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Gene Review

relA  -  (P)ppGpp synthetase I

Salmonella enterica subsp. enterica serovar Typhimurium str. LT2

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Disease relevance of relA

  • Reversal of growth retardation by L-isoleucine, accumulation of guanosine 5'-diphosphate 3'-diphosphate (magic spot), and relA mutant hypersensitivity suggest sulfometuron methyl interference with branched-chain amino acid biosynthesis [1].
  • Identification and characterization of a relA-dependent starvation-inducible locus (sin) in Salmonella typhimurium [2].
  • To determine the effect of ppGpp, a stringent (relA+) and relaxed (relA) isogenic pair of E. coli K-12 strains was starved for isoleucine, and the residual rate of synthesis of this enzyme was measured [3].

High impact information on relA

  • In vivo derepression of the his operon is markedly defective when histidine starvation is imposed on a relA mutant--unable to rapidly increase synthesis of ppGpp--growing in amino-acid-rich medium [4].
  • Since not all relA-dependent sti loci are induced during both C- and N-starvation, we propose that two separate ppGpp-dependent pathways function during C-starvation and N-starvation, respectively [5].
  • In addition, derepression of his expression by novobiocin and its repression by anaerobiosis or osmolarity are independent of the stringent response gene, relA [6].
  • In addition, all four loci are under positive regulation by the relA gene product (i.e., ppGpp) during C- or N-starvation, but not P-starvation [5].
  • This role was independent of the relA gene (previously found to be needed for stiB induction) [7].

Associations of relA with chemical compounds

  • Mutants lacking 4-thiouridine (nuv) and mutants defective in the synthesis of ppGpp (guanosine 5'-diphosphate-3'-diphosphate) (relA) were found to be sensitive to killing by near-UV [8].
  • The introduction of relA into the sinA-lac strain prevented induction by nicotinate starvation and partially prevented induction by phosphate starvation [2].
  • The relA mutant again failed to resume growth after a shift from glucose-ammonia to glucose-arginine medium [9].

Other interactions of relA

  • One carbon-starvation-inducible lac fusion, designated stiA was previously reported to be a sigma(S)-dependent SSR locus that is phosphate-starvation, nitrogen-starvation and H2O2 inducible, positively regulated by (p)ppGpp in a relA-dependent manner, and negatively regulated by cAMP:cAMP receptor protein complex and OxyR [10].
  • In this study, we found that relA and spoT double mutant Salmonella (DeltappGpp strain), which is defective in ppGpp synthesis, was virtually avirulent in BALB/c mice [11].


  1. The sulfonylurea herbicide sulfometuron methyl is an extremely potent and selective inhibitor of acetolactate synthase in Salmonella typhimurium. LaRossa, R.A., Schloss, J.V. J. Biol. Chem. (1984) [Pubmed]
  2. Identification and characterization of a relA-dependent starvation-inducible locus (sin) in Salmonella typhimurium. Foster, J.W. J. Bacteriol. (1983) [Pubmed]
  3. Regulation of Escherichia coli aspartate transcarbamylase synthesis by guanosine tetraphosphate and pyrimidine ribonucleoside triphosphates. Turnbough, C.L. J. Bacteriol. (1983) [Pubmed]
  4. Guanosine 5'-diphosphate 3'-diphosphate (ppGpp): positive effector for histidine operon transcription and general signal for amino-acid deficiency. Stephens, J.C., Artz, S.W., Ames, B.N. Proc. Natl. Acad. Sci. U.S.A. (1975) [Pubmed]
  5. Starvation-inducible loci of Salmonella typhimurium: regulation and roles in starvation-survival. Spector, M.P., Cubitt, C.L. Mol. Microbiol. (1992) [Pubmed]
  6. The DNA supercoiling-sensitive expression of the Salmonella typhimurium his operon requires the his attenuator and is modulated by anaerobiosis and by osmolarity. O'Byrne, C.P., Ní Bhriain, N., Dorman, C.J. Mol. Microbiol. (1992) [Pubmed]
  7. RpoS is necessary for both the positive and negative regulation of starvation survival genes during phosphate, carbon, and nitrogen starvation in Salmonella typhimurium. O'Neal, C.R., Gabriel, W.M., Turk, A.K., Libby, S.J., Fang, F.C., Spector, M.P. J. Bacteriol. (1994) [Pubmed]
  8. Near-UV stress in Salmonella typhimurium: 4-thiouridine in tRNA, ppGpp, and ApppGpp as components of an adaptive response. Kramer, G.F., Baker, J.C., Ames, B.N. J. Bacteriol. (1988) [Pubmed]
  9. The regulation of the ammonia assimilatory enzymes in Rel+ and Rel- strains of Salmonella typhimurium. Sales, M., Brenchley, J.E. Mol. Gen. Genet. (1982) [Pubmed]
  10. The rpoS-dependent starvation-stress response locus stiA encodes a nitrate reductase (narZYWV) required for carbon-starvation-inducible thermotolerance and acid tolerance in Salmonella typhimurium. Spector, M.P., Garcia del Portillo, F., Bearson, S.M., Mahmud, A., Magut, M., Finlay, B.B., Dougan, G., Foster, J.W., Pallen, M.J. Microbiology (Reading, Engl.) (1999) [Pubmed]
  11. Immune response induced by Salmonella typhimurium defective in ppGpp synthesis. Na, H.S., Kim, H.J., Lee, H.C., Hong, Y., Rhee, J.H., Choy, H.E. Vaccine (2006) [Pubmed]
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