Crohn's Disease Pathobiont Adherent-Invasive E coli Disrupts Epithelial Mitochondrial Networks With Implications for Gut Permeability.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32992049", "kind": "science-record", "revision": 8, "content_hash": "sha256:6c5c17d0a987f4d0c612f6a7321dd395e82a2d2d0bf6eddb523474fee2571231", "created_at": "2026-11-01T15:41:11Z", "updated_at": "2026-11-01T22:45:23Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Crohn's Disease Pathobiont Adherent-Invasive E coli Disrupts Epithelial Mitochondrial Networks With Implications for Gut Permeability.", "doi": "10.1016/j.jcmgh.2020.09.013", "pmid": "32992049", "authors": ["Nicole L Mancini", "Sruthi Rajeev", "Timothy S Jayme", "Arthur Wang", "Åsa V Keita", "Matthew L Workentine", "Samira Hamed", "Johan D Söderholm", "Fernando Lopes", "Timothy E Shutt", "Jane Shearer", "Derek M McKay"], "journal": "Cellular and molecular gastroenterology and hepatology", "year": 2021, "abstract": "BACKGROUND & AIMS: Adherent-invasive Escherichia coli are implicated in inflammatory bowel disease, and mitochondrial dysfunction has been observed in biopsy specimens from patients with inflammatory bowel disease. As a novel aspect of adherent-invasive E coli-epithelial interaction, we hypothesized that E coli (strain LF82) would elicit substantial disruption of epithelial mitochondrial form and function.\nMETHODS: Monolayers of human colon-derived epithelial cell lines were exposed to E coli-LF82 or commensal E coli and RNA sequence analysis, mitochondrial function (adenosine triphosphate synthesis) and dynamics (mitochondrial network imaging, immunoblotting for fission and fusion proteins), and epithelial permeability (transepithelial resistance, flux of fluorescein isothiocyanate-dextran and bacteria) were assessed.\nRESULTS: E coli-LF82 significantly affected epithelial expression of ∼8600 genes, many relating to mitochondrial function. E coli-LF82-infected epithelia showed swollen mitochondria, reduced mitochondrial membrane potential and adenosine triphosphate, and fragmentation of the mitochondrial network: events not observed with dead E coli-LF82, medium from bacterial cultures, or control E coli. Treatment with Mitochondrial Division Inhibitor 1 (Mdivi1, inhibits dynamin-related peptide 1, guanosine triphosphatase principally responsible for mitochondrial fission) or P110 (prevents dynamin-related peptide 1 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, which mediates mitochondrial fusion. Mitochondrial Division Inhibitor 1 reduced the magnitude of E coli-LF82-induced increased transepithelial flux of fluorescein isothiocyanate dextran. By 8 hours after infection, increased cytosolic cytochrome C and DNA fragmentation were apparent without evidence of caspase-3 or apoptosis inducing factor activation.\nCONCLUSIONS: 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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