DosRST dormancy two-component regulatory system (DosRST)

The DosRST (Dormancy survival Regulon) system is a critical two-component regulatory pathway in Mycobacterium tuberculosis (Mtb) that enables the bacterium to sense and respond to environmental stresses, particularly hypoxia, nitric oxide, and carbon monoxide (Honaker et al., 2009, Journal of Bacteriology). It consists of two sensor histidine kinases, DosS (DevS) and DosT, which detect these signals and subsequently phosphorylate the response regulator DosR (DevR). Once activated, DosR functions as a transcription factor that induces the expression of approximately 50 genes known as the dormancy regulon, facilitating a metabolic shift from active replication to a non-replicative, persistent state (Gautam et al., 2015, Journal of Biological Chemistry). This system is essential for the survival of Mtb during latent tuberculosis infection within host granulomas, where oxygen levels are low. Because the DosRST system is unique to bacteria and vital for persistence, it is a prominent target for developing drugs aimed at shortening tuberculosis treatment and eradicating latent reservoirs. Small molecules such as artemisinin and various synthetic inhibitors like HC104A have been identified to disrupt this signaling pathway, effectively preventing the induction of the dormancy program (Zheng et al., 2017, Nature Chemical Biology).

Other names

DevR-DevS systemDosR-DosS-DosT systemDormancy survival regulonDevRSTDosR pathway

Inhibition of sensor kinase (DosS/DosT) autophosphorylation or inhibition of response regulator (DosR) DNA-binding activity to prevent induction of the dormancy regulon.