title: Diversity of metabolic profiles of cystic fibrosis Pseudomonas aeruginosa during the early stages of lung infection.
abstract: Pseudomonas aeruginosa is the dominant pathogen infecting the airways of cystic fibrosis (CF) patients. During the intermittent colonization phase, P. aeruginosa resembles environmental strains but later evolves to the chronic adapted phenotype characterized by resistance to antibiotics and mutations in the global regulator genes mucA, lasR and rpoN. Our aim was to understand the metabolic changes occurring over time and between niches of the CF airways. By applying Phenotype MicroArrays, we investigated changes in the carbon and nitrogen catabolism of subsequently clonally related mucoid and non-mucoid (NM) lung and sinus P. aeruginosa isolates from 10 CF patients (five intermittently colonized/five chronically infected). We found the most pronounced catabolic changes for the early/late NM isolate comparisons, with respiratory reduction seen for all chronically infecting isolates and two intermittently colonizing isolates. Fewer differences were observed between sinus and lung isolates, showing a higher degree of isolate similarity between these two niches. Modest respiratory changes were seen for the early isolate/PAO1 comparisons, indicating colonization with environmental isolates. Assignment of metabolic pathways via the KEGG database showed a prevalence of substrates involved in the metabolism of Ala, Asp and Glu, d-Ala, and Arg and Pro. In conclusion, extensive heterogeneity in the metabolic profiles of the P. aeruginosa isolates was observed from the initial stages of the infection, showing a rapid diversification of the bacteria in the heterogeneous environment of the lung. Metabolic reduction seems to be a common trait and therefore an adaptive phenotype, though it can be reached via multiple metabolic pathways.
authors: 1​ Department of Immunology and Microbiology, Costerton Biofilm Center, University of Copenhagen, Denmark.
authors: Karin Meinike
authors: KM
authors: Jørgensen
authors: 2​ Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
authors: Tina
authors: T
authors: Wassermann
authors: 2​ Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark 3​ The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Hørsholm, Denmark.
authors: Helle Krogh
authors: HK
authors: Johansen
authors: 4​ Department of Informatics and Mathematical Modelling, Technical University of Denmark, Denmark.
authors: Lasse Engbo
authors: LE
authors: Christiansen
authors: 3​ The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Hørsholm, Denmark 5​ Center for Systems Biology, Technical University of Denmark, Denmark.
authors: Søren
authors: S
authors: Molin
authors: 1​ Department of Immunology and Microbiology, Costerton Biofilm Center, University of Copenhagen, Denmark 2​ Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
authors: Niels
authors: N
authors: Høiby
authors: 1​ Department of Immunology and Microbiology, Costerton Biofilm Center, University of Copenhagen, Denmark.
authors: Oana
authors: O
authors: Ciofu
mesh_terms: D002244:Carbon / Q000378:metabolism; D003550:Cystic Fibrosis / Q000150:complications*; D003718:Denmark; D006801:Humans; D008137:Longitudinal Studies; D008168:Lung / Q000382:microbiology*; D055442:Metabolome; D009584:Nitrogen / Q000378:metabolism; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification / Q000378:metabolism*; D012141:Respiratory Tract Infections / Q000382:microbiology*
chemical_list: D002244:Carbon; D009584:Nitrogen