(p)ppGpp-dependent activation of gene expression during nutrient limitation

ABSTRACT: As rapidly growing bacteria begin to exhaust nutrients, their growth rate slows, ultimately leading to stasis or quiescence. Adaptation to nutrient limitation requires widespread metabolic remodeling that leads to lower cellular energy consumption. Examples of such changes include attenuated transcription of genes encoding ribosome components, in part mediated by the phosphorylated nucleotides guanosine tetra- and penta-phosphate, collectively (p)ppGpp. In addition, genes such as those encoding specific proteins that facilitate survival exhibit increased expression during nutrient limitation. An example is the hpf gene, encoding a broadly conserved protein responsible for protecting the ribosome from degradation under conditions limiting for ribosome synthesis. Here we show that (p)ppGpp plays a key role in the transcriptional activation of hpf as B. subtilis cells exit rapid growth. Specifically, we demonstrate that hpf transcription during nutrient limitation requires an RNAP holoenzyme containing the alternative sigma factor σH, encoded by sigH, whose expression is normally inhibited by the AbrB repressor. However, when global protein synthesis decreases, in part dependent on (p)ppGpp, AbrB levels fall, leading to increased sigH transcription and consequently hpf activation. This mechanism couples a key physiological consequence of nutrient limitation – reduced protein synthesis – with specific gene activation, thereby linking transcriptional and translational regulation. Finally, we demonstrate that (p)ppGpp is necessary for the gene expression underlying the elaboration of developmental fates including sporulation and genetic competence. Thus, the active attenuation of protein synthesis by (p)ppGpp is not only necessary for the conservation of energetic resources but also for the proper pattern of gene activation during transition to quiescence.

ORGANISM(S): Bacillus subtilis subsp. subtilis str. 168

PROVIDER: GSE303058 | GEO | 2025/08/04

REPOSITORIES: GEO