Maggie A Middleton1, Mehdi Layeghifard2, Michelle Klingel3, Sanja Stanojevic3, Yvonne C W Yau4, James E A Zlosnik5, Adele Coriati6, Felix A Ratjen3, Elizabeth D Tullis7, Anne Stephenson7, Pearce Wilcox8, Andreas Freitag9, Mark Chilvers10, Martha McKinney11, Annick Lavoie6, Pauline W Wang1, David S Guttman1,2, Valerie J Waters12. 1. 1 Centre for the Analysis of Genome Evolution and Function, and. 2. 2 Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada. 3. 3 Division of Respiratory Medicine, Department of Pediatrics and Translational Medicine. 4. 4 Division of Microbiology, Department of Pediatric Laboratory Medicine, and. 5. 5 Division of Infectious Diseases, Department of Pediatrics, Centre for Understanding and Preventing Infection in Children, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada. 6. 6 Division of Respiratory Medicine and Critical Care, Department of Medicine, Hotel Dieu Hospital, Montreal, Quebec, Canada. 7. 7 Division of Respirology and Keenan Research Centre of Li Ka Shing Knowledge Institute, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. 8. 8 Division of Respiratory Medicine, Department of Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada. 9. 9 Division of Respiratory Medicine, Department of Medicine, Hamilton Health Sciences Center, McMaster University, Hamilton, Ontario, Canada. 10. 10 Division of Respiratory Medicine, Department of Pediatrics, British Columbia Children's Hospital, Vancouver, British Columbia, Canada; and. 11. 11 Division of Respiratory Medicine, Department of Pediatrics, Ste. Justine Hospital, Montreal, Quebec, Canada. 12. 12 Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Abstract
RATIONALE: The extent of the genetic relatedness among Pseudomonas aeruginosa isolates and its impact on clinical outcomes in the cystic fibrosis (CF) population is poorly understood. OBJECTIVES: The objectives of this study were to determine the prevalence of clonal P. aeruginosa infection in Canada and to associate P. aeruginosa genotypes with clinical outcomes. METHODS: This was an observational study of adult and pediatric patients with CF across Canada. Isolates were typed using multilocus sequence typing. A clone was defined as sharing at least six of seven alleles. Genotyping results were associated with clinical outcomes, including forced expiratory volume in 1 second, body mass index, rate of pulmonary exacerbation, and death/transplant. RESULTS: A total of 1,537 P. aeruginosa isolates were genotyped to 403 unique sequence types (STs) in 402 individuals with CF. Although 39% of STs were shared, most were shared only among a small number of subjects, and the majority (79%) of the genetic diversity in P. aeruginosa isolates was observed between patients. There were no significant differences in clinical outcomes according to genotype. However, patients with a dynamic, changing ST infection pattern had both a steeper decline in forced expiratory volume in 1 second (-2.9% predicted change/yr, 95% confidence interval [CI] = -3.8 to -1.9 compared with 0.4, 95% CI = -0.3 to 1.0; P < 0.001) and body mass index (-1.0 percentile change/yr, 95% CI = -1.6 to -0.3 compared with -0.1, 95% CI = -0.7 to 0.5; P = 0.047) than those with a stable infection with the same ST. CONCLUSIONS: There was no widespread sharing of dominant clones in our CF population, and the majority of the genetic diversity in P. aeruginosa was observed between patients. Changing genotypes over time within an individual was associated with worse clinical outcomes.
RATIONALE: The extent of the genetic relatedness among Pseudomonas aeruginosa isolates and its impact on clinical outcomes in the cystic fibrosis (CF) population is poorly understood. OBJECTIVES: The objectives of this study were to determine the prevalence of clonal P. aeruginosa infection in Canada and to associate P. aeruginosa genotypes with clinical outcomes. METHODS: This was an observational study of adult and pediatric patients with CF across Canada. Isolates were typed using multilocus sequence typing. A clone was defined as sharing at least six of seven alleles. Genotyping results were associated with clinical outcomes, including forced expiratory volume in 1 second, body mass index, rate of pulmonary exacerbation, and death/transplant. RESULTS: A total of 1,537 P. aeruginosa isolates were genotyped to 403 unique sequence types (STs) in 402 individuals with CF. Although 39% of STs were shared, most were shared only among a small number of subjects, and the majority (79%) of the genetic diversity in P. aeruginosa isolates was observed between patients. There were no significant differences in clinical outcomes according to genotype. However, patients with a dynamic, changing ST infection pattern had both a steeper decline in forced expiratory volume in 1 second (-2.9% predicted change/yr, 95% confidence interval [CI] = -3.8 to -1.9 compared with 0.4, 95% CI = -0.3 to 1.0; P < 0.001) and body mass index (-1.0 percentile change/yr, 95% CI = -1.6 to -0.3 compared with -0.1, 95% CI = -0.7 to 0.5; P = 0.047) than those with a stable infection with the same ST. CONCLUSIONS: There was no widespread sharing of dominant clones in our CF population, and the majority of the genetic diversity in P. aeruginosa was observed between patients. Changing genotypes over time within an individual was associated with worse clinical outcomes.
Entities:
Keywords:
Pseudomonas aeruginosa; clonal; cystic fibrosis; lung function
Authors: Julie Jeukens; Luca Freschi; Irena Kukavica-Ibrulj; Jean-Guillaume Emond-Rheault; Christian Allard; Jean Barbeau; André Cantin; Steve J Charette; Eric Déziel; François Malouin; Julie Milot; Dao Nguyen; Clara Popa; Brian Boyle; Roger C Levesque Journal: J Clin Microbiol Date: 2019-05-24 Impact factor: 5.948
Authors: Nicole Acosta; Barbara Waddell; Alya Heirali; Ranjani Somayaji; Michael G Surette; Matthew L Workentine; Harvey R Rabin; Michael D Parkins Journal: Front Cell Infect Microbiol Date: 2020-04-24 Impact factor: 5.293
Authors: Jacob Melamed; Alexander Kocev; Vladimir Torgov; Vladimir Veselovsky; Inka Brockhausen Journal: Glycoconj J Date: 2022-02-15 Impact factor: 3.009
Authors: Conrad Izydorczyk; Barbara J Waddell; Robert B Weyant; Michael G Surette; Ranjani Somayaji; Harvey R Rabin; John M Conly; Deirdre L Church; Michael D Parkins Journal: Sci Rep Date: 2022-09-21 Impact factor: 4.996
Authors: Marcus M Dillon; Tatiana Ruiz-Bedoya; Cedoljub Bundalovic-Torma; Kevin M Guttman; Haejin Kwak; Maggie A Middleton; Pauline W Wang; Sumer Horuz; Yesim Aysan; David S Guttman Journal: Microb Genom Date: 2021-07