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http://hdl.handle.net/11375/24279
Title: | Pseudomonas aeruginosa Prairie Epidemic Strain Population Dynamics and Evolution of Disease in Cystic Fibrosis Airways of Adult Patients |
Authors: | Szymkiewicz, Rachelle |
Advisor: | Surette, Michael |
Department: | Biochemistry and Biomedical Sciences |
Keywords: | Cystic Fibrosis;Comparative genomics;Population dynamics |
Publication Date: | 2018 |
Abstract: | The lower airways of patients with chronic airway diseases including cystic fibrosis (CF) are colonized by diverse communities of microorganisms. Over-time the airways of some 60% of CF patients become permanently colonized and dominated by Pseudomonas aeruginosa. Chronic infection of P. aeruginosa has been associated with a decline in pulmonary function, worse prognosis, and eventual patient mortality. Although P. aeruginosa evolves within the CF airways resulting in complex populations, the mechanism by which these complex populations contribute to disease progression is not well understood. Here we show diversity among isolates by observed changes in genome sequences of a strain of P. aeruginosa, known as Prairie Epidemic Strain (PES). Using whole genome sequencing and comparative genomics we identified a large core genome across 195 PES isolates from 57 CF patients of the Calgary Adult Cystic Fibrosis Clinic (CACFC) where 88% of the pangenome was categorized as core genes. Single nucleotide polymorphism (SNPs) mutations were shown to be the largest contributor of diversity at the nucleotide level compared to other polymorphism types consisting of 87% of the total polymorphisms present across the 195 PES isolates. CRISPR arrays and mobile elements such as prophage and plasmids demonstrate this strain of P. aeruginosa was stable over 30 years. In a second aim, I show variation in the populations of P. aeruginosa across an exacerbation event further highlighting the complexity of the lung bacterial community. Distinct populations of P. aeruginosa at the onset and resolution of an exacerbation within a single CF patient were identified by SNPs. These results a model where adaptive radiation as well as natural mutations contribute to the heterogeneity and diversification within populations of P. aeruginosa in CF patients. Understanding the evolution and population structure of PES through the identification of important genes and mutations through the clinical course of an exacerbation can aid in identifying new targets for patient treatment of P. aeruginosa in CF. |
URI: | http://hdl.handle.net/11375/24279 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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SZYMKIEWICZ_RACHELLE_S_2018SEPT_MSc.pdf | 6.2 MB | Adobe PDF | View/Open |
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