title: The Legionella pneumophila orphan sensor kinase LqsT regulates competence and pathogen-host interactions as a component of the LAI-1 circuit.
abstract: Legionella pneumophila is an amoeba-resistant opportunistic pathogen that performs cell-cell communication through the signalling molecule 3-hydroxypentadecane-4-one (LAI-1, Legionella autoinducer-1). The lqs (Legionella quorum sensing) gene cluster encodes the LAI-1 autoinducer synthase LqsA, the cognate sensor kinase LqsS and the response regulator LqsR. Here we show that the Lqs system includes an 'orphan' homologue of LqsS termed LqsT. Compared with wild-type L. pneumophila, strains lacking lqsT or both lqsS and lqsT show increased salt resistance, greatly enhanced natural competence for DNA acquisition and impaired uptake by phagocytes. Sensitive novel single round growth assays and competition experiments using Acanthamoeba castellanii revealed that ΔlqsT and ΔlqsS-ΔlqsT, as well as ΔlqsA and other lqs mutant strains are impaired for intracellular growth and cannot compete against wild-type bacteria upon co-infection. In contrast to the ΔlqsS strain, ΔlqsT does not produce extracellular filaments. The phenotypes of the ΔlqsS-ΔlqsT strain are partially complemented by either lqsT or lqsS, but are not reversed by overexpression of lqsA, suggesting that LqsT and LqsS are the sole LAI-1-responsive sensor kinases in L. pneumophila. In agreement with the different phenotypes of the ΔlqsT and ΔlqsS strains, lqsT and lqsS are differentially expressed in the post-exponential growth phase, and transcriptome studies indicated that 90% of the genes, which are downregulated in absence of lqsT, are upregulated in absence of lqsS. Reciprocally regulated genes encode components of a 133 kb genomic 'fitness island' or translocated effector proteins implicated in virulence. Together, these results reveal a unique organization of the L. pneumophila Lqs system comprising two partially antagonistic LAI-1-responsive sensor kinases, LqsT and LqsS, which regulate distinct pools of genes implicated in pathogen-host cell interactions, competence, expression of a genomic island or production of extracellular filaments.
authors.affiliation: Max von Pettenkofer Institute, Ludwig-Maximilians University, Pettenkoferstraße 9a, 80336 Munich, Germany.
authors.forename: Aline
authors.initials: A
authors.lastname: Kessler
authors.forename: Ursula
authors.initials: U
authors.lastname: Schell
authors.forename: Tobias
authors.initials: T
authors.lastname: Sahr
authors.forename: André
authors.initials: A
authors.lastname: Tiaden
authors.forename: Christopher
authors.initials: C
authors.lastname: Harrison
authors.forename: Carmen
authors.initials: C
authors.lastname: Buchrieser
authors.forename: Hubert
authors.initials: H
authors.lastname: Hilbi
mesh_terms: D048248:Acanthamoeba castellanii / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D061269:DNA Transformation Competence / Q000235:genetics*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D054884:Host-Pathogen Interactions / Q000502:physiology*; D016952:Legionella pneumophila / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism*; D053038:Quorum Sensing / Q000235:genetics; D012492:Salts / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; C085427:LuxI protein, Bacteria; D012492:Salts; D014157:Transcription Factors; D010770:Phosphotransferases