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NanI Sialidase Enhances the Action of Clostridium perfringens Enterotoxin in the Presence of Mucus
Clostridium perfringens enterotoxin (CPE) is the main virulence factor for C. perfringens type F strains to cause human gastrointestinal diseases, which can involve lethal enterotoxemia. During type F disease, CPE encounters an adherent mucus layer overlying the intestines, so the current study eval...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8673254/ https://www.ncbi.nlm.nih.gov/pubmed/34908460 http://dx.doi.org/10.1128/mSphere.00848-21 |
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author | Navarro, Mauricio A. Li, Jihong Beingesser, Juliann McClane, Bruce A. Uzal, Francisco A. |
author_facet | Navarro, Mauricio A. Li, Jihong Beingesser, Juliann McClane, Bruce A. Uzal, Francisco A. |
author_sort | Navarro, Mauricio A. |
collection | PubMed |
description | Clostridium perfringens enterotoxin (CPE) is the main virulence factor for C. perfringens type F strains to cause human gastrointestinal diseases, which can involve lethal enterotoxemia. During type F disease, CPE encounters an adherent mucus layer overlying the intestines, so the current study evaluated if NanI potentiates CPE activity in the presence of adherent mucus. CPE alone caused more cytotoxicity transepithelial electrical resistance (TEER) and permeability to fluorescent dextran (FD) for minimal mucus-producing HT29 cells versus that in their derivative HT29-MTX-E12 cells, which produce abundant adherent mucus. However, for HT29-MTX-E12 cells, the presence of NanI significantly increased CPE binding and pore formation, which enhanced their sensitivity to CPE effects on cytotoxicity, TEER, and FD permeability. When the ability of NanI to potentiate CPE-induced enterotoxemia was then tested in a mouse small intestinal loop enterotoxemia model, a pathophysiologically relevant 50 μg/mL dose of CPE did not kill mice. However, the copresence of purified NanI resulted in significant CPE-induced lethality. More CPE was detected in the sera of mice challenged with 50 μg/mL of CPE when NanI was copresent during challenge. The copresence of NanI and CPE during challenge also significantly increased intestinal histologic damage compared to that after challenge with CPE alone, suggesting that NanI enhancement of CPE-induced intestinal damage may increase CPE absorption into blood. Overall, these results indicate that (i) mucus inhibits CPE action and (ii) NanI can potentiate CPE action in the presence of mucus, which may help explain why type F strains that produce relatively low levels of CPE are still pathogenic. IMPORTANCE NanI is a sialidase produced by some Clostridium perfringens type F strains. Here, we found that NanI can significantly increase the action of C. perfringens enterotoxin (CPE), which is the main toxin responsible for severe human enteric disease caused by type F strains. This effect likely helps to explain why even some type F strains that produce small amounts of CPE are pathogenic. |
format | Online Article Text |
id | pubmed-8673254 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-86732542021-12-27 NanI Sialidase Enhances the Action of Clostridium perfringens Enterotoxin in the Presence of Mucus Navarro, Mauricio A. Li, Jihong Beingesser, Juliann McClane, Bruce A. Uzal, Francisco A. mSphere Research Article Clostridium perfringens enterotoxin (CPE) is the main virulence factor for C. perfringens type F strains to cause human gastrointestinal diseases, which can involve lethal enterotoxemia. During type F disease, CPE encounters an adherent mucus layer overlying the intestines, so the current study evaluated if NanI potentiates CPE activity in the presence of adherent mucus. CPE alone caused more cytotoxicity transepithelial electrical resistance (TEER) and permeability to fluorescent dextran (FD) for minimal mucus-producing HT29 cells versus that in their derivative HT29-MTX-E12 cells, which produce abundant adherent mucus. However, for HT29-MTX-E12 cells, the presence of NanI significantly increased CPE binding and pore formation, which enhanced their sensitivity to CPE effects on cytotoxicity, TEER, and FD permeability. When the ability of NanI to potentiate CPE-induced enterotoxemia was then tested in a mouse small intestinal loop enterotoxemia model, a pathophysiologically relevant 50 μg/mL dose of CPE did not kill mice. However, the copresence of purified NanI resulted in significant CPE-induced lethality. More CPE was detected in the sera of mice challenged with 50 μg/mL of CPE when NanI was copresent during challenge. The copresence of NanI and CPE during challenge also significantly increased intestinal histologic damage compared to that after challenge with CPE alone, suggesting that NanI enhancement of CPE-induced intestinal damage may increase CPE absorption into blood. Overall, these results indicate that (i) mucus inhibits CPE action and (ii) NanI can potentiate CPE action in the presence of mucus, which may help explain why type F strains that produce relatively low levels of CPE are still pathogenic. IMPORTANCE NanI is a sialidase produced by some Clostridium perfringens type F strains. Here, we found that NanI can significantly increase the action of C. perfringens enterotoxin (CPE), which is the main toxin responsible for severe human enteric disease caused by type F strains. This effect likely helps to explain why even some type F strains that produce small amounts of CPE are pathogenic. American Society for Microbiology 2021-12-15 /pmc/articles/PMC8673254/ /pubmed/34908460 http://dx.doi.org/10.1128/mSphere.00848-21 Text en Copyright © 2021 Navarro et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Navarro, Mauricio A. Li, Jihong Beingesser, Juliann McClane, Bruce A. Uzal, Francisco A. NanI Sialidase Enhances the Action of Clostridium perfringens Enterotoxin in the Presence of Mucus |
title | NanI Sialidase Enhances the Action of Clostridium perfringens Enterotoxin in the Presence of Mucus |
title_full | NanI Sialidase Enhances the Action of Clostridium perfringens Enterotoxin in the Presence of Mucus |
title_fullStr | NanI Sialidase Enhances the Action of Clostridium perfringens Enterotoxin in the Presence of Mucus |
title_full_unstemmed | NanI Sialidase Enhances the Action of Clostridium perfringens Enterotoxin in the Presence of Mucus |
title_short | NanI Sialidase Enhances the Action of Clostridium perfringens Enterotoxin in the Presence of Mucus |
title_sort | nani sialidase enhances the action of clostridium perfringens enterotoxin in the presence of mucus |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8673254/ https://www.ncbi.nlm.nih.gov/pubmed/34908460 http://dx.doi.org/10.1128/mSphere.00848-21 |
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