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Williams, David, Fothergill, Joanne L, Evans, Benjamin 
ORCID: https://orcid.org/0000-0001-6849-9758, Caples, Jessica, Haldenby, Sam, Walshaw, Martin J, Brockhurst, Michael A, Winstanley, Craig and Paterson, Steve
(2018)
Transmission and lineage displacement drive rapid population genomic flux in cystic fibrosis airway infections of a Pseudomonas aeruginosa epidemic strain.
Microbial Genomics, 4 (3).
ISSN 2057-5858
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Abstract
Pseudomonas aeruginosa chronic infections of cystic fibrosis (CF) airways are a paradigm for within-host evolution with abundant evidence for rapid evolutionary adaptation and diversification. Recently emerged transmissible strains have spread globally, with the Liverpool Epidemic Strain (LES) the most common strain infecting the UK CF population. Previously we have shown that highly divergent lineages of LES can be found within a single infection, consistent with super-infection among a cross-sectional cohort of patients. However, despite its clinical importance, little is known about the impact of transmission on the genetic structure of these infections over time. To characterize this, we longitudinally sampled a meta-population of 15 genetic lineages within the LES over 13 months among seven chronically infected CF patients by genome sequencing. Comparative genome analyses of P. aeruginosa populations revealed that the presence of coexisting lineages contributed more to genetic diversity within an infection than diversification in situ. We observed rapid and substantial shifts in the relative abundance of lineages and replacement of dominant lineages, likely to represent super-infection by repeated transmissions. Lineage dynamics within patients led to rapid changes in the frequencies of mutations across suites of linked loci carried by each lineage. Many loci were associated with important infection phenotypes such as antibiotic resistance, mucoidy and quorum sensing, and were repeatedly mutated in different lineages. These findings suggest that transmission leads to rapid shifts in the genetic structure of CF infections, including in clinically important phenotypes such as antimicrobial resistance, and is likely to impede accurate diagnosis and treatment.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | competition,cystic fibrosis,pseudomonas,pathogen evolution,chronic infection |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Pathogen Biology Group |
| Depositing User: | Pure Connector |
| Date Deposited: | 04 Apr 2018 13:30 |
| Last Modified: | 23 Oct 2024 00:57 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/66654 |
| DOI: | 10.1099/mgen.0.000167 |
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