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; Daniel Paredes-Sabja

doi:10.1038/s41467-021-21355-5

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
, Daniel Paredes-Sabja^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

64 Scopus citations

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-α_vβ₁. 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.

Original language	English
Article number	1140
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-21355-5
State	Published - 1 Dec 2021
Externally published	Yes

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Publisher Copyright:
© 2021, The Author(s).

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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

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title = "Entry of spores into intestinal epithelial cells contributes to recurrence of Clostridioides difficile infection",

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.",

author = "Pablo Castro-C{\'o}rdova and Paola Mora-Uribe and Rodrigo Reyes-Ram{\'i}rez and Glenda Cofr{\'e}-Araneda and Josu{\'e} Orozco-Aguilar and Christian Brito-Silva and Mendoza-Le{\'o}n, \{Mar{\'i}a Jos{\'e}\} and Kuehne, \{Sarah A.\} and Minton, \{Nigel P.\} and Marjorie Pizarro-Guajardo and Daniel Paredes-Sabja",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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doi = "10.1038/s41467-021-21355-5",

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Castro-Córdova, P, Mora-Uribe, P, Reyes-Ramírez, R, Cofré-Araneda, G, Orozco-Aguilar, J, Brito-Silva, C, Mendoza-León, MJ, Kuehne, SA, Minton, NP, Pizarro-Guajardo, M & Paredes-Sabja, D 2021, 'Entry of spores into intestinal epithelial cells contributes to recurrence of Clostridioides difficile infection', Nature Communications, vol. 12, no. 1, 1140. https://doi.org/10.1038/s41467-021-21355-5

TY - JOUR

T1 - Entry of spores into intestinal epithelial cells contributes to recurrence of Clostridioides difficile infection

AU - Castro-Córdova, Pablo

AU - Mora-Uribe, Paola

AU - Reyes-Ramírez, Rodrigo

AU - Cofré-Araneda, Glenda

AU - Orozco-Aguilar, Josué

AU - Brito-Silva, Christian

AU - Mendoza-León, María José

AU - Kuehne, Sarah A.

AU - Minton, Nigel P.

AU - Pizarro-Guajardo, Marjorie

AU - Paredes-Sabja, Daniel

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85101212081

U2 - 10.1038/s41467-021-21355-5

DO - 10.1038/s41467-021-21355-5

M3 - Article

C2 - 33602902

AN - SCOPUS:85101212081

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1140

ER -

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

Abstract

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