The large clostridial toxins (LCTs) are an important group of bacterial virulence factors, produced by C. difficile, C. sordellii, C. perfringens and C. novyi. In C. difficile, the LCTs are encoded within a pathogenicity locus known as PaLoc, which also encodes an alternative sigma factor, known as TcdR, which is essential for LCT production. It has been suggested that a similar mechanism might also be employed in the other clostridia to control LCT expression. This is supported by the recent identification of a TcdR-family protein in C. sordellii, known as TcsR, which is encoded within a PaLoc-like region and is essential for LCT production. Despite these recent advances, with the exception of C. difficile little is known regarding the environmental cues or regulatory cascades that control LCT production.
In this study we show for the first time that the production of LCTs in C. sordellii and C. perfringens is subject to temporal regulation and is repressed by glucose in a similar manner to LCT production in C. difficile. Furthermore, we have identified a previously uncharacterised PaLoc-like region in C. perfringens, encoding the LCT, TpeL, along with two accessory genes predicted to encode a holin-type protein, and a TcdR-family protein, named TpeR. Inactivation of the tpeR gene demonstrated that TpeR plays a critical role in controlling TpeL production in C. perfringens. Finally, despite its similarities to the TcdR-family of alternative sigma factors, cross-complementation studies show that TpeR is not functionally interchangeable with TcdR or TcsR from C. difficile and C. sordellii, respectively. These data therefore suggest that important differences may exist between the members of the TcdR-family of clostridial toxin regulators.