Title |
Genotypic Diversity within a Single Pseudomonas aeruginosa Strain Commonly Shared by Australian Patients with Cystic Fibrosis
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Published in |
PLOS ONE, December 2015
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DOI | 10.1371/journal.pone.0144022 |
Pubmed ID | |
Authors |
Anna Sze Tai, Scott Cameron Bell, Timothy James Kidd, Ella Trembizki, Cameron Buckley, Kay Annette Ramsay, Michael David, Claire Elizabeth Wainwright, Keith Grimwood, David Mark Whiley |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 3 | 30% |
Australia | 2 | 20% |
Brazil | 1 | 10% |
Unknown | 4 | 40% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 5 | 50% |
Scientists | 3 | 30% |
Practitioners (doctors, other healthcare professionals) | 2 | 20% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Germany | 1 | 2% |
Canada | 1 | 2% |
Unknown | 47 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 10 | 20% |
Researcher | 9 | 18% |
Student > Ph. D. Student | 7 | 14% |
Student > Bachelor | 4 | 8% |
Student > Doctoral Student | 4 | 8% |
Other | 8 | 16% |
Unknown | 7 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 9 | 18% |
Agricultural and Biological Sciences | 9 | 18% |
Immunology and Microbiology | 8 | 16% |
Biochemistry, Genetics and Molecular Biology | 5 | 10% |
Nursing and Health Professions | 2 | 4% |
Other | 7 | 14% |
Unknown | 9 | 18% |