CdtR (only) the regulator of binary toxin in Clostridium difficile

Bilverstone, T. W.; Kinsmore, N. L.; Minton, N. P. and Kuehne, S. A. (2016). CdtR (only) the regulator of binary toxin in Clostridium difficile. In: The 13th Biennial Congress of the Anaerobe Society of the Americas, 11-14 Jul 2016, Tennessee, USA..


Clostridium difficile is a Gram-positive, endospore forming, anaerobic bacterium, responsible for most hospital acquired antibiotic induced diarrhoeal disease. The spores act as mean of transmission, while the disease itself is toxin mediated. Most strains produce two large glycosylating toxins, named toxin A and B, but about 20% of clinical isolates produce an additional binary toxin, called C. difficile toxin (CDT). CDT has been implicated in more severe infections and also in relapse, but little is known about its actual contribution to pathogenesis and disease outcome. Some evidence has been obtained that CDT might play a role in colonisation and there is also further data suggesting that it might act in concert with the large toxins. It is thought to be regulated by a LytTR response regulator, CdtR, encoded just upstream. Interestingly most strains that do not carry functional CDT genes have a ghost locus, encoding an intact copy of cdtR, but truncated cdt genes. Very few strains do not have cdtR; instead, these carry a conserved 68bp fragment.

Here we are exploring the following two research questions: Is CdtR absolutely required for functional binary toxin? Has CdtR further functions (in addition to binary toxin regulation)?

To address these, clean deletion mutants of cdtR have been generated in a ribotype 027 C. difficile strain (R20291, producing the large toxins A and B and also CDT) and also in CD630, containing the afore mentioned ghost locus. Furthermore the PaLoc (containing toxin A and B) has been deleted from R20291. Production of CDT is assessed in the R20291 mutants by Western blot and cytotoxicity. Effects of the CdtR deletion in a CDT negative strain are being investigated to potentially elucidate a role beyond binary toxin regulation.

The here presented study will give an insight into the role(s) and regulation of the binary toxin regulator CdtR in C. difficile.

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