(p)ppGpp-dependent activation of gene expression during nutrient limitation
Bibliographic record
Abstract
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 called (p)ppGpp. In addition, genes encoding proteins that facilitate survival during nutrient limitation exhibit increased expression. An example is the hpf gene, which encodes 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 Bacillus subtilis cells exit rapid growth. Specifically, we demonstrate that hpf transcription during nutrient limitation requires an RNA polymerase holoenzyme containing the alternative sigma factor σ H , 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. IMPORTANCE Bacteria often experience nutrient limitation and, in response, attenuate energetically costly metabolic processes like protein synthesis. At the same time, however, they stimulate the expression of a subset of proteins that facilitate survival under these conditions. This study identifies a molecular mechanism in the model gram-positive bacterium Bacillus subtilis responsible for gene expression in response to nutrient limitation that couples reduced global protein synthesis with increased transcription of specific genes. This mechanism mediates the elaboration of developmental fates, including sporulation and genetic competence, which are known responses to nutrient limitation in this organism.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".