Comparative genomics of Escherichia coli isolated from patients with inflammatory bowel disease

Rebecca Munk Vejborg, Viktoria Hancock, Andreas M Petersen, Karen A Krogfelt, Per Klemm, Rebecca Munk Vejborg, Viktoria Hancock, Andreas M Petersen, Karen A Krogfelt, Per Klemm

Abstract

Background: Inflammatory bowel disease (IBD) is used to describe a state of idiopathic, chronic inflammation of the gastrointestinal tract. The two main phenotypes of IBD are Crohn's disease (CD) and ulcerative colitis (UC). The major cause of IBD-associated mortality is colorectal cancer. Although both host-genetic and exogenous factors have been found to be involved, the aetiology of IBD is still not well understood. In this study we characterized thirteen Escherichia coli strains from patients with IBD by comparative genomic hybridization employing a microarray based on 31 sequenced E. coli genomes from a wide range of commensal and pathogenic isolates.

Results: The IBD isolates, obtained from patients with UC and CD, displayed remarkably heterogeneous genomic profiles with little or no evidence of group-specific determinants. No IBD-specific genes were evident when compared with the prototypic CD isolate, LF82, suggesting that the IBD-inducing effect of the strains is multifactorial. Several of the IBD isolates carried a number of extraintestinal pathogenic E. coli (ExPEC)-related virulence determinants such as the pap, sfa, cdt and hly genes. The isolates were also found to carry genes of ExPEC-associated genomic islands.

Conclusions: Combined, these data suggest that E. coli isolates obtained from UC and CD patients represents a heterogeneous population of strains, with genomic profiles that are indistinguishable to those of ExPEC isolates. Our findings indicate that IBD-induction from E. coli strains is multifactorial and that a range of gene products may be involved in triggering the disease.

Figures

Figure 1
Figure 1
Phylogenetic relationship between the isolates. Relationship based on their overall genomic profiles (left side). The Crohn's disease isolates are indicated in green and the ulcerative colitis isolates in pink. CGH data for the three phylogroup identifiers chuA, yjaA and TspE4.C (middle). Phylogenetic group association based on triplex PCR data for the same identifiers (right side).
Figure 2
Figure 2
Blast atlas comparison generated by blasting the inferred genomic sequences of the IBD isolates against the prototypic Crohn's disease isolate LF82 using the GeneWiz browser (http://www.cbs.dtu.dk/services/gwBrowser/). Blast lanes from the centre (eight CD isolates followed by five UC isolates): HM95, HM413, HM419, HM580, HM605, HM615, p29, p30, p7, p13, p19A, p19B and p22.
Figure 3
Figure 3
Comparison of the biofilm-forming capabilities of the IBD isolates and E. coli isolates obtained from IBD patients during inactive periods, and healthy control persons. Biofilm formation was monitored in LB medium using a crystal-violet, microtitre-based biofilm assay. Standard deviations are based on 3 independent experiments each comprising three replicates.
Figure 4
Figure 4
Phylogenetic relationship between the IBD isolates and a range of UTI and urosepsis isolates. The Crohn's disease isolates are indicated in green and the ulcerative colitis isolates in pink.
Figure 5
Figure 5
Blast atlas comparison generated by blasting the inferred genomic sequences of the IBD isolates against the prototypic pyelonephritis isolate CFT073 using the GeneWiz browser service. Blast lanes from the middle: HM95, HM413, HM419, HM580, HM605, HM615, p29, p30, p7, p13, p19A, p19B and p22.

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