title: Pseudomonas aeruginosa population diversity and turnover in cystic fibrosis chronic infections.
abstract: BACKGROUND
  Pseudomonas aeruginosa isolates from chronic cystic fibrosis lung infections display multiple phenotypes indicating extensive population diversity.
  
  
  OBJECTIVE
  We aimed to examine how such diversity is distributed within and between patients, and to study the dynamics of single-strain phenotypic diversity in multiple patients through time.
  
  
  METHODS
  Sets of 40 P. aeruginosa isolates per sputum samples were analyzed for a series of phenotypic and genotypic characteristics. Population differentiation between patients, between samples within patients, and between isolates within samples was analyzed.
  
  
  RESULTS
  We characterized 15 traits for a total of 1,720 isolates of an important and widely disseminated epidemic strain of P. aeruginosa from 10 chronically infected patients with cystic fibrosis multiply sampled during 2009. Overall, 43 sputum samples were analyzed and 398 haplotypes of the Liverpool Epidemic Strain were identified. The majority of phenotypic diversity occurred within patients. Such diversity is highly dynamic, displaying rapid turnover of haplotypes through time. P. aeruginosa populations within each individual sputum sample harbored extensive diversity. Although we observed major changes in the haplotype composition within patients between samples taken at intervals of several months, the compositions varied much less during exacerbation periods, despite the use of intravenous antibiotics. Our data also highlight a correlation between periods of pulmonary exacerbation and the overproduction of pyocyanin, a quorum sensing-controlled virulence factor.
  
  
  CONCLUSIONS
  These results significantly advance our understanding of the within-host population biology of P. aeruginosa during infection of patients with cystic fibrosis, and provide in vivo evidence for a link between pyocyanin production and patient morbidity.
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool L69 3GA, UK.
authors.forename: Eilidh
authors.initials: E
authors.lastname: Mowat
authors.forename: Steve
authors.initials: S
authors.lastname: Paterson
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Fothergill
authors.forename: Elli A
authors.initials: EA
authors.lastname: Wright
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Ledson
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Walshaw
authors.forename: Michael A
authors.initials: MA
authors.lastname: Brockhurst
authors.forename: Craig
authors.initials: C
authors.lastname: Winstanley
mesh_terms: D000328:Adult; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications / Q000382:microbiology*; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008171:Lung Diseases / Q000382:microbiology*; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D011710:Pyocyanine / Q000096:biosynthesis; D013183:Sputum / Q000382:microbiology
chemical_list: D011710:Pyocyanine