Mycobacterium ulcerans infects the skin and subcutaneous tissues. It secretes a lipid toxin, mycolactone, which causes open skin lesions, known as Buruli ulcers. Laure Guenin-Macé and colleagues investigated the molecular actions of mycolactone and found that it dysregulates the actin cytokskeleton, driving uncontrolled actin polymerization by activating a protein known as N-WASP. Guenin-Macé and colleagues demonstrated that they could block the degradation process by administration of the N-WASP inhibitor wiskostatin. These results reveal the molecular pathogenesis of M. ulcerans and suggest that drugs that disrupt mycolactone/N-WASP binding could be used to treat Buruli ulcers. The accompanying images show mouse epidermis treated with vehicle (top right) and mycolactone (bottom right) as well as cells treated with mycolactone over time (left panels, increasing time, top to bottom).
Mycolactone is a diffusible lipid secreted by the human pathogen
Laure Guenin-Macé, Romain Veyron-Churlet, Maria-Isabel Thoulouze, Guillaume Romet-Lemonne, Hui Hong, Peter F. Leadlay, Anne Danckaert, Marie-Thérèse Ruf, Serge Mostowy, Chiara Zurzolo, Philippe Bousso, Fabrice Chrétien, Marie-France Carlier, Caroline Demangel