Coordinate regulation of bacterial virulence genes by a novel adenylate cyclase-dependent signaling pathway

Dev Cell. 2003 Feb;4(2):253-63. doi: 10.1016/s1534-5807(03)00019-4.


Type III secretion systems (TTSSs) are utilized by numerous bacterial pathogens to inject effector proteins directly into host cells. Using a whole-genome microarray, we investigated the conditions and regulatory factors that control the expression of the Pseudomonas aeruginosa TTSS. The transcriptional response of known TTSS genes indicates a hierarchical pattern of expression in which a set of secretion apparatus and regulatory genes is constitutively expressed. Further analysis of genes coordinately regulated with those encoding the TTSS led to the identification of a signaling pathway that originates from a membrane-associated adenylate cyclase and controls TTSS gene expression. Transcriptome analysis of mutants lacking the ability to synthesize cAMP or the cAMP binding protein Vfr implicated this pathway in the global regulation of host-directed virulence determinants, including the TTSS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Animals
  • CHO Cells
  • Carrier Proteins
  • Cricetinae
  • Cyclic AMP / metabolism
  • Cyclic AMP Receptor Protein / metabolism
  • DNA Primers / chemistry
  • Gene Expression Profiling
  • Genes, Bacterial / physiology*
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Protein Biosynthesis / drug effects
  • Pseudomonas aeruginosa / enzymology
  • Pseudomonas aeruginosa / genetics*
  • Pseudomonas aeruginosa / pathogenicity*
  • Signal Transduction*
  • Virulence / genetics


  • Carrier Proteins
  • Cyclic AMP Receptor Protein
  • DNA Primers
  • Cyclic AMP
  • Adenylyl Cyclases