title: Phenotypic diversity within a Pseudomonas aeruginosa population infecting an adult with cystic fibrosis.
abstract: Chronic airway infections caused by Pseudomonas aeruginosa contribute to the progression of pulmonary disease in individuals with cystic fibrosis (CF). In the setting of CF, within-patient adaptation of a P. aeruginosa strain generates phenotypic diversity that can complicate microbiological analysis of patient samples. We investigated within- and between- sample diversity of 34 phenotypes among 235 P. aeruginosa isolates cultured from sputum samples collected from a single CF patient over the span of one year, and assessed colony morphology as a screening tool for predicting phenotypes, including antimicrobial susceptibilities. We identified 15 distinct colony morphotypes that varied significantly in abundance both within and between sputum samples. Substantial within sample phenotypic heterogeneity was also noted in other phenotypes, with morphotypes being unreliable predictors of antimicrobial susceptibility and other phenotypes. Emergence of isolates with reduced susceptibility to β-lactams was observed during periods of clinical therapy with aztreonam. Our findings confirm that the P. aeruginosa population in chronic CF lung infections is highly dynamic, and that intra-sample phenotypic diversity is underestimated if only one or few colonies are analyzed per sample.
authors.affiliation: 1] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada [2] Latner Thoracic Surgery Research Laboratories, University Health Network, Toronto, Canada.
authors.forename: Shawn T
authors.initials: ST
authors.lastname: Clark
authors.affiliation: Department of Cell &Systems Biology, University of Toronto, Toronto, Canada.
authors.forename: Julio
authors.initials: J
authors.lastname: Diaz Caballero
authors.affiliation: Latner Thoracic Surgery Research Laboratories, University Health Network, Toronto, Canada.
authors.forename: Mary
authors.initials: M
authors.lastname: Cheang
authors.affiliation: Department of Cell &Systems Biology, University of Toronto, Toronto, Canada.
authors.forename: Bryan
authors.initials: B
authors.lastname: Coburn
authors.affiliation: 1] Department of Cell &Systems Biology, University of Toronto, Toronto, Canada [2] Centre for the Analysis of Genome Evolution &Function, University of Toronto, Toronto, Canada.
authors.forename: Pauline W
authors.initials: PW
authors.lastname: Wang
authors.affiliation: Centre for the Analysis of Genome Evolution &Function, University of Toronto, Toronto, Canada.
authors.forename: Sylva L
authors.initials: SL
authors.lastname: Donaldson
authors.affiliation: Latner Thoracic Surgery Research Laboratories, University Health Network, Toronto, Canada.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Latner Thoracic Surgery Research Laboratories, University Health Network, Toronto, Canada.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Latner Thoracic Surgery Research Laboratories, University Health Network, Toronto, Canada.
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.affiliation: 1] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada [2] Department of Pediatric Laboratory Medicine, Division of Microbiology, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Yvonne C W
authors.initials: YC
authors.lastname: Yau
authors.affiliation: 1] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada [2] Department of Pediatrics, Division of Infectious Diseases, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Waters
authors.affiliation: Department of Medicine, Division of Respirology, St. Michael's Hospital, Toronto, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Elizabeth Tullis
authors.affiliation: 1] Department of Cell &Systems Biology, University of Toronto, Toronto, Canada [2] Centre for the Analysis of Genome Evolution &Function, University of Toronto, Toronto, Canada.
authors.forename: David S
authors.initials: DS
authors.lastname: Guttman
authors.affiliation: 1] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada [2] Latner Thoracic Surgery Research Laboratories, University Health Network, Toronto, Canada [3] Laboratory Medicine Program, University Health Network, Toronto, Canada.
authors.forename: David M
authors.initials: DM
authors.lastname: Hwang
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D003550:Cystic Fibrosis / Q000382:microbiology*; D005260:Female; D006801:Humans; D010641:Phenotype; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000302:isolation & purification; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000382:microbiology*; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents