Analysis of the σERegulon in Crohn's Disease-Associated Escherichia coli Revealed Involvement of thewaaWVLOperon in Biofilm Formation
ABSTRACTIleal lesions of patients with Crohn's disease are colonized by adherent-invasiveEscherichia coli(AIEC), which is able to adhere to and to invade intestinal epithelial cells (IEC), to replicate within macrophages, and to form biofilms on the surface of the intestinal mucosa. Previous analyses indicated the involvement of the σEpathway in AIEC-IEC interaction, as well as in biofilm formation, with σEpathway inhibition leading to an impaired ability of AIEC to colonize the intestinal mucosa and to form biofilms. The aim of this study was to characterize the σEregulon of AIEC strain LF82 in order to identify members involved in AIEC phenotypes. Using comparativein silicoanalysis of the σEregulon, we identified thewaaWVLoperon as a new member of the σEregulon in reference AIEC strain LF82. We determined that thewaaWVLoperon is involved in AIEC lipopolysaccharide structure and composition, and thewaaWVLoperon was found to be essential for AIEC strains to produce biofilm and to colonize the intestinal mucosa.IMPORTANCEAn increased prevalence of adherent-invasiveEscherichia coli(AIEC) bacteria was previously observed in the intestinal mucosa of Crohn's disease (CD) patients, and clinical observations revealed bacterial biofilms associated with the mucosa of CD patients. Here, analysis of the σEregulon in AIEC and commensalE. coliidentified 12 genes controlled by σEonly in AIEC. Among them, WaaWVL factors were found to play an essential role in biofilm formation and mucosal colonization by AIEC. In addition to identifying molecular tools that revealed a pathogenic population ofE. colicolonizing the mucosa of CD patients, these results indicate that targeting thewaaWVLoperon could be a potent therapeutic strategy to interfere with the ability of AIEC to form biofilms and to colonize the gut mucosa.