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Gene Review

vfr  -  cAMP-regulatory protein

Pseudomonas aeruginosa PAO1

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Disease relevance of vfr

  • Deletion and insertion mutants of fimL frequently revert to wild-type phenotypes suggesting that an extragenic suppressor mutation is able to overcome the loss of fimL. vfr transcription and production, as well as cAMP levels, are elevated in these revertants, while Pseudomonas quinolone signal (PQS) production is reduced [1].
  • In Escherichia coli, when vfr was overexpressed from a phage T7 promoter, a protein with an apparent molecular mass of 28.5 kDa was produced [2].

High impact information on vfr

  • Based on the enumeration of bacteria in lungs, livers, and spleens, as well as the assessment of mouse lung pathology, mutations in the cyaB and vfr genes resulted in a more significantly attenuated phenotype than mutations in cyaA [3].
  • By contrast, in an rpoN mutant, the expression of the gacA global regulatory gene was significantly increased during the entire growth cycle, whereas another global regulatory gene, vfr, was downregulated at high cell densities [4].
  • Further analysis showed that the stable twitching-defective variants of lasI and rhlI mutants had arisen as a consequence of secondary mutations in vfr and algR, respectively, both of which encode key regulators affecting a variety of phenotypes, including twitching motility [5].
  • This allele (VfrDeltaEQERS) was capable of restoring elastase and pyocyanin production to wild-type levels in vfr-null mutants but not their defects in twitching motility [6].
  • We also identified reduced-twitching variants of quorum-sensing mutants (PAK lasI::Tc) with a spontaneous deletion in vfr (S. A. Beatson, C. B. Whitchurch, A. B. T. Semmler, and J. S. Mattick, J. Bacteriol., 184:3598-3604, 2002), the net result of which was the loss of five residues (EQERS) from the putative cAMP-binding pocket of Vfr [6].

Chemical compound and disease context of vfr

  • The vfr gene product, required for Pseudomonas aeruginosa exotoxin A and protease production, belongs to the cyclic AMP receptor protein family [2].

Biological context of vfr


Associations of vfr with chemical compounds

  • The cloned vfr gene restored Vfr-dependent production of exotoxin A and protease in the PA103 orfX'-vfr-trpC' deletion mutant, suggesting that ORFX is not required for Vfr production or activity [7].

Other interactions of vfr


Analytical, diagnostic and therapeutic context of vfr

  • Proteins from stationary phase culture supernatants were collected from wild-type and P. aeruginosa PAO1 mutants deficient in one or more of the lasRI, rhlRI and vfr genes and analysed using two-dimensional gel electrophoresis [10].


  1. Pseudomonas aeruginosa fimL regulates multiple virulence functions by intersecting with Vfr-modulated pathways. Whitchurch, C.B., Beatson, S.A., Comolli, J.C., Jakobsen, T., Sargent, J.L., Bertrand, J.J., West, J., Klausen, M., Waite, L.L., Kang, P.J., Tolker-Nielsen, T., Mattick, J.S., Engel, J.N. Mol. Microbiol. (2005) [Pubmed]
  2. The vfr gene product, required for Pseudomonas aeruginosa exotoxin A and protease production, belongs to the cyclic AMP receptor protein family. West, S.E., Sample, A.K., Runyen-Janecky, L.J. J. Bacteriol. (1994) [Pubmed]
  3. An adenylate cyclase-controlled signaling network regulates Pseudomonas aeruginosa virulence in a mouse model of acute pneumonia. Smith, R.S., Wolfgang, M.C., Lory, S. Infect. Immun. (2004) [Pubmed]
  4. Negative control of quorum sensing by RpoN (sigma54) in Pseudomonas aeruginosa PAO1. Heurlier, K., Dénervaud, V., Pessi, G., Reimmann, C., Haas, D. J. Bacteriol. (2003) [Pubmed]
  5. Quorum sensing is not required for twitching motility in Pseudomonas aeruginosa. Beatson, S.A., Whitchurch, C.B., Semmler, A.B., Mattick, J.S. J. Bacteriol. (2002) [Pubmed]
  6. Differential regulation of twitching motility and elastase production by Vfr in Pseudomonas aeruginosa. Beatson, S.A., Whitchurch, C.B., Sargent, J.L., Levesque, R.C., Mattick, J.S. J. Bacteriol. (2002) [Pubmed]
  7. A divergently transcribed open reading frame is located upstream of the Pseudomonas aeruginosa vfr gene, a homolog of Escherichia coli crp. Runyen-Janecky, L.J., Sample, A.K., Maleniak, T.C., West, S.E. J. Bacteriol. (1997) [Pubmed]
  8. Effect of vfr mutation on global gene expression and catabolite repression control of Pseudomonas aeruginosa. Suh, S.J., Runyen-Janecky, L.J., Maleniak, T.C., Hager, P., MacGregor, C.H., Zielinski-Mozny, N.A., Phibbs, P.V., West, S.E. Microbiology (Reading, Engl.) (2002) [Pubmed]
  9. Osmoprotectant-dependent expression of plcH, encoding the hemolytic phospholipase C, is subject to novel catabolite repression control in Pseudomonas aeruginosa PAO1. Sage, A.E., Vasil, M.L. J. Bacteriol. (1997) [Pubmed]
  10. Proteome analysis of extracellular proteins regulated by the las and rhl quorum sensing systems in Pseudomonas aeruginosa PAO1. Nouwens, A.S., Beatson, S.A., Whitchurch, C.B., Walsh, B.J., Schweizer, H.P., Mattick, J.S., Cordwell, S.J. Microbiology (Reading, Engl.) (2003) [Pubmed]
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