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Annual Review of Microbiology

Volume 71, 2017

Toxin Biology

Abstract

is the cause of antibiotics-associated diarrhea and pseudomembranous colitis. The pathogen produces three protein toxins: toxins A (TcdA) and B (TcdB), and transferase toxin (CDT). The single-chain toxins TcdA and TcdB are the main virulence factors. They bind to cell membrane receptors and are internalized. The N-terminal glucosyltransferase and autoprotease domains of the toxins translocate from low-pH endosomes into the cytosol. After activation by inositol hexakisphosphate (InsP6), the autoprotease cleaves and releases the glucosyltransferase domain into the cytosol, where GTP-binding proteins of the Rho/Ras family are mono--glucosylated and, thereby, inactivated. Inactivation of Rho proteins disturbs the organization of the cytoskeleton and affects multiple Rho-dependent cellular processes, including loss of epithelial barrier functions, induction of apoptosis, and inflammation. CDT, the third toxin, is a binary actin-ADP-ribosylating toxin that causes depolymerization of actin, thereby inducing formation of the microtubule-based protrusions. Recent progress in understanding of the toxins’ actions include insights into the toxin structures, their interaction with host cells, and functional consequences of their actions.

Keyword(s): actin, ADP ribosylation, CDT, Clostridium difficile infection, Clostridium difficile toxins, Clostridium difficile transferase toxin, glucosylation, microtubules, Rho proteins, toxin receptors, toxin uptake
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2017-09-08
2025-04-21
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Clostridium difficile Toxin Biology
Annual Review of Microbiology 71, 281 (2017); https://doi.org/10.1146/annurev-micro-090816-093458
/content/journals/10.1146/annurev-micro-090816-093458
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