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

TitleThe Legionella autoinducer synthase LqsA produces an alpha-hydroxyketone signaling molecule.
Publication TypeJournal Article
Year of Publication2008
AuthorsSpirig, T, Tiaden, A, Kiefer, P, Buchrieser, C, Vorholt, JA, Hilbi, H
JournalJ Biol Chem
Volume283
Issue26
Pagination18113-23
Date Published2008 Jun 27
ISSN0021-9258
KeywordsBacterial Proteins, Binding Sites, Gene Expression Regulation, Bacterial, Genetic Complementation Test, Ketones, Legionella pneumophila, Mass Spectrometry, Models, Biological, Models, Chemical, Phenotype, Protein Binding, Protein Kinases, Pyridoxal Phosphate, Signal Transduction, Time Factors, Virulence
Abstract

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.

DOI10.1074/jbc.M801929200
Alternate JournalJ. Biol. Chem.