Genotypic Diversity within a Single Pseudomonas aeruginosa Strain Commonly Shared by Australian Patients with Cystic Fibrosis

Tai, Anna Sze, Bell, Scott Cameron, Kidd, Timothy James, Trembizki, Ella, Buckley, Cameron, Ramsay, Kay Annette, David, Michael, Wainwright, Claire Elizabeth, Grimwood, Keith and Whiley, David Mark (2015) Genotypic Diversity within a Single Pseudomonas aeruginosa Strain Commonly Shared by Australian Patients with Cystic Fibrosis. Plos One, 10 12: . doi:10.1371/journal.pone.0144022

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Author Tai, Anna Sze
Bell, Scott Cameron
Kidd, Timothy James
Trembizki, Ella
Buckley, Cameron
Ramsay, Kay Annette
David, Michael
Wainwright, Claire Elizabeth
Grimwood, Keith
Whiley, David Mark
Title Genotypic Diversity within a Single Pseudomonas aeruginosa Strain Commonly Shared by Australian Patients with Cystic Fibrosis
Journal name Plos One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2015-12-03
Year available 2015
Sub-type Article (original research)
DOI 10.1371/journal.pone.0144022
Open Access Status DOI
Volume 10
Issue 12
Total pages 17
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted abstract
In cystic fibrosis (CF), Pseudomonas aeruginosa undergoes intra-strain genotypic and phenotypic diversification while establishing and maintaining chronic lung infections. As the clinical significance of these changes is uncertain, we investigated intra-strain diversity in commonly shared strains from CF patients to determine if specific gene mutations were associated with increased antibiotic resistance and worse clinical outcomes. Two-hundred-and-one P. aeruginosa isolates (163 represented a dominant Australian shared strain, AUST-02) from two Queensland CF centres over two distinct time-periods (2001–2002 and 2007–2009) underwent mexZ and lasR sequencing. Broth microdilution antibiotic susceptibility testing in a subset of isolates was also performed. We identified a novel AUST-02 subtype (M3L7) in adults attending a single Queensland CF centre. This M3L7 subtype was multi-drug resistant and had significantly higher antibiotic minimum inhibitory concentrations than other AUST-02 subtypes. Prospective molecular surveillance using polymerase chain reaction assays determined the prevalence of the ‘M3L7’ subtype at this centre during 2007–2009 (170 patients) and 2011 (173 patients). Three-year clinical outcomes of patients harbouring different strains and subtypes were compared. MexZ and LasR sequences from AUST-02 isolates were more likely in 2007–2009 than 2001–2002 to exhibit mutations (mexZ: odds ratio (OR) = 3.8; 95% confidence interval (CI): 1.1–13.5 and LasR: OR = 2.5; 95%CI: 1.3–5.0). Surveillance at the adult centre in 2007–2009 identified M3L7 in 28/509 (5.5%) P. aeruginosa isolates from 13/170 (7.6%) patients. A repeat survey in 2011 identified M3L7 in 21/519 (4.0%) P. aeruginosa isolates from 11/173 (6.4%) patients. The M3L7 subtype was associated with greater intravenous antibiotic and hospitalisation requirements, and a higher 3-year risk of death/lung transplantation, than other AUST-02 subtypes (adjusted hazard ratio [HR] = 9.4; 95%CI: 2.2–39.2) and non-AUST-02 strains (adjusted HR = 4.8; 95%CI: 1.4–16.2). This suggests ongoing microevolution of the shared CF strain, AUST-02, was associated with an emerging multi-drug resistant subtype and possibly poorer clinical outcomes.
Keyword Transmissible Strains
Lung Infections
Lasr Mutants
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

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