Nectin-3 and shed forms of CSPG4 can serve as epithelial cell receptors for Clostridioides difficile TcdB

Toxin B (TcdB) is a major virulence factor of , a Gram-positive pathogen that is a leading cause of hospital-acquired diarrhea. While previous studies have established that TcdB can engage multiple cell surface receptors , little is known about how these interactions promote disease and where these...

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Bibliographic Details
Published in:mBio 2023-10, Vol.14 (5), p.e0185723
Main Authors: Childress, Kevin O, Cencer, Caroline S, Tyska, Matthew J, Lacy, D Borden
Format: Article
Language:English
Subjects:
Clostridium difficile
Host-Microbial Interactions
polarized epithelia
Research Article
toxin-receptor interaction
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Summary:Toxin B (TcdB) is a major virulence factor of , a Gram-positive pathogen that is a leading cause of hospital-acquired diarrhea. While previous studies have established that TcdB can engage multiple cell surface receptors , little is known about how these interactions promote disease and where these receptors localize on colonic tissue. Here, we used immunofluorescence microscopy to visualize Nectin-3 and CSPG4 on tissue, revealing unexpected localization of both receptors on colonic epithelial cells. We show that Nectin-3, which was previously characterized as an adherens junction protein, is also localized to the brush border of colonocytes. Staining for CSPG4 revealed that it is present along epithelial cell junctions, suggesting that it is shed by fibroblasts along the crypt-surface axis. Collectively, our study provides new insights into how TcdB can gain access to the receptors Nectin-3 and CSPG4 to intoxicate colonic epithelial cells.
ISSN:2150-7511
2150-7511
DOI:10.1128/mbio.01857-23