02189nas a2200241   4500000000100000008004100001260002700042653002100069653002200090653001700112653002100129653002700150653000900177653001400186100001300200700001500213245010000228856006000328300001200388490000700400520151500407022002501922       2023                            d  bSwiss Chemical Society10aGeneral Medicine10aGeneral Chemistry10aBuruli ulcer10aDrug repurposing10aMycobacterium ulcerans10aQ20310atelacebec1 aWarryn L1 aPluschke G00aRepurposing of Tuberculosis Drug Candidates for the Treatment of Mycobacterium ulcerans Disease  uhttps://www.chimia.ch/chimia/article/view/2023_577/6291  a577-5810 v773 a<p>Buruli ulcer (BU) is a chronic necrotizing skin disease caused by Mycobacterium ulcerans. Historically, the disease was treated by surgical excision of the skin lesions, until an 8-week combination therapy of rifampicin and streptomycin was introduced in 2004. This treatment modality was effective and reduced recurrence rates. Rifampicin is the most efficacious antibiotic for the treatment of BU and, should rifampicin-resistant M.&nbsp;ulcerans strains emerge, there is currently no replacement for it. As for mycobacterial diseases in general, there is a pressing need for the development of novel, fast-acting drugs. Under market economy conditions, repurposing of new tuberculosis drug candidates is the most promising avenue for alternative BU treatments. Our drug repurposing activities have led to the identification of several actives against M.&nbsp;ulcerans. In particular, the cytochrome bc1 complex inhibitor telacebec (Q203) is a promising drug candidate for the treatment of BU in Africa and Australia. While an active cytochrome-bd oxidase bypass limits the potency of the cytochrome-bc1-specific inhibitor telacebec against M.&nbsp;tuberculosis, classical lineage M.&nbsp;ulcerans strains rely exclusively on cytochrome-bc1 to respire. Hence, telacebec is effective at nanomolar concentration against M.&nbsp;ulcerans, and a high treatment efficacy in an experimental mouse infection model indicates that treatment of BU could be substantially shortened and simplified by telacebec.</p>
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