Repetitive domain of Clostridium difficile toxin B exhibits cytotoxic effects on human intestinal epithelial cells and decreases epithelial barrier function

A novel approach to generate a recombinant toxoid vaccine against Clostridium difficile

“…We observed that genetic neutralization of both mechanisms in TcdB does not completely eliminate toxicity, as residual cytotoxicity at concentrations of >10 µg ml −1 was still detected (Table 1). We speculate that the source of this remaining toxicity may be related to incomplete suppression of pore-forming activity by the double E970K/E976K mutation, or due to saturation of potentially multifunctional host-cell receptors mediating endocytosis of the TcdB protein (Zemljic et al , 2010). Nevertheless, we demonstrated that complete neutralization could be achieved when the TM mutant toxins were pre-incubated with specific antibodies.…”

Attenuation of Clostridium difficile toxin‐induced damage to epithelial barrier by ecto‐5′‐nucleotidase (CD73) and adenosine receptor signaling

“…These proteins bind to zonula occludens (ZO) family members, which in turn are anchored to the perijunctional ring. A number of reports have previously documented decreased association of actin filaments with ZO‐1, accompanied by breakdown of other tight junction protein organizations, upon exposure of intestinal epithelial cells to Cdf toxins . The loss of the tight junction integrity with Cdf toxin exposure leads to increased paracellular movement of particles across the epithelial layer …”

A chimeric protein comprising the glucosyltransferase and cysteine proteinase domains of toxin B and the receptor binding domain of toxin A induces protective immunity againstClostridium difficileinfection in mice and hamsters

“…41 In addition, trans-membrane domain of TcdB has also been reported to contribute to toxicity. 42 To ensure that mTcd138 was atoxic, 2 amino acids, which have been reported to be the key residues involved in the GT activity, 43,44 were mutated in the GT domain of TcdB (Fig.…”