title: The α-hydroxyketone LAI-1 regulates motility, Lqs-dependent phosphorylation signalling and gene expression of Legionella pneumophila.
abstract: The causative agent of Legionnaires' disease, Legionella pneumophila, employs the autoinducer compound LAI-1 (3-hydroxypentadecane-4-one) for cell-cell communication. LAI-1 is produced and detected by the Lqs (Legionella quorum sensing) system, comprising the autoinducer synthase LqsA, the sensor kinases LqsS and LqsT, as well as the response regulator LqsR. Lqs-regulated processes include pathogen-host interactions, production of extracellular filaments and natural competence for DNA uptake. Here we show that synthetic LAI-1 promotes the motility of L. pneumophila by signalling through LqsS/LqsT and LqsR. Upon addition of LAI-1, autophosphorylation of LqsS/LqsT by [γ-(32) P]-ATP was inhibited in a dose-dependent manner. In contrast, the Vibrio cholerae autoinducer CAI-1 (3-hydroxytridecane-4-one) promoted the phosphorylation of LqsS (but not LqsT). LAI-1 did neither affect the stability of phospho-LqsS or phospho-LqsT, nor the dephosphorylation by LqsR. Transcriptome analysis of L. pneumophila treated with LAI-1 revealed that the compound positively regulates a number of genes, including the non-coding RNAs rsmY and rsmZ, and negatively regulates the RNA-binding global regulator crsA. Accordingly, LAI-1 controls the switch from the replicative to the transmissive growth phase of L. pneumophila. In summary, the findings indicate that LAI-1 regulates motility and the biphasic life style of L. pneumophila through LqsS- and LqsT-dependent phosphorylation signalling.
authors.affiliation: Max von Pettenkofer Institute, Ludwig-Maximilians University, Pettenkoferstraße 9a, 80336, Munich, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Schell
authors.affiliation: Max von Pettenkofer Institute, Ludwig-Maximilians University, Pettenkoferstraße 9a, 80336, Munich, Germany.|Institute of Medical Microbiology, University of Zürich, Gloriastrasse 30/32, 8006, Zürich, Switzerland.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Simon
authors.affiliation: Institut Pasteur, Unité de Biologie des Bactéries Intracellulaires, Paris, France.|CNRS UMR 3525, 28 Rue du Dr Roux, 75724, Paris, France.
authors.forename: Tobias
authors.initials: T
authors.lastname: Sahr
authors.affiliation: Department of Chemistry, Ludwig-Maximilians University, Butenandtstrasse 5-13, Building F, 81377, Munich, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Hager
authors.affiliation: Chemical Biology Center (KBC), Institute of Chemistry, Umeå University, S-90187, Umeå, Sweden.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Albers
authors.affiliation: Max von Pettenkofer Institute, Ludwig-Maximilians University, Pettenkoferstraße 9a, 80336, Munich, Germany.
authors.forename: Aline
authors.initials: A
authors.lastname: Kessler
authors.affiliation: Department of Chemistry, Ludwig-Maximilians University, Butenandtstrasse 5-13, Building F, 81377, Munich, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Fahrnbauer
authors.affiliation: Department of Chemistry, Ludwig-Maximilians University, Butenandtstrasse 5-13, Building F, 81377, Munich, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Trauner
authors.affiliation: Chemical Biology Center (KBC), Institute of Chemistry, Umeå University, S-90187, Umeå, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Hedberg
authors.affiliation: Institut Pasteur, Unité de Biologie des Bactéries Intracellulaires, Paris, France.|CNRS UMR 3525, 28 Rue du Dr Roux, 75724, Paris, France.
authors.forename: Carmen
authors.initials: C
authors.lastname: Buchrieser
authors.affiliation: Max von Pettenkofer Institute, Ludwig-Maximilians University, Pettenkoferstraße 9a, 80336, Munich, Germany.|Institute of Medical Microbiology, University of Zürich, Gloriastrasse 30/32, 8006, Zürich, Switzerland.
authors.forename: Hubert
authors.initials: H
authors.lastname: Hilbi
mesh_terms: D000473:Alkanes / Q000378:metabolism* / Q000494:pharmacology; D002465:Cell Movement; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D054884:Host-Pathogen Interactions; D007659:Ketones / Q000378:metabolism* / Q000494:pharmacology; D016952:Legionella pneumophila / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D009068:Movement; D010766:Phosphorylation; D053038:Quorum Sensing; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014734:Vibrio cholerae / Q000235:genetics
chemical_list: C000611984:3-hydroxypentadecane-4-one; C525620:3-hydroxytridecan-4-one; D000473:Alkanes; D007659:Ketones; D014157:Transcription Factors