Detection of Mycolactone A/B in Mycobacterium ulcerans-Infected Human Tissue

• Published in: PLoS neglected tropical diseases Vol. 4; no. 1; p. e577
• Main Authors: Sarfo, Fred Stephen, Phillips, Richard O, Rangers, Brian, Mahrous, Engy A, Lee, Richard E, Tarelli, Edward, Asiedu, Kingsley B, Small, Pamela L, Wansbrough-Jones, Mark H
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.01.2010; Public Library of Science (PLoS)
• Subjects: Acetone; Adolescent; Adult; Animals; Apoptosis; Bacterial Toxins - chemistry; Bacterial Toxins - isolation & purification; Bacterial Toxins - pharmacology; Biological properties; Buruli Ulcer - metabolism; Buruli Ulcer - microbiology; Cell cycle; Cell Line; Child; Chromatography, Thin Layer; Cytotoxicity; Experiments; Female; Humans; Infections; Infectious Diseases/Bacterial Infections; Lesions; Lipids; Macrolides; Macrophages - drug effects; Macrophages - metabolism; Male; Mice; Mycobacterium; Mycobacterium ulcerans; Mycobacterium ulcerans - metabolism; Mycobacterium ulcerans - physiology; Pathogenesis; Proteins; Skin - metabolism; Skin - microbiology; Skin - pathology; Spectrometry, Mass, Electrospray Ionization; Thin layer chromatography; Toxins; Tropical diseases; Tumor Necrosis Factor-alpha - metabolism; Ulcers; Young Adult; West Africa; Cell Line; Macrolides; Humans; Male; Chromatography, Thin Layer; Macrophages; Tumor Necrosis Factor-alpha; Young Adult; Mycobacterium ulcerans; Animals; Spectrometry, Mass, Electrospray Ionization; Bacterial Toxins; Adolescent; Adult; Female; Buruli Ulcer; Mice; Skin; Child
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0000577

Mycobacterium ulcerans disease (Buruli ulcer) is a neglected tropical disease common amongst children in rural West Africa. Animal experiments have shown that tissue destruction is caused by a toxin called mycolactone. A molecule was identified among acetone-soluble lipid extracts from M. ulcerans (Mu)-infected human lesions with chemical and biological properties of mycolactone A/B. On thin layer chromatography this molecule had a retention factor value of 0.23, MS analyses showed it had an m/z of 765.6 [M+Na(+)] and on MS:MS fragmented to produce the core lactone ring with m/z of 429.4 and the polyketide side chain of mycolactone A/B with m/z of 359.2. Acetone-soluble lipids from lesions demonstrated significant cytotoxic, pro-apoptotic and anti-inflammatory activities on cultured fibroblast and macrophage cell lines. Mycolactone A/B was detected in all of 10 tissue samples from patients with ulcerative and pre-ulcerative Mu disease. Mycolactone can be detected in human tissue infected with Mu. This could have important implications for successful management of Mu infection by antibiotic treatment but further studies are needed to measure its concentration.