Grant: Operating Grant

Buruli ulcer (BU) caused by Mycobacterium ulcerans (MU) is an emerging disease of the wet tropical and subtropical zones that is closely related to tuberculosis and leprosy. The disease starts insidiously with a painless nodule, plaques or oedema that will lead to ulcer and formation of scar tissue. The release of mycolactone, a toxin produced by MU, appears to induce the necrosis and pathological processes. Because of the lack of simple, cheap, effective treatment modalities, BU is an extremely destructive and expensive problem in endemic areas. Our central hypothesis is that tissue damage following BU goes well beyond skin and underlying skeletal muscles are locally and possibly systematically affected by MU. Throughout this grant proposal, we will use in vitro and in vivo experiments to characterize and understand MU infection. More precisely, mice will be employed to characterize the inflammatory response and scarring in skeletal muscles following wild type MU and negative mycolactone mutant MU infection. In addition, we will evaluate muscle damage and repair after mycolactone injection. Interestingly, the presence of mycolactone not only causes muscle damage but also prevents muscle regeneration to occur. Finally, we will try to identify by which molecular pathways MU/mycolactone induce myotube atrophy in vitro. We strongly believe that this research proposal will provide additional insights into MU infection, which will pave the way to reducing muscle fibrosis and atrophy thereby promoting repair tissue.