Biochemical and Functional Characterization of the Mycobacterial PdtaS-PdtaR Two Component System

Abstract

Two-Component Systems (TCSs) are primarily prokaryotic modes of cell signaling involving a receptor sensor kinase (SK) that senses stimuli and a response regulator (RR) that effects a response, usually at the level of transcriptional regulation. It has been shown that the human pathogen Mycobacterium tuberculosis uses TCSs to adapt to various conditions inside the host during infection and they play roles in host cell entry, intracellular survival and division as well as hypoxia and dormancy. However, one of the major roadblocks in our understanding of TCSs stem from the lack of identified ligands that activate TCS SKs. Most studies involving TCSs have made use of gene knockouts to study the TCS in its ‘off’ state and derive possible functions of the TCS from this data. Currently, only 3 out of 13 SKs have known ligands and 4 out of a total of 12 paired TCSs are of unknown function.