title: A relationship betweenPseudomonalgrowth behaviour and cystic fibrosis patient lung function identified in a metabolomic investigation.
abstract: Chronic polymicrobial lung infections in adult cystic fibrosis patients are typically dominated by high levels ofPseudomonas aeruginosa. Determining the impact ofP. aeruginosagrowth on airway secretion composition is fundamental to understanding both the behaviour of this pathogenin vivo, and its relationship with other potential colonising species. We hypothesised that the marked differences in the phenotypes of clinical isolates would be reflected in the metabolite composition of spent culture media.1H NMR spectroscopy was used to characterise the impact ofP. aeruginosagrowth on a synthetic medium as part of anin vitroCF lower airways model system. Comparisons of 15 CF clinical isolates were made and four distinct metabolomic clusters identified. Highly significant relationships betweenP. aeruginosaisolate cluster membership and both patient lung function (FEV1) and spent culture pH were identified. This link between clinical isolate growth behaviour and FEV1indicates characterisation ofP. aeruginosagrowth may find application in predicting patient lung function while the significant divergence in metabolite production and consumption observed between CF clinical isolates suggests dominant isolate characteristics have the potential to play both a selective role in microbiota composition and influence pseudomonal behaviourin vivo.
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
authors.forename: Justyna
authors.initials: J
authors.lastname: Kozlowska
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
authors.forename: Damian W
authors.initials: DW
authors.lastname: Rivett
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
authors.forename: Louic S
authors.initials: LS
authors.lastname: Vermeer
authors.affiliation: Cystic Fibrosis Unit, Southampton University Hospitals NHS Trust, Southampton, SO16 6YD, UK.
authors.forename: Mary P
authors.initials: MP
authors.lastname: Carroll
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bruce
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
authors.forename: A James
authors.initials: AJ
authors.lastname: Mason
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
authors.forename: Geraint B
authors.initials: GB
authors.lastname: Rogers
keywords: NMR; Pseudomonal; cystic fibrosis; lung function