@article{94342, keywords = {Buruli ulcer}, author = {Asare KK and }, title = {Buruli Ulcer: What are the Future Perspectives in Dealing with the extensive Necrotizing Skin Disease}, abstract = {Buruli ulcer (BU) is a necrotizing skin disease cause by mycolactone-producing Mycobacteria ulcerans. The disease leaves permanent disabilities, stigmatization, a clinical challenge linked to morbidity and treatment with negative socioeconomic impact. The current effective treatment remains antibiotics combination therapies of rifampicin and streptomycin with 2-10% of the patients developing worse extensive ulcers after the treatment and there is no vaccine. In the case of extensive ulceration, the treatment option remains surgical resection and skin grafting which is very challenging and even when successful leaves scars and disability. This review focuses on the recent understanding of mechanisms upon which mycolactone-producing Mycobacteria ulcerans induces extensive skin ulcers and suggest areas within the pathological pathways which can be targeted for the future management and treatment of the disease. The mycolactone binds to Sec 61 translocon subunit and inhibits the binding immunoglobulin protein (BiP). A point mutations R66I, R66G, and S82P in the Sec61α subunit has been shown to prevent mycolactone binding to the Sec61 lumen. The mycolactone also compromised the cytoskeleton and dysregulated immunity through the activation of the AT2R receptor. Thus, targeting the mycolactone binding site either by inducing mutation or competitive inhibition compounds, blocking the AT2R receptor and the uncontrol activation ARP2/3 could revolutionize the management of extensive ulceration in BU patients.}, year = {2020}, journal = {Global Journal of Dermatology & Venereology}, volume = {8}, pages = {21-31}, publisher = {Synergy Publishers}, issn = {2310-998X}, url = {https://www.researchgate.net/profile/Kwame_Asare3/publication/343594080_Buruli_Ulcer_What_are_the_Future_Perspectives_in_Dealing_with_the_extensive_Necrotizing_Skin_Disease/links/5f33e903299bf13404bb2014/Buruli-Ulcer-What-are-the-Future-Perspectives-in-De}, doi = {10.12970/2310-998x.2020.08.04}, language = {eng}, }