Redistribution of the Novel Clostridioides difficile Spore Adherence Receptor E-Cadherin by TcdA and TcdB Increases Spore Binding to Adherens Junctions
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Archivos
Fecha
2023
Profesor/a Guía
Facultad/escuela
Idioma
en_US
Título de la revista
ISSN de la revista
Título del volumen
Editor
Infection and Immunity, Volume 91, Issue 1 January 2023
Nombre de Curso
Licencia CC
Attribution 4.0 International
CC BY 4.0
Deed
Licencia CC
https://creativecommons.org/licenses/by/4.0/
Resumen
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 to 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 contribute 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 and 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 and TcdB intoxication. The presence of anti-E-cadherin antibodies decreased spore adherence and entry into IECs. By enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and immunogold labeling, we observed that E-cadherin binds to C. difficile spores, specifically to the hairlike 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. Copyright © 2022 American Society for Microbiology. All Rights Reserved
Notas
Indexación: Scopus
Palabras clave
Adherens Junctions, Bacterial Proteins, Bacterial Toxins, Clostridioides, Clostridioides difficile, Humans, Spores, Bacterial, bacterial toxin, blocking antibody, tcda protein, tcdb protein, unclassified drug, uvomorulin, bacterial protein, bacterial toxin
Citación
DOI
10.1128/iai.00476-22