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The Relative Role of Toxins A and B in the Virulence of Clotridioides difficile

Most pathogenic strains of C. difficile possess two large molecular weight single unit toxins with four similar functional domains. The toxins disrupt the actin cytoskeleton of intestinal epithelial cells leading to loss of tight junctions, which ultimately manifests as diarrhea in the host. While i...

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Autores principales: Skinner, Andrew M., Phillips, S. Tyler, Merrigan, Michelle M., O’Leary, Kevin J., Sambol, Susan P., Siddiqui, Farida, Peterson, Lance R., Gerding, Dale N., Johnson, Stuart
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796042/
https://www.ncbi.nlm.nih.gov/pubmed/33396595
http://dx.doi.org/10.3390/jcm10010096
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author Skinner, Andrew M.
Phillips, S. Tyler
Merrigan, Michelle M.
O’Leary, Kevin J.
Sambol, Susan P.
Siddiqui, Farida
Peterson, Lance R.
Gerding, Dale N.
Johnson, Stuart
author_facet Skinner, Andrew M.
Phillips, S. Tyler
Merrigan, Michelle M.
O’Leary, Kevin J.
Sambol, Susan P.
Siddiqui, Farida
Peterson, Lance R.
Gerding, Dale N.
Johnson, Stuart
author_sort Skinner, Andrew M.
collection PubMed
description Most pathogenic strains of C. difficile possess two large molecular weight single unit toxins with four similar functional domains. The toxins disrupt the actin cytoskeleton of intestinal epithelial cells leading to loss of tight junctions, which ultimately manifests as diarrhea in the host. While initial studies of purified toxins in animal models pointed to toxin A (TcdA) as the main virulence factor, animal studies using isogenic mutants demonstrated that toxin B (TcdB) alone was sufficient to cause disease. In addition, the natural occurrence of TcdA−/TcdB+ (TcdA−/B+)mutant strains was shown to be responsible for cases of C. difficile infection (CDI) with symptoms identical to CDI caused by fully toxigenic (A+/B+) strains. Identification of these cases was delayed during the period when clinical laboratories were using immunoassays that only detected TcdA (toxA EIA). Our hospital laboratory at the time performed culture as well as toxA EIA on patient stool samples. A total of 1.6% (23/1436) of all clinical isolates recovered over a 2.5-year period were TcdA−/B+ variants, the majority of which belonged to the restriction endonuclease analysis (REA) group CF and toxinotype VIII. Despite reports of serious disease due to TcdA−/B+ CF strains, these infections were typically mild, often not requiring specific treatment. While TcdB alone may be sufficient to cause disease, clinical evidence suggests that both toxins have a role in disease.
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spelling pubmed-77960422021-01-10 The Relative Role of Toxins A and B in the Virulence of Clotridioides difficile Skinner, Andrew M. Phillips, S. Tyler Merrigan, Michelle M. O’Leary, Kevin J. Sambol, Susan P. Siddiqui, Farida Peterson, Lance R. Gerding, Dale N. Johnson, Stuart J Clin Med Article Most pathogenic strains of C. difficile possess two large molecular weight single unit toxins with four similar functional domains. The toxins disrupt the actin cytoskeleton of intestinal epithelial cells leading to loss of tight junctions, which ultimately manifests as diarrhea in the host. While initial studies of purified toxins in animal models pointed to toxin A (TcdA) as the main virulence factor, animal studies using isogenic mutants demonstrated that toxin B (TcdB) alone was sufficient to cause disease. In addition, the natural occurrence of TcdA−/TcdB+ (TcdA−/B+)mutant strains was shown to be responsible for cases of C. difficile infection (CDI) with symptoms identical to CDI caused by fully toxigenic (A+/B+) strains. Identification of these cases was delayed during the period when clinical laboratories were using immunoassays that only detected TcdA (toxA EIA). Our hospital laboratory at the time performed culture as well as toxA EIA on patient stool samples. A total of 1.6% (23/1436) of all clinical isolates recovered over a 2.5-year period were TcdA−/B+ variants, the majority of which belonged to the restriction endonuclease analysis (REA) group CF and toxinotype VIII. Despite reports of serious disease due to TcdA−/B+ CF strains, these infections were typically mild, often not requiring specific treatment. While TcdB alone may be sufficient to cause disease, clinical evidence suggests that both toxins have a role in disease. MDPI 2020-12-30 /pmc/articles/PMC7796042/ /pubmed/33396595 http://dx.doi.org/10.3390/jcm10010096 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Skinner, Andrew M.
Phillips, S. Tyler
Merrigan, Michelle M.
O’Leary, Kevin J.
Sambol, Susan P.
Siddiqui, Farida
Peterson, Lance R.
Gerding, Dale N.
Johnson, Stuart
The Relative Role of Toxins A and B in the Virulence of Clotridioides difficile
title The Relative Role of Toxins A and B in the Virulence of Clotridioides difficile
title_full The Relative Role of Toxins A and B in the Virulence of Clotridioides difficile
title_fullStr The Relative Role of Toxins A and B in the Virulence of Clotridioides difficile
title_full_unstemmed The Relative Role of Toxins A and B in the Virulence of Clotridioides difficile
title_short The Relative Role of Toxins A and B in the Virulence of Clotridioides difficile
title_sort relative role of toxins a and b in the virulence of clotridioides difficile
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796042/
https://www.ncbi.nlm.nih.gov/pubmed/33396595
http://dx.doi.org/10.3390/jcm10010096
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