Summary

Mycobacterium ulcerans relies on its unique exotoxin known as mycolactone to cause Buruli ulcer (BU) disease. While this key virulence factor is an ideal target for drug development - as well as an ideal diagnostic target - there has not been a BU drug development activity focused on this crucial target, due to difficulties in detecting the polyketide exotoxin in samples. In this proof-of-concept study, we devised a screening platform comprising a simple mycolactone-detecting ELISA that we previously developed and showed that this screening platform is able to identify compounds that interfere with mycolactone expression in significantly higher throughput and cost-effectiveness than was previously possible. Thus, for the first time, we showed the feasibility of developing anti-virulence treatments for BU. This study has spawned an ongoing ESCMID-funded project to screen curated libraries of drugs in clinical use to identify those with the highest repurposing potential for further development as novel anti-virulence treatments for BU. We envisage that such novel therapies will improve the current BU treatment regimen.