University of California - San Diego
Biosynthetic Inhibition of Small Molecule Virulence Factors from Mycobacteria
Most virulent organisms produce small molecules that are essential for causing disease, usually toxins or signaling molecules. The machinery that makes these molecules is a promising target for antibiotic development. The Buruli ulcer is a tropical skin disease caused by Mycobacterium ulcerans that causes painless infections that lead to massive skin ulceration. The disease is unresponsive to contemporary antibiotics, and surgery is the most common treatment. A small molecule produced by the microbe called mycolactone has been found to be the sole cause of necrosis, and we are targeting its biosynthetic pathway for antibiotic design. The information learned here will also inform the development of antibiotics for other mycobacterial diseases, including tuberculosis and leprosy.