E. coli Pathobionts and Crohn's Disease:  Varied genetic paths leading to similar phenotypes
Crohn's disease (CD), an inflammatory bowel disease that arises from an immune attack of the GI tract, affects roughly 1.6 million Americans. The etiology of CD and the other major irritable bowel disease, ulcerative colitis, is not known, but host genetics and immunology, the gut microbiome, and environmental factors are all thought to be involved.  In addition, Adherent Invasive Escherichia coli (AIEC) strains are frequently found to be associated with CD.  Key features distinguish AIEC from commensal E. coli, including adherence/invasion of the intestinal epithelium, increased biofilm formation, increased antibiotic resistance, and survival/replication within macrophages. However, these pathobionts lack genetic features typical of frank pathogens.  Thus, the potential role AIEC play in CD pathogenesis is not clear.  The E. coli pathobiont LF82, isolated from ileum of a patient with CD, has been a well-studied, prototypic AIEC. Dozens of single nucleotide polymorphisms (SNPs) distinguish LF82 and other AIEC from commensal E. coli, suggesting that some of these genetic features might account for particular LF82 phenotypes. In this review, we summarize changes in the CD gut, the association of AIEC with CD, genes and SNPs associated with AIEC, and recent work connecting a specific SNP within a bacterial RNA polymerase gene to the expression of genes associated with the LF82 lifestyle. Overall design: To investigate the effect of a rare mutation found in the rpoB of E. coli LF82, isogenic LF82 WT and rpoB E1263A mutant were created. Gene expresion profilling analysis was performed using the data that was obtained from the RNA-seq of the isogenic pairs that were grown in triplicate. Comparative gene expression profilling analysis of the RNA-seq data for the LF82 isogenic pairs and E.coli MG1655 isogenic pairs (WT and rpoB E1263A mutant) grown at 37o C was performed Comparative gene expression profilling analysis of the RNA-seq data for the LF82 isogenic pairs (WT RNA-Seq has already been submited GEO: GSE253924, Bioproject: PRJNA1067676) grown at 37o C was performed.