How Does Mycobacterium Tuberculosis Adapt to Life in Humans?
Tuberculosis is the leading cause of death worldwide from infectious diseases. To survive in the human host for decades, Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, needs to be able to "see" where it is in the body, and sense and respond appropriately to environmental signals in its immediate surroundings. We will study how Mtb may use potassium as one such critical environmental signal during infection. Potassium is the most abundant positively-charged ion within cells in our body and also in bacterial cells. Understanding how Mtb responds to potassium will lay the foundation for seeking ways to disrupt this signaling, thereby decreasing the bacterium's ability to colonize and cause disease.
Update: In the past year, we have discovered that Mtb has a unique gene expression response to potassium; at the same time, perturbation of potassium uptake by Mtb alters the bacterium's response to other key environmental signals, highlighting the importance of signal integration by Mtb. We find that potassium concentration changes in the host cell compartment in which the bacteria reside, and that maintenance of potassium homeostasis impacts on the ability of Mtb to grow in host cells. These results illustrate the important role that potassium can play in tuberculosis disease.