Adherent-invasive E. coli (AIEC) are implicated in inflammatory bowel disease (IBD), and mitochondrial dysfunction has been observed in IBD-patient biopsies. As a novel aspect of AIEC-epithelial interaction we hypothesized that E. coli (strain LF82) would elicit substantial disruption of epithelial mitochondrial form and function.
Monolayers of human colon-derived epithelial cell lines were exposed to E. coli-LF82 or commensal E. coli and RNA-sequence analysis, mitochondrial function (ATP synthesis) and dynamics (mitochondrial network imaging, immunoblotting for fission and fusion proteins), and epithelial permeability (transepithelial resistance, flux of FITC-dextran and bacteria) were assessed.
E. coli-LF82 significantly affected epithelial expression of ∼8600 genes, many relating to mitochondrial function. E. coli-LF82-infected epithelia displayed swollen mitochondria, reduced mitochondrial membrane potential and ATP, and fragmentation of the mitochondrial network: events not observed with dead E. coli-LF82, medium from bacterial cultures, or control E. coli. Treatment with Mdivi1 (inhibits dynamin-related peptide 1 (Drp1), GTPase principally responsible for mitochondrial fission) or P110 (prevents Drp1 binding to mitochondrial fission 1 protein) partially reduced E. coli-LF82-induced mitochondrial fragmentation in the short-term. E. coli-LF82-infected epithelia showed loss of the long isoform of optic atrophy factor 1 (OPA1-L), which mediates mitochondrial fusion. Mdivi1 reduced the magnitude of E. coli-LF82 induced increased transepithelial flux of FITC-dextran. By 8h post-infection, increased cytosolic cytochrome C and DNA fragmentation were apparent without evidence of caspase-3 or apoptosis inducing factor (AIF) activation.
Epithelial mitochondrial fragmentation caused by E. coli-LF82 could be targeted to maintain cellular homeostasis and mitigate infection-induced loss of epithelial barrier function.

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