Biology subjects

Castro-Cordova, P.

Publications and source records attributed to Castro-Cordova, P..

3 recordsLinked to original sources

bioRxiv2021

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

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.

microbiology↗

bioRxiv2021

A ligated intestinal loop mouse model protocol to study the interactions of Clostridioides difficile spores with the intestinal mucosa during aging.

The interaction of the Clostridioides difficile spores with the intestinal mucosa contribute to the persistence and recurrence of the infection. Advanced age is one of the main risk factors to manifest C. difficile infection and recurrence. However, the interaction of C. difficile spores with the intestinal mucosa during aging has not been evaluated. In the present work, we provide a detailed protocol with all the critical information to perform an intestinal ligated loop. Using this technique in a mouse model, we evaluated C. difficile spore adherence and internalization to the ileum and colonic mucosa during aging. Consequently, our data suggest that spore internalization in the ileum and colonic mucosa is higher in elderly than in adults or young mice. Also, our data suggest that spore-adherence to the ileum and colonic mucosa decreases with aging.

microbiology↗

bioRxiv2020

Clostridioides difficile spore-entry into intestinal epithelial cells contributes to recurrence of the disease

Clostridioides difficile spores produced during infection are essential for the recurrence of the disease. However, how C. difficile spores persist in the intestinal mucosa to cause recurrent infection remains unknown. Here, we show that C. difficile spores gain entry into the intestinal mucosa via fibronectin-5{beta}1 and vitronectin-v{beta}1 specific-pathways. The spore-surface exosporium BclA3 protein is essential for both spore-entry pathways into intestinal epithelial cells. Furthermore, C. difficile spores of a bclA3 isogenic mutant exhibited reduced entry into the intestinal mucosa and reduced recurrence of the disease in a mouse model of the disease. Inhibition of C. difficile spore-entry led to reduced spore-entry into the intestinal epithelial barrier and recurrence of C. difficile infection in vivo. These findings suggest that C. difficile spore-entry into the intestinal barrier is a novel mechanism of spore-persistence that can contribute to infection recurrence and have implications for the rational design of therapies.

microbiology↗