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

Summary 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‐32P]‐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. The environmental bacterium Legionella pneumophila causes a severe pneumonia termed Legionnaires′ disease. For cell‐to‐cell communication, the pathogen uses the small signaling molecule LAI‐1, which is produced and detected by the Lqs (Legionella quorum sensing) system. We show that synthetic LAI‐1 is recognized by the membrane‐bound sensor kinases LqsS and LqsT, which transfer the phosphorylation signal to the response regulator LqsR. Thus, LAI‐1 regulates gene expression and motility of L. pneumophila through Lqs‐dependent signal transduction.