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Whole genome sequencing reveals the emergence of a Pseudomonas aeruginosa shared strain sub-lineage among patients treated within a single cystic fibrosis centre

View ORCID ProfileBryan A. Wee, Anna S. Tai, Laura J. Sherrard, Nouri L. Ben Zakour, Kirt R. Hanks, Timothy J. Kidd, Kay A. Ramsay, Iain Lamont, David M. Whiley, Scott C. Bell, View ORCID ProfileScott A. Beatson
doi: https://doi.org/10.1101/261586
Bryan A. Wee
1School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
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Anna S. Tai
2Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
4Western Australia Adult Cystic Fibrosis Centre, Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Western Australia, Australia
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Laura J. Sherrard
5Lung Bacteria Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
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Nouri L. Ben Zakour
1School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
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Kirt R. Hanks
1School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
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Timothy J. Kidd
1School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
6Centre for Experimental Medicine, Queen’s University Belfast, Belfast, UK
7Child Health Research Centre, The University of Queensland, Brisbane, QLD, Australia
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Kay A. Ramsay
2Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
5Lung Bacteria Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
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Iain Lamont
8Department of Biochemistry, University of Otago, Dunedin, New Zealand
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David M. Whiley
9Faculty of Medicine, UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia
10Microbiology Department, Pathology Queensland Central Laboratory, Brisbane, QLD, Australia
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Scott C. Bell
2Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
3Adult Cystic Fibrosis Centre, Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, QLD, Australia
5Lung Bacteria Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
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Scott A. Beatson
1School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
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  • For correspondence: s.beatson@uq.edu.au
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Abstract

Background Chronic lung infections by Pseudomonas aeruginosa are a significant cause of morbidity and mortality in people with cystic fibrosis (CF). Shared P. aeruginosa strains, that can be transmitted between patients, are of concern and in Australia the AUST-02 shared strain is predominant in individuals attending CF centres in Queensland and Western Australia. M3L7 is a multidrug resistant sub-type of AUST-02 that was recently identified in a Queensland CF centre and was shown to be associated with poorer clinical outcomes. The main aim of this study was to resolve the relationship of the emergent M3L7 sub-type within the AUST-02 group of strains using whole genome sequencing.

Results A whole-genome core phylogeny of 63 isolates indicated that M3L7 is a monophyletic sub-lineage within the context of the broader AUST-02 group. Relatively short branch lengths connected all of the M3L7 isolates. A phylogeny based on nucleotide polymorphisms present across the genome showed that the chronological estimation of the most recent common ancestor was around 2001 (± 3 years). SNP differences between sequential M3L7 isolates collected 3-4 years apart from five patients suggested both continuous infection of the same strain and cross-infection of some M3L7 variants between patients. The majority of polymorphisms that were characteristic of M3L7 (i.e. acquired after divergence from all other AUST-02 isolates sequenced) were found to produce non-synonymous mutations in virulence and antibiotic resistance genes.

Conclusions M3L7 has recently diverged from a common ancestor indicating descent from a single carrier at a CF treatment centre in Australia. Both adaptation to the lung and transmission of M3L7 between adults attending this centre may have contributed to its rapid dissemination. The study emphasises the importance of clinical management in controlling the emergence of shared strains in CF.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted March 08, 2018.
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Whole genome sequencing reveals the emergence of a Pseudomonas aeruginosa shared strain sub-lineage among patients treated within a single cystic fibrosis centre
Bryan A. Wee, Anna S. Tai, Laura J. Sherrard, Nouri L. Ben Zakour, Kirt R. Hanks, Timothy J. Kidd, Kay A. Ramsay, Iain Lamont, David M. Whiley, Scott C. Bell, Scott A. Beatson
bioRxiv 261586; doi: https://doi.org/10.1101/261586
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Whole genome sequencing reveals the emergence of a Pseudomonas aeruginosa shared strain sub-lineage among patients treated within a single cystic fibrosis centre
Bryan A. Wee, Anna S. Tai, Laura J. Sherrard, Nouri L. Ben Zakour, Kirt R. Hanks, Timothy J. Kidd, Kay A. Ramsay, Iain Lamont, David M. Whiley, Scott C. Bell, Scott A. Beatson
bioRxiv 261586; doi: https://doi.org/10.1101/261586

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