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Mycolactone: a polyketide toxin from Mycobacterium ulcerans required for virulence.

Science (New York, N.Y.)

Virulence, Bacterial Toxins, chemistry, isolation & purification, toxicity, Cell Cycle, drug effects, Chromatography, High Pressure Liquid, Chromatography, Thin Layer, Female, Guinea Pigs, L Cells (Cell Line), Macrolides, Mass Spectrometry, Animals, Mice, Mycobacterium Infections, Nontuberculous, microbiology, pathology, Mycobacterium ulcerans, pathogenicity, Necrosis, Skin, Skin Diseases, Bacterial

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      Abstract

      Mycobacterium ulcerans is the causative agent of Buruli ulcer, a severe human skin disease that occurs primarily in Africa and Australia. Infection with M. ulcerans results in persistent severe necrosis without an acute inflammatory response. The presence of histopathological changes distant from the site of infection suggested that pathogenesis might be toxin mediated. A polyketide-derived macrolide designated mycolactone was isolated that causes cytopathicity and cell cycle arrest in cultured L929 murine fibroblasts. Intradermal inoculation of purified toxin into guinea pigs produced a lesion similar to that of Buruli ulcer in humans. This toxin may represent one of a family of virulence factors associated with pathology in mycobacterial diseases such as leprosy and tuberculosis.

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      9933171

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