The (p)ppGpp regulon of R. etli. The extensive impact of (p)ppGpp on gene expression of R. etli is illustrated by the number of up- and downregulated genes grouped according to functional categories. The remaining categories are combined as 'Other processes'. The rsh mutant is unable to synthesize (p)ppGpp and has a pleiotropic phenotype, such as an altered morphology, increased stress sensitivity and impaired symbiosis. As a global regulator, the regulon of (p)ppGpp is multilayered. Further insight into the (p)ppGpp-dependent stress response was obtained by the identification and subsequent characterization of three different regulators that are under strong positive regulation of (p)ppGpp during stationary phase. EcfG2/PF00052 and RpoE4, both ECF sigma factors, are partly functionally redundant for survival under heat stress and oxidative stress. The transcription factor CH00371 is also involved in survival during both heat and oxidative stress. PrkA, a serine kinase, likely plays a role in the (p)ppGpp-dependent adaptation of the cellular metabolism. Its transcription is positively controlled by RpoN1 and negatively autoregulated.