The Legionella autoinducer synthase LqsA produces an alpha-hydroxyketone signaling molecule

J Biol Chem. 2008 Jun 27;283(26):18113-23. doi: 10.1074/jbc.M801929200. Epub 2008 Apr 14.


The opportunistic pathogen Legionella pneumophila replicates in human lung macrophages and in free-living amoebae. To accommodate the transfer between host cells, L. pneumophila switches from a replicative to a transmissive phase. L. pneumophila harbors a gene cluster homologous to the Vibrio cholerae cqsAS quorum sensing system, encoding a putative autoinducer synthase (lqsA) and a sensor kinase (lqsS), which flank a response regulator (lqsR). LqsR is an element of the L. pneumophila virulence regulatory network, which promotes pathogen-host cell interactions and inhibits entry into the replicative growth phase. Here, we show that lqsA functionally complements a V. cholerae cqsA autoinducer synthase deletion mutant and, upon expression in L. pneumophila or Escherichia coli, produces the diffusible signaling molecule LAI-1 (Legionella autoinducer-1). LAI-1 is distinct from CAI-1 (Cholerae autoinducer-1) and was identified as 3-hydroxypentadecan-4-one using liquid chromatography coupled to high resolution tandem mass spectrometry. The activity of both LqsA and CqsA was abolished upon mutation of a conserved lysine, and covalent binding of the cofactor pyridoxal 5'-phosphate to this lysine was confirmed by mass spectrometry. Thus, LqsA and CqsA belong to a family of pyridoxal 5'-phosphate-dependent autoinducer synthases, which produce the alpha-hydroxyketone signaling molecules LAI-1 and CAI-1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Binding Sites
  • Gene Expression Regulation, Bacterial
  • Genetic Complementation Test
  • Ketones / chemistry*
  • Legionella pneumophila / metabolism*
  • Mass Spectrometry
  • Models, Biological
  • Models, Chemical
  • Phenotype
  • Protein Binding
  • Protein Kinases / chemistry
  • Protein Kinases / physiology*
  • Pyridoxal Phosphate / chemistry
  • Signal Transduction
  • Time Factors
  • Virulence


  • Bacterial Proteins
  • Ketones
  • Pyridoxal Phosphate
  • Protein Kinases