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. / Thesis / Master of Science (MSc) / Cystic fibrosis is a life-threatening disease characterized by cycles of stability and
respiratory illness. Bacterial species within the lungs of these patients are the main
contributor to disease progression. I investigated a specific transmissible epidemic
strain, Pseudomonas aeruginosa Prairie Epidemic Strain, using a unique collection
of samples provided by collaborators at the adult cystic fibrosis clinic in Calgary.
Using these samples, I first explored the differences between patients over a period
of 34 years. I hypothesized that similar changes in genome sequences will be
observed in multiple patients with a possible commonality in disease progression.
Second, I explored the role this bacterial pathogen may play in cycles of respiratory
illness. I hypothesize that a specific bacterial subpopulation could initiate these
cycles and be identified by changes at the genome level. This research provides
further knowledge of an epidemic strain of cystic fibrosis.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/24279 |
| Date | January 2018 |
| Creators | Szymkiewicz, Rachelle |
| Contributors | Surette, Michael, Biochemistry and Biomedical Sciences |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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