Screening Mycobacterium tuberculosis hits against Mycobacterium ulcerans
Buruli ulcer, caused by Mycobacterium ulcerans, is a neglected tropical disease that, if left untreated, can cause debilitating skin ulcers and destruction of soft tissue. Current treatment involves eight weeks of antibiotics, a difficult course to implement in resource-limited settings. Drs. Pluschke and Scherr were interested in screening compounds against Buruli ulcer that had showed promise in screens against M. tuberculosis, as M. ulcerans is closely related to M. tuberculosis. BVGH facilitated a collaboration with AstraZeneca, which shared 100 anti-tuberculosis compounds (including one in clinical trials) for the Swiss TPH investigators to screen in their Buruli ulcer assay. While a number of potent antitubercular agents were only weakly active or inactive against M. ulcerans, five compounds showed high activity, making screening of focused antitubercular libraries a good starting point for lead generation against M. ulcerans.