A leaky human colon model reveals uncoupled apical/basal cytotoxicity in early <i>Clostridioides difficile</i> toxin exposure
Meryem T. Ok, Jintong Liu, R. Jarrett Bliton, Caroline M. Hinesley, Ekaterina Ellyce T. San Pedro, Keith A. Breau, Ismael Gomez-Martinez, Joseph Burclaff, Scott T. Magness
Abstract
Novel human colonocyte monolayer cultures, benchmarked by transcriptomics for physiological relevance, detect early cytopathic impacts of Clostridioides difficile toxins TcdA and TcdB. A fluorescent ZO-1 reporter in primary human colonocytes is used to track epithelial barrier disruption in response to TcdA. Basal TcdA/B exposure generally caused more rapid onset and cytotoxicity than apical exposure. Transcriptomics demonstrate changes in tight junction, chemokine, and cytokine receptor gene expression post-TcdA exposure. Diclofenac-induced leaky epithelium enhanced apical exposure toxicity.