Use this URL to cite or link to this record in EThOS:
Title: Comparative genomics of Pseudomonas aeruginosa populations
Author: Moore, Matthew Phillip
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2017
Availability of Full Text:
Access from EThOS:
Access from Institution:
Pseudomonas aeruginosa causes a wide range of infections, is often associated with antimicrobial resistance and is the primary cause of chronic lung infection in cystic fibrosis (CF) and the overall morbidity and mortality associated with the disease. As P. aeruginosa is an environmental bacterium that opportunistically infects CF patients most infecting lineages are distinct. The determination of common adaptive routes during infection is further complicated by within-lineage heterogeneity, multi-lineage infections and the emergence of transmissible strains. In order to better understand the genetic basis of varying pathogenicity, a diverse dataset of 1,407 P. aeruginosa genomes from the environment, non-CF bronchiectasis and from CF samples was analysed. Detailed analysis of mutations potentially associated with the CF lung environment was conducted by comparison of the genomes from CF and environmental isolates and by including a geographically and historically diverse panel of a transmissible lineage, the Liverpool Epidemic Strain (LES). Sequencing of isolates from non-CF bronchiectasis showed for the first time the commonality in adaptive routes in non-CF chronic lung diseases and the utility of genome sequencing to infer within and between host diversity and population structure. Many antibiotic resistance genes (ARGs) in all samples were observed to be adaptive and a sample of genomes from hospital isolates from Thailand was used to assess international multi-drug resistance lineages with mobile genetic element associated ARGs. This study has shown, by analysis of diverse datasets, how genome sequencing can reveal the genetic basis of phenotypic heterogeneity and subsequent varying patient outcomes with this diverse infection.
Supervisor: Winstanley, Craig ; Fothergill, Jo Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral