"Recognizing a surprising fact is the first step towards discovery." This famous quote from Louis Pasteur is particularly appropriate to describe what led us to study mycolactone, a lipid toxin produced by the human pathogen . is the causative agent of Buruli ulcer, a neglected tropical disease manifesting as chronic, necrotic skin lesions with a "surprising" lack of inflammation and pain. Decades after its first description, mycolactone has become much more than a mycobacterial toxin. This uniquely potent inhibitor of the mammalian translocon (Sec61) helped reveal the central importance of Sec61 activity for immune cell functions, the spread of viral particles and, unexpectedly, the viability of certain cancer cells. We report in this review the main discoveries that marked our research into mycolactone, and the medical perspectives they opened up. The story of mycolactone is not over and the applications of Sec61 inhibition may go well beyond immunomodulation, viral infections, and oncology.
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| http://dx.doi.org/10.3390/toxins15060369 | DOI Listing |
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Computational and GC-MS screening of bioactive compounds from Thymus Vulgaris targeting mycolactone protein associated with Buruli ulcer.
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Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.
Buruli ulcer (BU) a neglected disease induced by the bacterium Mycobacterium ulcerans, predominantly impacts tropical and subtropical areas with its pathophysiology ascribed to the Mycolactone protein. Current antibiotics frequently prove insufficient to manage advanced or chronic ulcers and the rise of drug resistance presents a considerable challenge. This work aims to address these challenges by employing computational methods to identify therapeutic candidates from organic compounds, which may be developed into more effective therapies for Buruli ulcer.
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Toxins (Basel)
December 2024
Department of Chemistry, University of Ghana, Legon-Accra P.O. Box LG56, Ghana.
Mycolactone is a complex macrolide toxin produced by , the causative agent of Buruli ulcer. The aim of this paper is to review the chemistry, biosynthetic, and synthetic pathways of mycolactone A/B to help develop an understanding of the mode of action of these polyketides as well as their therapeutic potential. The synthetic work has largely been driven by the desire to afford researchers enough (≥100 mg) of the pure toxins for systematic biological studies toward understanding their very high biological activities.
View Article and Find Full Text PDFBuruli ulcer: An epidemiological update from Japan.
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January 2025
Department of Tropical Medicine and Infectious Disease, Tulane School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
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Department of Tropical Medicine and Infectious Disease, Tulane School of Public Health and Tropical Medicine, New Orleans, USA.
Buruli ulcer, caused by , is a neglected tropical disease (NTD) characterized by necrosis of the cutaneous tissue, predominantly affecting the limbs. The pathogenesis of this disease is mainly attributed to mycolactone, a lipid toxin produced by . Here, we report the case of a 7-year-old Japanese girl who presented with worsening ulceration on her left forearm, extending to the elbow, following antimicrobial treatment.
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J Clin Tuberc Other Mycobact Dis
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Kumasi Centre for Collaborative Research into Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
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