title: An orphan sensor kinase controls quinolone signal production via MexT in Pseudomonas aeruginosa.
abstract: Pseudomonas aeruginosa employs both N-acylhomoserine lactone and 2-alkyl-4(1H)-quinolone (AQ)-mediated interbacterial signalling for the orchestration of a genome-wide gene regulatory network. Despite the many advances that have been made in understanding the target genes of quorum sensing regulation, little is known on how quorum sensing systems are influenced by environmental cues. In this study, we show that AQ production is modulated by an orphan P. aeruginosa sensor kinase. Transcriptional studies of the sensor kinase (MxtR) mutant demonstrated that an induced expression of MexT, a LysR-type transcriptional regulator, largely determined the global transcriptional profile. Thereby, overexpression of the MexT-regulated MexEF-OprN efflux pump led to a delayed expression of the AQ biosynthetic genes and of AQ-dependent virulence factors. Furthermore, we demonstrated that autophosphorylation of MxtR was inhibited by ubiquinone, the central electron carrier of respiration in in vitro experiments. Our results elucidate on a mechanism by which P. aeruginosa senses environmental conditions and adapts by controlling the production of interbacterial AQ signal molecules. A regulatory function of a sensor kinase may indicate that there is a pre-emptive role of adaptation mechanisms that are turned on under distinct environmental conditions and that are important for efficient colonization and pathogenesis.
authors.affiliation: Chronic Pseudomonas Infection Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Zaoui
authors.forename: Jörg
authors.initials: J
authors.lastname: Overhage
authors.forename: Dagmar
authors.initials: D
authors.lastname: Löns
authors.forename: Ariane
authors.initials: A
authors.lastname: Zimmermann
authors.forename: Mathias
authors.initials: M
authors.lastname: Müsken
authors.forename: Piotr
authors.initials: P
authors.lastname: Bielecki
authors.forename: Christian
authors.initials: C
authors.lastname: Pustelny
authors.forename: Tanja
authors.initials: T
authors.lastname: Becker
authors.forename: Manfred
authors.initials: M
authors.lastname: Nimtz
authors.forename: Susanne
authors.initials: S
authors.lastname: Häussler
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D006017:Glycolipids / Q000096:biosynthesis; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000235:genetics; D011710:Pyocyanine / Q000096:biosynthesis; D015363:Quinolones / Q000378:metabolism*; D053038:Quorum Sensing; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D014451:Ubiquinone / Q000378:metabolism; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D006017:Glycolipids; D015363:Quinolones; D014157:Transcription Factors; D037521:Virulence Factors; C418382:rhamnolipid; D014451:Ubiquinone; C073470:LysR protein, Bacteria; D011710:Pyocyanine; D011494:Protein Kinases