Mycobacterium ulcerans is the causative agent of Buruli Ulcer (BU), a neglected tropical disease characterized by extensive necrotic skin lesions. M. ulcerans, although an intracellular pathogen, is able to secrete a cytotoxic and immunosuppressive toxin – mycolactone. This apparent paradox of an intracellular lifestyle with the secretion of a cytotoxic toxin can be reconciled if one considers that metabolic cues can regulate mycolactone production, possibly by turning off the synthesis of mycolactone during intramacrophagic growth and later switching on toxin production for the lysis of the infected cell.
To fully understand the role of metabolism in the persistence and pathogenicity of M. ulcerans, the present proposal has two main goals: (1) perform the first global characterization of the host metabolic response during M. ulcerans infection and (2) regulate the main metabolic events that occur in the context of M. ulcerans infection to determine their impact on the immune response and the progression of infection.