Figure 4.

Summary of the effects of (p)ppGpp in Mtb. The RelMtb synthetase domain transfers the 5΄-β,γ-pyrophosphate from ATP to the 3΄-OH of GDP or GTP to synthesize (p)ppGpp, which can then be hydrolyzed by the RelMtb hydrolase domain. (p)ppGpp accumulates in response to a number of stresses, including starvation and oxidative stress, leading to alterations in purine metabolism, gene expression and polyP metabolism. It is also possible that there are other unidentified targets of (p)ppGpp in Mtb. These effects of (p)ppGpp accumulation contribute to enhanced virulence, persistence and stress responses.