Abstract
The ubiquitous Gram-negative bacterium Legionella pneumophila parasitizes 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. pneumophila employs the Lqs (Legionella quorum 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 (Legionella autoinducer-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 by L. pneumophila and sensed by the bacteria as well as by eukaryotic cells plays a major role in pathogen-host cell interactions.
Highlights
Reviewed by: Mika Tapio Tarkka, Helmholtz Centre for Environmental Research (HZ), Germany Xavier Charpentier, Centre de Recherche en Infectiologie – INSERM U1111, France
The low molecular weight compound Legionella autoinducer-1 (LAI-1) produced by L. pneumophila and sensed by the bacteria as well as by eukaryotic cells plays a major role in pathogen-host cell interactions
Host cell-produced inter-kingdom signaling molecules include adrenergic compounds, which are detected by a number of bacterial genera through the QseBC two-component system (TCS; Kendall and Sperandio, 2016)
Summary
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 (Legionella autoinducer-1, 3-hydroxypentadecane-4-one). The low molecular weight compound LAI-1 produced by L. pneumophila and sensed by the bacteria as well as by eukaryotic cells plays a major role in pathogen-host cell interactions. Prominent examples of low molecular weight compounds promoting quorum sensing of Gram-negative bacteria include N-acyl-homoserine lactone (HSL) autoinducers, diffusible signal factor (DSF), autoinducer-2 (AI-2) and its precursor 4,5-dihydroxy-2,3-pentanedione (DPD), 2-heptyl-3-hydroxy-4-quinolone (PQS), as well as dialkylresorcinol (DAR) and α-hydroxyketone (AHK) molecules (Papenfort and Bassler, 2016)
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