pppGpp

pppGpp, short for guanosine pentaphosphate, is a member of the alarmone nucleotides known as (p)ppGpp. It is produced by bacteria in the stringent response, a regulatory program activated by nutrient limitation and other stresses to reprogram cellular metabolism and growth.

Biosynthesis and turnover of pppGpp are carried out by RelA/SpoT homologs. RelA is a ribosome-associated synthetase that responds to amino acid starvation, while SpoT and related enzymes can both synthesize and hydrolyze (p)ppGpp in response to diverse stresses. The relative levels of pppGpp and its related compound ppGpp and their overall pool are modulated by growth conditions, nutrient availability, and stress signals. The molecules are rapidly turned over when conditions improve.

Mechanistically, pppGpp binds to RNA polymerase in cooperation with transcription factors such as DksA, leading to a reprogramming of transcription. Common outcomes include strong downregulation of ribosomal RNA and transfer RNA synthesis, reduced ribosome biogenesis, and adjustments to global metabolism. At the same time, genes involved in amino acid biosynthesis, stress response, and nucleotide metabolism may be upregulated, aligning cellular activity with available resources.

Physiological relevance of pppGpp spans growth control, stress tolerance, and virulence in various bacteria. The stringent response helps bacteria survive nutrient limitation, rapid environmental changes, and exposure to antibiotics, and it influences persistence in some pathogens. Because (p)ppGpp signaling impacts essential processes such as transcription, translation, and metabolism, it is a focus of research into bacterial physiology and potential antimicrobial strategies.

pppGpp has been studied in many bacteria, including Escherichia coli and Bacillus species, and is also relevant to chloroplasts in plants. Detection typically involves chromatographic or mass spectrometric methods to quantify (p)ppGpp levels under different conditions.