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BMC Genomics. 2018 Aug 30;19(1):644. doi: 10.1186/s12864-018-5018-x.

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

Wee BA1,2, Tai AS3,4,5, Sherrard LJ6,7, Ben Zakour NL1, Hanks KR1, Kidd TJ1,8,9, Ramsay KA3,6,10, Lamont I11, Whiley DM12,13, Bell SC3,4,6,14, Beatson SA15,16,17.

Author information

1
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.
2
Present Address: Usher Institute of Population Health Sciences & Informatics, University of Edinburgh, Edinburgh, United Kingdom.
3
Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
4
Adult Cystic Fibrosis Centre, Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, QLD, Australia.
5
Department of Respiratory Medicine, Western Australia Adult Cystic Fibrosis Centre, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
6
Lung Bacteria Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
7
Present Address: School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom.
8
Centre for Experimental Medicine, Queen's University Belfast, Belfast, UK.
9
Child Health Research Centre, The University of Queensland, Brisbane, QLD, Australia.
10
Present Address: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
11
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
12
Faculty of Medicine, UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia.
13
Microbiology Department, Pathology Queensland Central Laboratory, Brisbane, QLD, Australia.
14
Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia.
15
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia. s.beatson@uq.edu.au.
16
Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia. s.beatson@uq.edu.au.
17
Australian Centre for Ecogenomics, The University of Queensland, Brisbane, QLD, Australia. s.beatson@uq.edu.au.

Abstract

BACKGROUND:

Chronic lung infections caused 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 non-hypermutator 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. Further genomic investigations are required on multiple intra-sample isolates of this sub-type to decipher potential mechanisms which facilitates its epidemiological success.

KEYWORDS:

AUST-02; Chronic lung infections; Cystic fibrosis; Evolution; Pseudomonas aeruginosa; Whole genome sequencing

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