Characterization of Novel Macrolide Toxins, Mycolactones A and B, from a Human Pathogen, Mycobacterium ulcerans

• Published in: Journal of the American Chemical Society 1999-06, Vol.121 (25), p.6092-6093
• Main Authors: Gunawardana, Geewananda, Chatterjee, Delphi, George, Kathleen M, Brennan, Patrick, Whittern, David, Small, P. L. C
• Format: Article
• Language: English
• Subjects: macrolides; Mycobacterium ulcerans; mycolactone A; mycolactone B
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja990017l

Mycobacterium ulcerans causes a severe skin disease, Buruli ulcer characterized by extensive necrosis in the absence of an acute inflammatory response. Even though the better known pathogenic members of the genus Mycobacterium, such as Mycobacterium tuberculosis and Mycobacterium leprae, are not associated with toxins, the possible presence of a toxin in M. ulcerans, which is an extracellular pathogen, has been hypothesized for a number of years. Despite several attempts, no compound responsible for the cytopathic effect of this organism has been identified. Partial purification of the toxin and evidence that it was a lipophilic molecule were reported earlier. The spectral analyses of the toxin lead to the identification of two compounds which were named mycolactones A and B. The structure elucidation of the two compounds is described in this paper. This is the first identification of a macrolide produced by a human pathogen, as well as the only macrolide identified in the genus Mycobacterium.