In the currently prevailing model, a major role for TcdC in the repression of toxin genes has been proposed on the basis of three lines of evidence. First, in C. difficile VPI10463 (a high toxin producing strain that also expresses high levels of TcdC [18, 29] ), an inverse correlation between the transcription of tcdC and the genes encoding the toxins is found [16, 18, 29] . This correlation for TcdC is also observed in protein levels [20] . Second, elegant in vitro experiments have established that heterologously produced and purified TcdC protein can interfere with TcdR-mediated transcription of toxin genes in a way that is not yet fully understood [12] . Finally, a frame shift mutation (D117 bp) in tcdC, that results in a non-functional protein, is associated with increased toxin production in certain (hyper)virulent strains [15, 22] .