title: Pseudomonas aeruginosa quorum sensing molecules correlate with clinical status in cystic fibrosis.
abstract: Pseudomonas aeruginosa produces quorum sensing signal molecules that are potential biomarkers for infection.A prospective study of 60 cystic fibrosis patients with chronic P. aeruginosa, who required intravenous antibiotics for pulmonary exacerbations, was undertaken. Clinical measurements and biological samples were obtained at the start and end of the treatment period. Additional data were available for 29 of these patients when they were clinically stable.Cross-sectionally, quorum sensing signal molecules were detectable in the sputum, plasma and urine of 86%, 75% and 83% patients, respectively. They were positively correlated between the three biofluids. Positive correlations were observed for most quorum sensing signal molecules in sputum, plasma and urine, with quantitative measures of pulmonary P. aeruginosa load at the start of a pulmonary exacerbation. Plasma concentrations of 2-nonyl-4-hydroxy-quinoline (NHQ) were significantly higher at the start of a pulmonary exacerbation compared to clinical stability (p<0.01). Following the administration of systemic antibiotics, plasma 2-heptyl-4-hydroxyquinoline (p=0.02) and NHQ concentrations (p<0.01) decreased significantly.In conclusion, quorum sensing signal molecules are detectable in cystic fibrosis patients with pulmonary P. aeruginosa infection and are positively correlated with quantitative measures of P. aeruginosa. NHQ correlates with clinical status and has potential as a novel biomarker for P. aeruginosa infection.
authors.affiliation: Division of Respiratory Medicine, Clinical Sciences Building, University of Nottingham, City Hospital Campus, Nottingham, UK helen.barr@nottingham.ac.uk.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Barr
authors.affiliation: School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Halliday
authors.affiliation: School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Miguel
authors.initials: M
authors.lastname: Cámara
authors.affiliation: Centre for Analytical Bioscience, School of Pharmacy, University of Nottingham, Nottingham, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Barrett
authors.affiliation: School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Williams
authors.affiliation: Division of Respiratory Medicine, Clinical Sciences Building, University of Nottingham, City Hospital Campus, Nottingham, UK.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Forrester
authors.affiliation: Division of Respiratory Medicine, Clinical Sciences Building, University of Nottingham, City Hospital Campus, Nottingham, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Simms
authors.affiliation: Division of Child Health, Obstetrics and Gynaecology, University of Nottingham, University Hospital, Nottingham, UK.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Smyth
authors.affiliation: West Midlands Adult CF Centre, Heart of England NHS Foundation Trust, Birmingham, UK.
authors.forename: David
authors.initials: D
authors.lastname: Honeybourne
authors.affiliation: West Midlands Adult CF Centre, Heart of England NHS Foundation Trust, Birmingham, UK.
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Whitehouse
authors.affiliation: West Midlands Adult CF Centre, Heart of England NHS Foundation Trust, Birmingham, UK.
authors.forename: Edward F
authors.initials: EF
authors.lastname: Nash
authors.affiliation: Dept of Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Dewar
authors.affiliation: Dept of Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Clayton
authors.affiliation: Division of Respiratory Medicine, Clinical Sciences Building, University of Nottingham, City Hospital Campus, Nottingham, UK.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Knox
authors.affiliation: Divison of Epidemiology and Public Health, Clinical Sciences Building, University of Nottingham, Nottingham, UK.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Fogarty
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003430:Cross-Sectional Studies; D003550:Cystic Fibrosis / Q000097:blood / Q000382:microbiology* / Q000652:urine; D005260:Female; D006801:Humans; D006912:Hydroxyquinolines / Q000097:blood; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000097:blood* / Q000652:urine*; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D011804:Quinolines / Q000097:blood; D053038:Quorum Sensing; D013183:Sputum / Q000378:metabolism / Q000382:microbiology; D055815:Young Adult
chemical_list: C000609851:2-nonyl-4-hydroxyquinoline; D000900:Anti-Bacterial Agents; D015415:Biomarkers; D006912:Hydroxyquinolines; D011804:Quinolines; C049991:MY 12-62c