The Stairs Lecture in Chemistry: How Pathogens Use Traits from Environmental Bacteria to Survive in Human Hosts

The vast majority of mycobacteria live in soil and other environments where they break down an astoundingly wide range of organic compounds. This ability plays an important role in the global carbon cycle. For example, bacteria are the only organisms known to degrade and grow on steroids, using them for carbon and energy.

This talk will summarize our discovery of cholesterol degradation in an environmental bacterium, and how this helped us to understand the ability of two pernicious pathogens to survive in their human host. The first, Mycobacterium tuberculosis, is a leading cause of mortality from an infectious agent world-wide. The second, Mycobacterium abscessus, is an opportunistic pathogen responsible for non-tuberculous pulmonary infections often associated with cystic fibrosis patients.

In our journey, we used a wide variety of techniques to elucidate the step-by-step process by which these bacteria break down cholesterol and steroids. We have also used chemical and genetic approaches to probe the degradation pathway as a target for novel therapeutics that are urgently needed to decrease the length, and improve the efficacy, of treatments.