Mycolactone: A polyketide toxin from Mycobacterium ulcerans required for virulence

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