title: Intra-Species and Inter-Kingdom Signaling ofLegionella pneumophila.
abstract: The ubiquitous Gram-negative bacteriumLegionella pneumophilaparasitizes environ mental amoebae and, upon inhalation, replicates in alveolar macrophages, thus causing a life-threatening pneumonia called "Legionnaires' disease." The opportunistic pathogen employs a bi-phasic life cycle, alternating between a replicative, non-virulent phase and a stationary, transmissive/virulent phase.L. pneumophilaemploys the Lqs (Legionellaquorum sensing) system as a major regulator of the growth phase switch. The Lqs system comprises the autoinducer synthase LqsA, the homologous sensor kinases LqsS and LqsT, as well as a prototypic response regulator termed LqsR. These components produce, detect, and respond to the α-hydroxyketone signaling molecule LAI-1 (Legionellaautoinducer-1, 3-hydroxypentadecane-4-one). LAI-1-mediated signal transduction through the sensor kinases converges on LqsR, which dimerizes upon phosphorylation. The Lqs system regulates the bacterial growth phase switch, pathogen-host cell interactions, motility, natural competence, filament production, and expression of a chromosomal "fitness island." Yet, LAI-1 not only mediates bacterial intra-species signaling, but also modulates the motility of eukaryotic cells through the small GTPase Cdc42 and thus promotes inter-kingdom signaling. Taken together, the low molecular weight compound LAI-1 produced byL. pneumophilaand sensed by the bacteria as well as by eukaryotic cells plays a major role in pathogen-host cell interactions.
authors.affiliation: Department of Medicine, Institute of Medical Microbiology, University of Zürich Zürich, Switzerland.
authors.forename: Ramon
authors.initials: R
authors.lastname: Hochstrasser
authors.affiliation: Department of Medicine, Institute of Medical Microbiology, University of Zürich Zürich, Switzerland.
authors.forename: Hubert
authors.initials: H
authors.lastname: Hilbi
keywords: Dictyostelium; Legionella; amoeba; autoinducer; bacterial pathogenesis; cell–cell communication; macrophage; phospho-transfer; quorum sensing; response regulator; sensor kinase; small molecule signaling; α-hydroxyketone