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bioRxiv · 10.1101/2021.09.01.458577

E-cadherin redistribution mediated by Clostridioides difficile toxins increases spore-association to adherens junctions

Castro-Cordova, P.·Otto-Medina, M.·Lacy, B.·Paredes-Sabja, D.
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Abstract

Clostridioides difficile causes antibiotic-associated diseases in humans ranging from mild diarrhea to severe pseudomembranous colitis and death. A major clinical challenge is the prevention of disease recurrence, which affects nearly [~]20 - 30 % of the patients with a primary C. difficile infection (CDI). During CDI, C. difficile forms metabolically dormant spores that are essential for recurrence of CDI (R-CDI). In prior studies, we have shown that C. difficile spores interact with intestinal epithelial cells (IECs), which contributes to R-CDI. However, this interaction remains poorly understood. Here, we provide evidence that C. difficile spores interact with E-cadherin, contributing to spore-adherence and internalization into IECs. C. difficile toxins TcdA/TcdB lead to adherens junctions opening and increase spore-adherence to IECs. Confocal micrographs demonstrate that C. difficile spores associate with accessible E-cadherin; spore-E-cadherin association increases upon TcdA/TcdB intoxication. The presence of anti-E-cadherin antibodies decreased spore adherence and entry into IECs. By ELISA, immunofluorescence, and immunogold labelling, we observed that E-cadherin binds to C. difficile spores, specifically to the hair-like projections of the spore, reducing spore-adherence to IECs. Overall, these results expand our knowledge of how C. difficile spores bind to IECs by providing evidence that E-cadherin acts as a spore-adherence receptor to IECs and by revealing how toxin-mediated damage affects spore interactions with IECs.

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Castro-Cordova, P., Otto-Medina, M., Lacy, B., Paredes-Sabja, D.. 2021-09-01. E-cadherin redistribution mediated by Clostridioides difficile toxins increases spore-association to adherens junctions. https://doi.org/10.1101/2021.09.01.458577

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