In Mycobacterium tuberculosis, the sensor kinases DosT and DosS activate the 
transcriptional regulator DosR, resulting in the induction of the DosR regulon, 
which is important for anaerobic survival and perhaps latent infection. The 
individual and collective roles of these sensors have been postulated 
biochemically, but their roles in vivo have remained unclear. This work 
demonstrates distinct and additive roles for each sensor during anaerobic 
dormancy. Both sensors are necessary for wild-type levels of DosR regulon 
induction, and concomitantly, full induction of the regulon is required for 
wild-type anaerobic survival. In the anaerobic model, DosT plays an early role, 
responding to hypoxia. DosT then induces the regulon and with it DosS, which 
sustains and further induces the regulon. DosT then loses its functionality as 
oxygen becomes limited, and DosS alone maintains induction of the genes from 
that point forward. Thus, M. tuberculosis has evolved a system whereby it 
responds to hypoxic conditions in a stepwise fashion as it enters an anaerobic 
state.