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Gene Review

crp  -  cAMP-activated global transcriptional...

Salmonella enterica subsp. enterica serovar Typhimurium str. LT2

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Disease relevance of crp

  • The Salmonella cya crp vaccine vector was shown to incorporate into 987P partially degraded chimeric subunits lacking the TGEV epitopes [1].
  • A delta asd S. typhi strain attenuated by deletions in cya, crp, and cdt which contains hepatitis B core (HBc) and pre-S genes encoded on an Asd+ pBR-based plasmid vector was constructed [2].
  • A leu-500 leu-2012 strain containing a crp mutation (cAMP receptor protein deficiency), on the other hand, could not make leu enzymes even in the presence of cAMP [3].
  • The spike protein from transmissible gastroenteritis virus (TGEV) was expressed in attenuated S. typhimurium delta cya delta crp delta asd chi 3987 [4].
  • Characterization of transmissible gastroenteritis coronavirus S protein expression products in avirulent S. typhimurium delta cya delta crp: persistence, stability and immune response in swine [4].

High impact information on crp

  • Compared to the ssaH promoter, the Salmonella cya crp vector elicited significantly higher levels of mucosal and systemic antibodies in orally immunized mice when the chimeric fimbriae were expressed from the spiC promoter [1].
  • In this study, we constructed strain KR21 (chi 4550 delta cya delta crp delta asd/pYA292asd(+)-toxC+) and compared it with BRD847 (aroA aroD/pnirB-toxC) for the ability to induce humoral and cellular immunity after a single oral or intravenous immunization in 3- to 4-week-old BALB/c mice [5].
  • To facilitate the stable expression of heterologous genes without conferring antibiotic resistance, a deletion of the asdA1 gene was introduced into Salmonella typhimurium and S. typhi delta cya delta crp mutant vaccine strains [6].
  • The recombinant plasmid was termed SMM202 and transformed into Salmonella typhimurium chi 4072, an attenuated delta cya delta crp mutant [7].
  • The reported experiments were made possible by the observation that pyruvate supports aerobic growth of all of the mutants tested (cya, crp, arcA, and arcB); pyruvate also supports anaerobic growth of these mutants if the alternative electron acceptor, fumarate, is provided [8].

Chemical compound and disease context of crp

  • Transport of antibiotics and metabolite analogs by systems under cyclic AMP control: positive selection of Salmonella typhimurium cya and crp mutants [9].
  • Mutants in the cyclic AMP (cAMP) control system in Salmonella typhimurium (cya = adenyl cyclase, crp = cAMP receptor protein) were partially resistant to growth inhibition by 22 antibiotics (including fosfomycin, nalidixic acid, and streptomycin) and 29 inhibitory analogs of normal bacterial fuel/carbon sources [9].

Biological context of crp

  • Salmonella typhimurium chi 4064, an attenuated delta cya delta crp mutant of S. typhimurium SR-11, was used as a carrier for the plasmid pBA31-R7 [10].
  • Inclusion of the wild-type fru operon in trans did not restore fructose-inducible beta-galactosidase expression in the fru::Mu dJ fusion mutants. cya and crp mutants exhibited reduced basal activities of all fru regulon enzymes, but inducibility was not impaired [11].
  • These suppressor mutations were traced to the crp locus and tentatively designated as acr (adenylate cyclase regulation) mutations [12].
  • This autoregulation was still observed in the crp or hns mutant background, indicating that the autogenous control is achieved by a mechanism that is independent of the cAMP-CRP and H-NS regulatory pathways [13].
  • Both strains are attenuated delta cya delta crp delta asd mutants with their Asd phenotypes complemented by the Asd+ plasmid pYA2905, which also encodes a peptide fragment of SpaA [14].

Associations of crp with chemical compounds

  • Surprisingly, fruB::Mu dJ crp or cya double mutants showed over 10-fold inducibility of the depressed beta-galactosidase activity upon addition of fructose, even though this activity in the fruB::Mu dJ fusion mutants that contained the wild-type cya and crp alleles was only slightly inducible [11].
  • Both promoters are activated by the cyclic adenosine monophosphate catabolite activator protein (cAMP/CAP) complex [15].

Other interactions of crp

  • The attenuated S. typhimurium chi 4072 delta cya delta crp delta asd mutant used in this study contains the Asd+ plasmid pYA2905 expressing a fragment of the SpaA protein [16].

Analytical, diagnostic and therapeutic context of crp

  • A stable live avirulent, genetically modified delta cya delta crp Salmonella typhimurium vaccine strain, chi 3985, was used in several vaccination strategies to evaluate its use in the control of Salmonella infection in chickens [17].


