(p)ppGpp, guanosine pentaphosphate and tetraphosphate, also known as the "magic spot" nucleotides,[1] are alarmones involved in the stringent response in bacteria that cause the inhibition of RNA synthesis when there is a shortage of amino acids.

[4] These nucleotides were found to accumulate rapidly in Escherichia coli cells starved for amino acids and inhibit synthesis of ribosomal and transfer RNAs.

Historically, literature surrounding (p)ppGpp have given conflicting findings and information on its role in bacterial stress responses.

[7] A complete absence of (p)ppGpp causes multiple amino acid requirements, poor survival of aged cultures, aberrant cell division, morphology, and immotility, as well as being locked in a growth mode during entry into starvation.

When the amino acid balance in the cell is restored, (p)ppGpp is hydrolyzed by SpoT and returned to a more energetically favorable state.

Most other bacteria encode a single protein that is responsible for both synthesis and degradation of (p)ppGpp, generally homologs of SpoT.

There is now a consensus that (p)ppGpp is a determinant of growth rate control rather than nucleoside triphosphate (NTP) substrate concentrations.

In B. subtilis, the replication arrest due to (p)ppGpp accumulation is caused by the binding of an Rtp protein to specific sites about 100-200kb away from oriC in both directions.

Unlike E. coli, B. subtilis accumulates more pppGpp than ppGpp; the more abundant nucleotide is a more-potent DnaG inhibitor.

Modest ppGpp levels inhibit pR and active pE, pI, and paQ promoters in vivo and have effects in vitro that seem to favor lysogeny.

One of the key elements of promoters inhibited by (p)ppGpp is the presence of a GC-rich discriminator, defined as a region between TATA-box (-10 box) and +1 nt (where +1 is the transcription start site).

Two conserved acidic residues at the tip of the finger domain are necessary to induce RNAP's intrinsic ability to cleave backtracked RNA.

Vaccine tests reveal that 30 days after single immunization with the (p)ppGpp0 strain, mice were protected from challenge with wild-type Salmonella at a dose 106-fold above the established LD50.