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

Summary The causative agent of Legionnaires' disease, L egionella pneumophila , employs the autoinducer compound LAI ‐1 (3‐hydroxypentadecane‐4‐one) for cell–cell communication. LAI ‐1 is produced and detected by the L qs ( L egionella quorum sensing) system, comprising the autoinducer synthase LqsA , the sensor kinases LqsS and LqsT , as well as the response regulator LqsR . L qs‐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 V ibrio 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   rsm Y and rsm Z , and negatively regulates the RNA ‐binding global regulator crs A . 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.