Glucosylation Drives the Innate Inflammatory Response to Clostridium difficile Toxin A.
Infect Immun
; 84(8): 2317-2323, 2016 08.
Article
em En
| MEDLINE
| ID: mdl-27271747
ABSTRACT
Clostridium difficile is a major, life-threatening hospital-acquired pathogen that causes mild to severe colitis in infected individuals. The tissue destruction and inflammation which characterize C. difficile infection (CDI) are primarily due to the Rho-glucosylating toxins A and B. These toxins cause epithelial cell death and induce robust inflammatory signaling by activating the transcription factor NF-κB, leading to chemokine and cytokine secretion. The toxins also activate the inflammasome complex, which leads to secretion of the pyrogenic cytokine IL-1ß. In this study, we utilized glucosylation-deficient toxin A to show that activation of the inflammasome by this toxin is dependent on Rho glucosylation, confirming similar findings reported for toxin B. We also demonstrated that tissue destruction and in vivo inflammatory cytokine production are critically dependent on the enzymatic activity of toxin A, suggesting that inhibiting toxin glucosyltransferase activity may be effective in combating this refractory disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Toxinas Bacterianas
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Clostridioides difficile
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Infecções por Clostridium
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Enterotoxinas
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Imunidade Inata
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article