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

Pablo Castro-Córdova, Paola Mora-Uribe, Rodrigo Reyes-Ramírez, Glenda Cofré-Araneda, Josué Orozco-Aguilar, Christian Brito-Silva, María José Mendoza-León, Sarah A. Kuehne, Nigel P. Minton, Marjorie Pizarro-Guajardo and Daniel Paredes-Sabja ()
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Pablo Castro-Córdova: Universidad Andrés Bello
Paola Mora-Uribe: Universidad Andrés Bello
Rodrigo Reyes-Ramírez: Universidad Andrés Bello
Glenda Cofré-Araneda: Universidad Andrés Bello
Josué Orozco-Aguilar: Universidad Andrés Bello
Christian Brito-Silva: Universidad Andrés Bello
María José Mendoza-León: Universidad Andrés Bello
Sarah A. Kuehne: University of Birmingham
Nigel P. Minton: The University of Nottingham
Marjorie Pizarro-Guajardo: Universidad Andrés Bello
Daniel Paredes-Sabja: Universidad Andrés Bello

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21355-5

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