Abstract
Adherent-invasive Escherichia coli (AIEC) have been involved in Crohn’s disease (CD). Currently, AIEC are identified by time-consuming techniques based on in vitro infection of cell lines to determine their ability to adhere to and invade intestinal epithelial cells as well as to survive and replicate within macrophages. Our aim was to find signature sequences that can be used to identify the AIEC pathotype. Comparative genomics was performed between three E. coli strain pairs, each pair comprised one AIEC and one non-AIEC with identical pulsotype, sequence type and virulence gene carriage. Genetic differences were further analysed in 22 AIEC and 28 non-AIEC isolated from CD patients and controls. The strain pairs showed similar genome structures, and no gene was specific to AIEC. Three single nucleotide polymorphisms displayed different nucleotide distributions between AIEC and non-AIEC, and four correlated with increased adhesion and/or invasion indices. Here, we present a classification algorithm based on the identification of three allelic variants that can predict the AIEC phenotype with 84% accuracy. Our study corroborates the absence of an AIEC-specific genetic marker distributed across all AIEC strains. Nonetheless, point mutations putatively involved in the AIEC phenotype can be used for the molecular identification of the AIEC pathotype.
Highlights
Crohn’s disease (CD) is an idiopathic chronic inflammatory bowel disease (IBD) involving host genetics, environmental factors and the intestinal microbiome[1]
Desphande et al.[30] described 29 diagnostic single-nucleotide polymorphisms (SNPs) that cause either synonymous or non-synonymous amino acid changes as a signature sequence that differentiates a group of B2-pathogenic strains comprising 4 Adherent-invasive Escherichia coli (AIEC), 3 extraintestinal pathogenic E. coli (ExPEC), 47 uropathogenic E. coli and 1 avian pathogenic E. coli strains from other E. coli strains present in the NCBI database
The AIEC pathotype is of interest due to its association with gut inflammation in CD patients[2,3,4,7,8,9,10]
Summary
Crohn’s disease (CD) is an idiopathic chronic inflammatory bowel disease (IBD) involving host genetics, environmental factors and the intestinal microbiome[1]. Genomic studies have confirmed that AIEC resemble ExPEC17,24,30 These studies have been useful in the detection of virulence genes that are enriched in CD-isolated AIEC strains relative to those in non-IBD-isolated AIEC strains. By comparing AIEC and non-AIEC strains of the same phylogroup, Desilets et al.[24] found three genomic regions present in all B2-phylogroup AIEC strains and absent from AIEC strains of other phylogroups and commensal strains of any phylogenetic origin (including B2) Whether these regions are specific to B2-AIEC strains only or present in other pathogenic groups that share the same phylogenetic origin, such as B2 ExPEC strains is unknown. O’Brien et al.[27] reduced gene content variability by conducting genomic analysis of a set of B2-phylogroup E. coli strains with identical sequence type (ST95), thereby decreasing the likelihood of detecting differential genetic elements delimited by the phylogenetic background. The evaluation of gene prevalence and base composition of core genes did not result in the identification of an AIEC-specific biomarker or even in the identification of a marker common to most of the AIEC strains examined in that study
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