*3.4. Stress Associated Approaches*

## DosRST Signaling

*M. tuberculosis* exploits its two-component system DosRST to establish a dormant state of nonreplicating persistence (NRP) [120]. As *dosRST* mutants show attenuated growth in animal models, including nonhuman primates and guinea pigs, DosRST might be a potential target to reduce mycobacterial virulence [121]. When investigating compounds for their effect on the DosRST system, Zheng et al. identified two candidates (HC104A and HC106A) which interact with distinct members of the two-component system and decrease production of hypoxia-induced triacylglycerol by around 50% during NRP [122]. In a hypoxic shift-down model using a DosR-dependent fluorescent strain CDC1551(*hspX'::*GFP) HC106A was found to affect *M. tuberculosis* survival during NRP. HC104A on the other hand did not attenuate growth in this setting. The in vivo relevance for these interesting findings still needs to be established in a suitable animal model.
