Intra-Species and Inter-Kingdom Signaling of Legionella pneumophila

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.

The Life Cycle of L. pneumophila: Cellular Differentiation Is Linked to Virulence and Metabolism

“…It is likely that a regulatory switch between at least two sets of effectors occurs: one set of effectors, activated by PmrA/B and expressed in the replicative state and the second group of effectors which is regulated by the LetA/S TCS upon entry into the transmissive phase of L. pneumophila . Another player in this complex regulatory network, is the TCS LqsRS ( Legionella quorum sensing), whose role in the regulation of gene expression during the transmissive phase has been extensively studied (Hochstrasser and Hilbi, 2017 ). Importantly, the production of LqsR is regulated at the post-transcriptional level by the global repressor CsrA (Sahr et al, 2009 , 2017 ).…”

The pleiotropic Legionella transcription factor LvbR links the Lqs and c‐di‐GMP regulatory networks to control biofilm architecture and virulence

“…The phase switch is controlled by a complex regulatory network, including the two‐component system LetAS (Segal, ), the RNA‐binding global regulator CsrA (carbon storage regulator A) (Sahr et al ., ) and the Lqs system (Fig. A) (Hochstrasser and Hilbi, ). Components of the Lqs system are encoded in a genomic cluster ( lqsA–lqsR–hdeD–lqsS ) (Tiaden et al ., ; Tiaden and Hilbi, ) as well as by an orphan gene ( lqsT ) (Kessler et al ., ), all expressed from individual promoters (Sahr et al ., ).…”

Acanthamoeba and Dictyostelium as Cellular Models for Legionella Infection

“…Environmental microorganisms commonly colonize and form communities called biofilms, which comprise large numbers of prokaryotic and eukaryotic cells associating via adhesion molecules and secreted compounds. Biofilms are ubiquitously found in the environment and contain a plethora of bacterial species, many of which communicate via low molecular weight signaling molecules in a process termed quorum sensing (Hall-Stoodley et al, 2004 ; Hochstrasser and Hilbi, 2017 ). These biofilms are attacked (“grazed”) by predatory amoebae and ciliates, resulting in a reduction in the bacterial population.…”

“…The completed genome sequence of D. discoideum , a remarkable repertoire of molecular genetic tools, and the intrinsic biological features of the amoebae allow to study many fundamental cellular processes (Bergmann and Steinert, 2015 ; Bretschneider et al, 2016 ; Hochstrasser and Hilbi, 2017 ). In the haploid amoeba D. discoideum non-essential genes can be easily disrupted or replaced by homologous recombination.…”