Mycolactone: A Polyketide Toxin from Mycobacterium ulcerans Required for Virulence

• Published in: Science (American Association for the Advancement of Science) Vol. 283; no. 5403; pp. 854 - 857
• Main Authors: George, Kathleen M., Chatterjee, Delphi, Gunawardana, Geewananda, Welty, Diane, Hayman, John, Lee, Richard, Small, P. L. C.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 05.02.1999; American Association for the Advancement of Science
• Subjects: Animals; Bacterial Toxins - chemistry; Bacterial Toxins - isolation & purification; Bacterial Toxins - toxicity; Bacteriology; Biological and medical sciences; Cell cycle; Cell Cycle - drug effects; Cells; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Development and progression; Female; Fundamental and applied biological sciences. Psychology; Guinea Pigs; L Cells (Cell Line); Lactones; Lesions; Lipids; Macrolides; Mass Spectrometry; Mice; Microbiology; Mycobacterial infections; Mycobacterium infections; Mycobacterium Infections, Nontuberculous - microbiology; Mycobacterium Infections, Nontuberculous - pathology; Mycobacterium ulcerans; Mycobacterium ulcerans - chemistry; Mycobacterium ulcerans - pathogenicity; Necrosis; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Pathology; Polyketides; Skin - microbiology; Skin - pathology; Skin Diseases, Bacterial - microbiology; Skin Diseases, Bacterial - pathology; Toxins; Ulcers; Virulence; Toxicity; Rodentia; Host agent relation; In vitro; Macrolide; Biological activity; Characterization; In vivo; Toxin; Vertebrata; Mycobacterium ulcerans; Mammalia; Guinea pig; Mycobacteriales; Mycobacteriaceae; Bacteria; Actinomycetes
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.283.5403.854

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 1929 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.