Research Summary

Intermediate Fellowship research summary

Mycobacterium tuberculosis (Mtb) is an extremely successful pathogen due to its ability to latently infect more than one third of the world’s population. How Mtb can persist in human tissues for decades without replicating and then abruptly resume its growth and cause disease is a fundamental question in the tuberculosis field.

The role of redox signaling molecules such as oxygen (O2) and nitric oxide (NO) in promoting Mtb persistence has received wide attention. However, the molecular mechanism of how these diatomic gases are sensed to induce Mtb persistence remains elusive. Our work suggests that the Mtb WhiB family functions as a Fe-S based “sensor system” to precisely monitor O2, NO and cellular redox stress to promote bacterial persistence. This research proposal investigates the function of the WhiB proteins in controlling dormancy and reactivation of Mtb.

We plan to exploit EDFS-EPR to analyze the Fe-S clusters of WhiB proteins and utilize a novel protein interaction technology (M-PFC) to generate a network of proteins which communicate with the WhiB proteins. We will analyze the regulatory role of WhiB proteins in response to oxido-reductive stress. Lastly, our plan is to investigate the in vivo role of the WhiB family using various animal models.