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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Gene Review

cyaA  -  bifunctional hemolysin-adenylate cyclase

Bordetella pertussis Tohama I

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Disease relevance of cyaA


High impact information on cyaA

  • The Bordetella pertussis adenylate cyclase (cya) operon is composed of four open reading frames, cyaA, B, D and E (Glaser et al., 1988, EMBO J., 7, 3997-4004) [4].
  • The cyaA gene encodes a virulence factor, cyclolysin, a bifunctional protein exhibiting both adenylate cyclase and haemolytic activities while the cyaB, D and E gene products are necessary for cyclolysin transport [4].
  • The gene encoding the AC toxin (cyaA) is expressed as part of an operon that includes genes required for secretion or activation of the toxin [2].
  • Therefore, to clarify the role of individual toxin functions in the virulence of B. pertussis, we have used site-directed or deletion mutagenesis and genetic recombination to specifically target the cyaA gene of B. pertussis to produce mutants that lack only the AC or HLY activity of this toxin [2].
  • We show that adenylate cyclase synthesized as a 200-kilodalton protein is the product of the cyaA gene and that various virulent Bordetella species secrete this high-molecular-weight polypeptide without apparent proteolytic processing [5].

Biological context of cyaA

  • Because of this genetic organization, it is difficult to create B. pertussis mutants of cyaA that are ablations of a single enzyme function by conventional means, such as transposon mutagenesis [2].
  • We show that the BvgA binding sites within the bvgp(1) and cyaA promoters consist of inverted repeats and suggest that inverted-repeat motifs may represent the recognition elements for DNA-BvgA interaction [6].
  • A 400-bp region in the promoter upstream region of the cyaA gene, encoding the toxin, has been defined as the target of transcriptional activation [7].

Other interactions of cyaA

  • Bordetella pertussis produces a cell-invasive adenylate cyclase toxin which is synthesised from the cyaA gene as an inactive protoxin that is post-translationally activated by the product of the cyaC gene [1].

Analytical, diagnostic and therapeutic context of cyaA


  1. Adjuvant and protective properties of native and recombinant Bordetella pertussis adenylate cyclase toxin preparations in mice. Hormozi, K., Parton, R., Coote, J. FEMS Immunol. Med. Microbiol. (1999) [Pubmed]
  2. Targeted mutations that ablate either the adenylate cyclase or hemolysin function of the bifunctional cyaA toxin of Bordetella pertussis abolish virulence. Gross, M.K., Au, D.C., Smith, A.L., Storm, D.R. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  3. Identification of new secreted effectors in Salmonella enterica serovar Typhimurium. Geddes, K., Worley, M., Niemann, G., Heffron, F. Infect. Immun. (2005) [Pubmed]
  4. Virulence dependent and independent regulation of the Bordetella pertussis cya operon. Laoide, B.M., Ullmann, A. EMBO J. (1990) [Pubmed]
  5. Synthesis and secretion of Bordetella pertussis adenylate cyclase as a 200-kilodalton protein. Bellalou, J., Ladant, D., Sakamoto, H. Infect. Immun. (1990) [Pubmed]
  6. Characterization of DNA binding sites for the BvgA protein of Bordetella pertussis. Karimova, G., Ullmann, A. J. Bacteriol. (1997) [Pubmed]
  7. Bordetella pertussis adenylate cyclase: a toxin with multiple talents. Goyard, S., Sebo, P., D'Andria, O., Ladant, D., Ullmann, A. Zentralbl. Bakteriol. (1993) [Pubmed]
  8. Identification of Bordetella pertussis in nasopharyngeal swabs by PCR amplification of a region of the adenylate cyclase gene. Douglas, E., Coote, J.G., Parton, R., McPheat, W. J. Med. Microbiol. (1993) [Pubmed]
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