Two-Component Systems of Mycobacterium tuberculosis as potential targets for drug development

Tuberculosis, caused by Mycobacterium tuberculosis, is a global health problem with approximately two million deaths every year. Furthermore, up to one-third of the world population is infected with latent form of this bacterium. Existing anti-tuberculosis therapies are directed against actively replicating bacteria, while there is no particular treatment for latent tuberculosis infection. Bacterial two-component systems (TCSs) are pleiotropic and play a central role in the adaptation of pathogenic bacteria to the environment prevailing within host tissues. TCS allow microorganisms to sense and respond to changes in many different environmental conditions therefore are considered potential pharmacological targets for the development of novel antimycobacterial drugs. In this work, we review the current knowledge of the TCSs of Mycobacterium tuberculosis. We discuss their role in bacterial pathogenesis and virulence. We pay special attention to the DosS/DosT/DosR TCS, emphasizing its importance in latent tuberculosis development.