Biochem Biophys Res Commun 2015 Apr 26;459(2):259-63. Epub 2015 Feb 26.
Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, MD 21201, USA. Electronic address:
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Pathog Dis 2013 Feb 14;67(1):11-8. Epub 2013 Jan 14.
Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, MD 21201, USA
Clostridium difficile virulence requires secretion of two exotoxins: TcdA and TcdB. The precise mechanism of toxin uptake and delivery is undefined, but current models predict that the cysteine protease domain (CPD)-mediated autocleavage and release of glucosyltransferase domain (GTD) are crucial for intoxication. To determine the importance of CPD-mediated cleavage to TcdB cytotoxicity, we generated two mutant toxins--TcdB-C698S and TcdB-H653A--and assayed their abilities to intoxicate cells. Read More
Cell Mol Gastroenterol Hepatol 2018 9;5(4):611-625. Epub 2018 Feb 9.
Department of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, Maryland.
Background & Aims: toxin A (TcdA) and toxin toxin B (TcdB), the major virulence factors of the bacterium, cause intestinal tissue damage and inflammation. Although the 2 toxins are homologous and share a similar domain structure, TcdA is generally more inflammatory whereas TcdB is more cytotoxic. The functional domain of the toxins that govern the proinflammatory activities of the 2 toxins is unknown. Read More
Toxins (Basel) 2014 Jul 22;6(7):2162-76. Epub 2014 Jul 22.
Institute of Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Toxin A (TcdA) and B (TcdB) from Clostridium difficile enter host cells by receptor-mediated endocytosis. A prerequisite for proper toxin action is the intracellular release of the glucosyltransferase domain by an inherent cysteine protease, which is allosterically activated by inositol hexaphosphate (IP6). We found that in in vitro assays, the C-terminally-truncated TcdA1-1065 was more efficient at IP6-induced cleavage compared with full-length TcdA. Read More
FEBS Lett 2016 Dec 1;590(24):4550-4563. Epub 2016 Dec 1.
Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO, USA.
TcdA (308 kDa) and TcdB (270 kDa) disrupt the integrity of the intestinal epithelial barrier and provide an environment favorable for Clostridium difficile colonization. Recent evidence suggests that entry of TcdA into cells is mediated by at least two domains. Here, we report the characterization of a second receptor-binding domain (RBD2) for TcdA. Read More