Gene regulation by alpha-hydroxyketone-mediated signaling in Legionella pneumophila

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Bacteria regulate gene expression by responding to environmental cues and by producing endogenous signaling molecules termed autoinducers. The pathogenic bacterium Legionella pneumophila harbors the lqs (Legionella quorum sensing) gene cluster, which encodes the autoinducer synthase LqsA, the putative cognate sensor kinase LqsS and the novel response regulator LqsR. LqsA is a pyridoxal-5´-phosphate-dependent enzyme and synthesizes LAI-1 (Legionella autoinducer-1, 3-hydroxypentadecane-4-one), a member of the α-hydroxyketone signaling molecule family. Functional studies and transcriptome analysis revealed that the lqsA, lqsS and lqsR genes regulate L. pneumophila-host cell interactions, extracellular filaments and a genomic “fitness island”. The aims of this project are a detailed molecular analysis of α-hydroxyketone-mediated gene regulation in L. pneumophila using biochemical, genetic and cellular microbial approaches. Specifically, the following topics are the focus of this application: (i) α-hydroxyketone-mediated signal transduction by the homologous sensor kinases LqsS and LqsT, (ii) function and structure of the response regulator LqsR, and (iii) endogenous production of LAI-1 and extracellular filaments.