title: Regulation of Pseudomonas quinolone signal synthesis in Pseudomonas aeruginosa.
abstract: Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic lung infections in cystic fibrosis patients and is a major source of nosocomial infections. This bacterium controls many virulence factors by using two quorum-sensing systems, las and rhl. The las system is composed of the LasR regulator protein and its cell-to-cell signal, N-(3-oxododecanoyl) homoserine lactone, and the rhl system is composed of RhlR and the signal N-butyryl homoserine lactone. A third intercellular signal, the Pseudomonas quinolone signal (PQS; 2-heptyl-3-hydroxy-4-quinolone), also regulates numerous virulence factors. PQS synthesis requires the expression of multiple operons, one of which is pqsABCDE. Previous experiments showed that the transcription of this operon, and therefore PQS production, is negatively regulated by the rhl quorum-sensing system and positively regulated by the las quorum-sensing system and PqsR (also known as MvfR), a LysR-type transcriptional regulator protein. With the use of DNA mobility shift assays and beta-galactosidase reporter fusions, we have studied the regulation of pqsR and its relationship to pqsA, lasR, and rhlR. We show that PqsR binds the promoter of pqsA and that this binding increases dramatically in the presence of PQS, implying that PQS acts as a coinducer for PqsR. We have also mapped the transcriptional start site for pqsR and found that the transcription of pqsR is positively regulated by lasR and negatively regulated by rhlR. These results suggest that a regulatory chain occurs where pqsR is under the control of LasR and RhlR and where PqsR in turn controls pqsABCDE, which is required for the production of PQS.
authors.affiliation: Department of Microbiology and Immunology, East Carolina University School of Medicine, BT 132, 600 Moye Blvd., Greenville, NC 27834, USA.
authors.forename: Dana S
authors.initials: DS
authors.lastname: Wade
authors.forename: M Worth
authors.initials: MW
authors.lastname: Calfee
authors.forename: Edson R
authors.initials: ER
authors.lastname: Rocha
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ling
authors.forename: Elana
authors.initials: E
authors.lastname: Engstrom
authors.forename: James P
authors.initials: JP
authors.lastname: Coleman
authors.forename: Everett C
authors.initials: EC
authors.lastname: Pesci
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009876:Operon; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D015363:Quinolones / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism
chemical_list: C407944:2-heptyl-3-hydroxy-4-quinolone; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C080365:LasR protein, Pseudomonas aeruginosa; D015363:Quinolones; C086515:RhlR protein, Pseudomonas aeruginosa; D015534:Trans-Activators