A single rare σ70 variant establishes a unique gene expression pattern in the E. coli pathobiont LF82

Area of Science:

• Microbiology
• Genetics
• Molecular Biology

Background:

• Adherent-invasive Escherichia coli (AIEC) pathobionts are linked to Crohn's disease, but genetic factors driving their distinct phenotypes remain unclear.
• Understanding the genetic basis of AIEC pathobiont emergence is crucial for elucidating Crohn's disease etiology.

Purpose of the Study:

• To identify genetic variations distinguishing AIEC pathobionts from other E. coli strains.
• To investigate the functional impact of a specific single nucleotide polymorphism (SNP) in the rpoD gene of LF82.

Main Methods:

• RNA sequencing (RNA-seq) to analyze transcriptomic changes.
• In vitro transcription assays to assess promoter activity.
• Comparative analysis of LF82 and E. coli K-12 MG1655 strains.

Main Results:

• A rare SNP (D445V) in the rpoD gene of LF82 was identified.
• This SNP leads to increased antibiotic resistance, biofilm formation, and methionine biosynthesis.
• The D445V variant directly enhances transcription of specific genes, influenced by promoter elements.

Conclusions:

• The rpoD D445V SNP is a distinguishing genetic feature of the LF82 AIEC pathobiont.
• This SNP provides a novel mechanism for pathobiont emergence and adaptation.
• Findings suggest an underappreciated role of specific genetic variants in inflammatory bowel disease pathogenesis.