Clostridium difficile infection (CDI) causes diseases such as antibiotic-associated diarrhoea and pseudomembranous colitis. The Centre for Disease Control and Prevention (CDC) classifies C. difficile as an immediate public health threat that requires urgent and aggressive action. Currently there are 250,000 infections and 14,000 deaths annually in the U.S, costing US$1 billion in excess medical costs.
The traditional therapies for CDI are failing, resulting in an increase in the rate of recurrent CDI. Currently, the best alternative treatment for CDI is a procedure called a faecal microbiota transplant, which restores the patient’s normal intestinal microbiota. This procedure is unpleasant, invasive and requires vigorous donor screening, which can be expensive. There is a clear need for other alternate or adjunctive treatment options for CDI.
This project will investigate the potential of Auranofin as a treatment for CDI. Auranofin is a gold salt licensed to treat arthritis. It has been shown to form a stable adduct with selenium, thereby disrupting the selenium-dependent anaerobic pathways in C. difficile. The potential of Auranofin as a therapy for CDI has not been tested in in vivo models or clinical trials.
The aim of this project is to characterise the effect of interrupting selenium metabolism. A number of in vitro assays will be used to test the effect Auranofin has on the growth, sporulation and cytotoxicity of clinical ribotype MDU-064. A sequence of C. difficile clinical isolates will be screened using Sanger sequencing to confirm that the selenoprotein targets are conserved. Preliminary results from these assays indicate that Auranofin inhibits the growth of C. difficile and could inhibit the production and/or activity of C. difficile toxin B, a primary virulence factor. The potential outcome of this project will be a novel treatment for CDI that can be tested in a small scale clinical trial at Barwon Health.