The role of two-component systems in the physiology of Mycobacterium tuberculosis

Tuberculosis is a global health problem, with a third of the world's population infected with the bacillus, Mycobacterium tuberculosis. The problem is exacerbated by the emergence of multidrug resistant and extensively drug resistant strains. The search for new drug targets is therefore a priority for researchers in the field. The two-component systems (TCSs) are central to the ability of the bacterium to sense and to respond appropriately to its environment. Here we summarize current knowledge on the paired TCSs of M. tuberculosis. We discuss what is currently understood regarding the signals to which each of the sensor kinases responds, and the regulons of each of the cognate response regulators. We also discuss what is known regarding attempts to inhibit the TCSs by small molecules and project their potential as pharmacological targets for the development of novel antimycobacterial agents. © 2018 IUBMB Life, 70(8):710-717, 2018.