Fellowship: Tyler Bucci: Elucidating the pathway of mycobacterial cholesterol catabolism

Tuberculosis (TB), caused primarily by Mycobacterium tuberculosis (Mtb), remains one of the deadliest communicable diseases and is notorious for its cumbersome treatment regimen, which often consists of a three-drug cocktail administered for 6-9 months. Our long-term goal is to develop novel therapeutics effective against persistent TB including both drug-sensitive and drug-resistant TB. We hypothesize that cholesterol metabolism—specifically the oxidative degradation of the aliphatic side chain of cholesterol—is an ideal target for eradicating persistent TB. To test this hypothesis, we will functionally assign the proteins required for this pathway, most of which have not been defined for Mtb, and develop a high throughput activity-based assay to screen for potential inhibitors.