Understanding Signal Transduction system of kdpD in Mycobacterium Tuberculosis
Mycobacterium tuberculosis (Mtb) is a facultative intracellular pathogen and is estimated to infect about one-third of the world’s population. Long term survival of Mtb depends on its ability to sense and adapt to adverse conditions which includes hypoxia, nutrient limitation, osmotic imbalance, pH alterations, cell wall/membrane stress inside the host. Adaptations to environmental signals are associated with transcriptomic changes driven by various regulators including the two-component systems. Mtb has 11 paired two-component systems out of which two systems kdpDE and NarSL named based on their homology with the corresponding E.coli two-component system are still not characterized. In Escherichia coli, the primary response to environmental osmotic stress is the regulation of potassium content in the cytoplasm through kdpD mediated signaling which in turn produce K+transporting P type ATPase by transcribing kdpFABC operon. Functional characterization of MtbkdpD and its downstream factors is required to understand the Mtb physiology under osmotic stress. Detailed study of the signaling pathway mediated by kdpD may help us to understand the Mtb survivability inside host. Here we will explore the possibility that the USP (Universal Stress Protein) domain of kdpD binds cyclic-di-nucleotides. Tuberculosis (TB) remains a global epidemic, with one-third of the world's population infected and approximately 9 million new active cases annually. The TB epidemic is exacerbated by a synergy with human immunodeficiency virus (HIV) and steadily increasing rates of drug resistance. The efficacy of the only vaccine strain, Mycobacterium bovisBCG, varies from 0 to 80% in preventing pulmonary TB. Therefore, new strategies for TB therapy and novel vaccines for eradication of the infection are urgently needed. A better understanding of the signaling mechanism of Mycobacterium tuberculosiscould facilitate these goals.
Keywords: kdpD, Mycobacterium tuberculosis, Escherichia coli, Cyclic-di-nucleotides.