Stringent response pathway in bacteria

The **stringent response pathway in bacteria** is a conserved global regulatory mechanism, not a single molecule or receptor, triggered under nutrient deprivation, stress, or antibiotic challenge[2][3][6]. This pathway is mediated primarily by accumulation of the alarmone nucleotides **(p)ppGpp (guanosine tetra- and pentaphosphate)**, synthesized by RelA/SpoT homologues (RSHs), including RelA and SpoT in _Escherichia coli_, or by Rel_Mtb_ in _Mycobacterium tuberculosis_[2][3][6]. The stringent response swiftly reprograms bacterial gene expression: it represses biosynthesis of ribosomes, DNA replication, and cell growth, while upregulating genes involved in amino acid biosynthesis, stress tolerance, and survival, allowing cells to enter a dormant-like state to withstand unfavorable conditions[1][3][5]. This pathway is deeply implicated in persistent infections, chronic biofilms, immune evasion, and antibiotic tolerance, and thus presents a promising, though complex, target for anti-infective drug development[2][3][5]. However, the pathway is **not a defined molecular drug target**, but a regulatory network/process; thus, listings of drugs and mechanisms refer to efforts to disrupt this signaling axis rather than bind a specific canonical protein or receptor.\n\n**Note**\n- This entry is **not a standard molecular drug target, receptor, enzyme, or protein, but a physiological pathway/process**[2][6].\n- Standard drug target categorizations (receptor, enzyme, etc.) do not directly apply; efforts to target the pathway focus on its alarmone mediators (e.g., (p)ppGpp) or the RSH enzymes.\n- For proper structured entries, the actual target would be one of the core enzymes (_e.g._, RelA, SpoT, or (p)ppGpp itself) rather than the pathway as a whole.\n\n- is_target: **false** — the pathway itself is not a direct drug target\n- is_incorrect: **true** — this entry does _not_ correspond to a single canonical molecular target

Other names

Stringent controlSR(p)ppGpp-mediated stress response

Inhibition of (p)ppGpp synthesis, Disruption of stress signaling, Suppression of global stress adaptation