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Mol Microbiol. 2016 Feb;99(4):778-93. doi: 10.1111/mmi.13265. Epub 2015 Nov 27.

The α-hydroxyketone LAI-1 regulates motility, Lqs-dependent phosphorylation signalling and gene expression of Legionella pneumophila.

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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.
Institut Pasteur, Unité de Biologie des Bactéries Intracellulaires, Paris, France.
CNRS UMR 3525, 28 Rue du Dr Roux, 75724, Paris, France.
Department of Chemistry, Ludwig-Maximilians University, Butenandtstrasse 5-13, Building F, 81377, Munich, Germany.
Chemical Biology Center (KBC), Institute of Chemistry, Umeå University, S-90187, Umeå, Sweden.


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.

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