Awardees

Lisa J Lojek  |  Sassetti Lab  |  F32 Award

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, and the leading cause of death by infectious disease. Mtb is an intracellular pathogen which is dependent on host nutrients in order to survive. Amongst these are the four primary carbon sources that Mtb uses for energy production and the production of metabolic intermediates. However, since Mtb resides in the macrophage phagolysosome, the bacteria are exposed to a variety of cellular stresses, including reactive nitrogen species (RNS) stress. Previous work from Rhee, et al. evaluating the effect of RNS stress on Mtb identified multiple essential proteins within glycolysis and metabolic intermediate production which were targeted by this type of intracellular stress. Additionally, unpublished work from our own lab showed that genes involved in glycolysis and glycerol metabolism are less essential than genes involved in fatty acid and cholesterol metabolism. Based on these data, we hypothesized that RNS stress specifically targets glycolysis which leads to the bacterium becoming more dependent on fatty acids and cholesterol for energy production. This project focuses on defining the effect of cellular reactive nitrogen species stress on carbon utilization for Mycobacterium tuberculosis and how Mtb regulates these changes in response to immune pressures.