line and survival/replication assays using the THP-1 macrophage cell line. Cytokine secretion (TNF-α, IL-6, IL-8, and IL-10) was measured using ELISA. The genomes were assembled and annotated, and cluster analysis performed using CD-HIT. The resulting matrices were analysed to identify genes unique/more frequent in AIEC strains compared to non-AIEC strains. Base composition differences and CRISPR analyses were conducted. Results Of all B2 phylogroup strains assessed, 79% could survive and replicate in macrophages. Among them, 11/41 strains (5 CD, 2 ulcerative colitis, 5 non-IBD) also adhere to and invade epithelial cells, a phenotype assigning them to the AIEC pathovar. The AIEC strains were phylogenetically heterogeneous. We did not identify a gene (or nucleic acid base composition differences) common to all, or the majority of, AIEC. Cytokine secretion and CRISPRs were not associated with the AIEC phenotype. Conclusions Comparative genomic analysis of AIEC and non-AIEC strains did not identify a molecular property exclusive to the AIEC phenotype. We recommend a broader approach to the identification of the bacteria-host interactions that are important in the pathogenesis of Crohn’s disease.
Contact Email
claire.obrien@anu.edu.au; clairelouiseobrien@icloud.com
Contact Address
Lvl 5, Bldg 10, Canberra Hospital Yamba Drive, Garran ACT 2605
Contact Phone Number
0406687565
Principal Investigator
Dr Claire O'Brien
Fields of Research
110899 - Medical Microbiology not elsewhere classified; 119999 - Medical and Health Sciences not elsewhere classified
Keywords
Crohn's disease; Genome, Microbial; Escherichia coli; Microbiology
Date Coverage
2016
2027
Date of data creation
2015
Year of data publication
2016
Creator(s) for Citation
Claire
O'Brien
Publisher for Citation
Gut
Access Rights
Contact Chief Investigator if you wish to use the data. Cite the relevant publication.
Embargo Date
2016-01-01
Retention Period
10 years
Disposal Date
2026
Extent or Quantity
42
Data Size
404 MB
Status: Published
Published to:
  • Australian National University
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