Comparative genomics of clonally identical Adherent Invasive Escherichia coli (AIEC) and non-AIEC pairs for the identification of genetic determinants associated with the AIEC phenotype

Recent studies have implicated the pathovar adherent-invasive Escherichia coli (AIEC) in the etiology of Crohn's disease, particularly in patients with ileal involvement. The AIEC patovar is defined by its ability to adhere to and to invade intestinal epithelial cells and by the capacity to survive and to replicate within macrophages. To date, the AIEC strains isolated are genetically diverse, belong to different phylogroups and can carry several groups of virulence genes characteristic of extraintestinal pathogenic E. coli. However, the virulence genes found so far do not explain the AIEC phenotype. On the other hand, genes relevant to the pathovar pathogenicity have also been found in non-pathogenic E. coli strains. Taken all together, the genetic determinants responsible for the AIEC phenotype remain to be elucidated.E. coli isolates sharing identical macrorestriction patterns differ in their adherent-invasive phenotype, suggesting that AIEC may arise from point mutations or differential gene expression of core genes. Therefore, comparative genomics of E. coli strain pairs consisting on two isolates with the same pulsed field gel electrophoresis fingerprint but that differ in their adherent-invasive phenotype may help in identifying AIEC associated genes. In this project we aimed to identify genetic elements specific for the AIEC pathotype and to decipher the mechanism by which the genetic elements are involved in AIEC pathogenicity. Three pairs of strains belonging to B2, D and B1 phylogroups were sequenced in order to determine the genetic differences between strain-pairs AIEC /non-AIEC and to determine genes shared among AIEC from different phylogroups.Obtaining molecular tools specific for the AIEC pathotype are of great relevance as the current available techniques to identify this pathotype are based exclusively in phenotypic screening of cultured bacteria. Moreover, identifying the genetic elements associated with the AIEC phenotype may help in better understanding the mechanisms of pathogenicity of the pathotype and also could imply a significant advance in the detection of new therapeutic targets for Crohn's disease.