  1. Construction, characterization, and immunogenicity of an attenuated Salmonella enterica serovar typhimurium pgtE vaccine expressing fimbriae with integrated viral epitopes from the spiC promoter. Chen, H., Schifferli, D.M. Infect. Immun. (2003) [Pubmed]
  2. Safety and immunogenicity in humans of an attenuated Salmonella typhi vaccine vector strain expressing plasmid-encoded hepatitis B antigens stabilized by the Asd-balanced lethal vector system. Tacket, C.O., Kelly, S.M., Schödel, F., Losonsky, G., Nataro, J.P., Edelman, R., Levine, M.M., Curtiss, R. Infect. Immun. (1997) [Pubmed]
  3. Promoter mutation causing catabolite repression of the Salmonella typhimurium leucine operon. Gemmill, R.M., Tripp, M., Friedman, S.B., Calvo, J.M. J. Bacteriol. (1984) [Pubmed]
  4. Characterization of transmissible gastroenteritis coronavirus S protein expression products in avirulent S. typhimurium delta cya delta crp: persistence, stability and immune response in swine. Smerdou, C., Urniza, A., Curtis, R., Enjuanes, L. Vet. Microbiol. (1996) [Pubmed]
  5. Differential induction of carrier antigen-specific immunity by Salmonella typhimurium live-vaccine strains after single mucosal or intravenous immunization of BALB/c mice. Karem, K.L., Chatfield, S., Kuklin, N., Rouse, B.T. Infect. Immun. (1995) [Pubmed]
  6. Hybrid hepatitis B virus core-pre-S proteins synthesized in avirulent Salmonella typhimurium and Salmonella typhi for oral vaccination. Schödel, F., Kelly, S.M., Peterson, D.L., Milich, D.R., Curtiss, R. Infect. Immun. (1994) [Pubmed]
  7. Construction of a recombinant oral vaccine against Salmonella typhi and Salmonella typhimurium. Cao, Y., Wen, Z., Lu, D. Infect. Immun. (1992) [Pubmed]
  8. Two global regulatory systems (Crp and Arc) control the cobalamin/propanediol regulon of Salmonella typhimurium. Ailion, M., Bobik, T.A., Roth, J.R. J. Bacteriol. (1993) [Pubmed]
  9. Transport of antibiotics and metabolite analogs by systems under cyclic AMP control: positive selection of Salmonella typhimurium cya and crp mutants. Alper, M.D., Ames, B.N. J. Bacteriol. (1978) [Pubmed]
  10. Oral immunization of mice with attenuated Salmonella typhimurium containing a recombinant plasmid which codes for production of a 31-kilodalton protein of Brucella abortus. Stabel, T.J., Mayfield, J.E., Tabatabai, L.B., Wannemuehler, M.J. Infect. Immun. (1990) [Pubmed]
  11. Physiological consequences of the complete loss of phosphoryl-transfer proteins HPr and FPr of the phosphoenolpyruvate:sugar phosphotransferase system and analysis of fructose (fru) operon expression in Salmonella typhimurium. Feldheim, D.A., Chin, A.M., Nierva, C.T., Feucht, B.U., Cao, Y.W., Xu, Y.F., Sutrina, S.L., Saier, M.H. J. Bacteriol. (1990) [Pubmed]
  12. Regulatory interactions among the cya, crp and pts gene products in Salmonella typhimurium. Dobrogosz, W.J., Hall, G.W., Sherba, D.K., Silva, D.O., Harman, J.G., Melton, T. Mol. Gen. Genet. (1983) [Pubmed]
  13. Autogenous and global control of the flagellar master operon, flhD, in Salmonella typhimurium. Kutsukake, K. Mol. Gen. Genet. (1997) [Pubmed]
  14. Oral immunization with recombinant Salmonella typhimurium expressing surface protein antigen A (SpaA) of Streptococcus sobrinus: effects of the Salmonella virulence plasmid on the induction of protective and sustained humoral responses in rats. Redman, T.K., Harmon, C.C., Michalek, S.M. Vaccine (1996) [Pubmed]
  15. The mglB sequence of Salmonella typhimurium LT2; promoter analysis by gene fusions and evidence for a divergently oriented gene coding for the mgl repressor. Benner-Luger, D., Boos, W. Mol. Gen. Genet. (1988) [Pubmed]
  16. Oral immunization with recombinant Salmonella typhimurium expressing surface protein antigen A of Streptococcus sobrinus: persistence and induction of humoral responses in rats. Redman, T.K., Harmon, C.C., Michalek, S.M. Infect. Immun. (1994) [Pubmed]
  17. Development and evaluation of an experimental vaccination program using a live avirulent Salmonella typhimurium strain to protect immunized chickens against challenge with homologous and heterologous Salmonella serotypes. Hassan, J.O., Curtiss, R. Infect. Immun. (1994) [Pubmed]
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