Entry of spores into intestinal epithelial cells contributes to recurrence of Clostridioides difficile infection

Castro-Córdova, Pablo; Mora-Uribe, Paola; Reyes-Ramírez, Rodrigo; Cofré-Araneda, Glenda; Orozco-Aguilar, Josué; Brito-Silva, Christian; Mendoza-León, María José; Kuehne, Sarah A.; Minton, Nigel P.; Pizarro-Guajardo, Marjorie; Paredes-Sabja, Daniel

Abstract

Clostridioides difficile spores produced during infection are important for the recurrence of the disease. Here, we show that C. difficile spores gain entry into the intestinal mucosa via pathways dependent on host fibronectin-α5β1 and vitronectin-αvβ1. The exosporium protein BclA3, on the spore surface, is required for both entry pathways. Deletion of the bclA3 gene in C. difficile, or pharmacological inhibition of endocytosis using nystatin, leads to reduced entry into the intestinal mucosa and reduced recurrence of the disease in a mouse model. Our findings indicate that C. difficile spore entry into the intestinal barrier can contribute to spore persistence and infection recurrence, and suggest potential avenues for new therapies.

Citation

Castro-Córdova, P., Mora-Uribe, P., Reyes-Ramírez, R., Cofré-Araneda, G., Orozco-Aguilar, J., Brito-Silva, C., Mendoza-León, M. J., Kuehne, S. A., Minton, N. P., Pizarro-Guajardo, M., & Paredes-Sabja, D. (2021). Entry of spores into intestinal epithelial cells contributes to recurrence of Clostridioides difficile infection. Nature Communications, 12(1), Article 1140. https://doi.org/10.1038/s41467-021-21355-5

• Journal Article Type: Article
• Acceptance Date: Jan 19, 2021
• Online Publication Date: Feb 18, 2021
• Publication Date: 2021-12
• Deposit Date: Jun 20, 2025
• Publicly Available Date: Jun 20, 2025
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 1
• Article Number: 1140
• DOI: https://doi.org/10.1038/s41467-021-21355-5
• Keywords: General Biochemistry, Genetics and Molecular Biology; General Physics and Astronomy; General Chemistry
• Public URL: https://nottingham-repository.worktribe.com/output/5353167
• Publisher URL: https://www.nature.com/articles/s41467-021-21355-5#
• Additional Information: Received: 11 February 2020; Accepted: 19 January 2021; First Online: 18 February 2021; : D.P.-S. and P.C.-C. are inventors on the PCT WO2020035720 (A1) patent relating to a method and pharmacological composition for the prevention of recurrent infections caused by Clostridioides difficile, submitted by Universidad Andrés Bello. The other authors declare no competing interests.