The Adaption and Inflammation-Inducing Capacity of Staphylococcus Aureus in Chronic Rhinosinusitis
Files
(Thesis)
Date
2023
Authors
Houtak, Ghais
Editors
Advisors
Vreugde, Sarah
Psaltis, Alkis
Wormald, Peter John
Psaltis, Alkis
Wormald, Peter John
Journal Title
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Thesis
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Abstract
Chronic rhinosinusitis (CRS) is a common chronic sinonasal mucosal inflammation associated with Staphylococcus aureus colonisation and biofilm presence. This thesis aimed to determine rates of S. aureus persistence and pathoadaptation in CRS patients by investigating the genomic relatedness and antibiotic tolerance in longitudinally collected S. aureus clinical isolates. Moreover, an in-depth analysis was performed on 8 sequential longitudinal isolates from a severe CRS patient's sinonasal cavity spanning 672 days. Lastly, this thesis investigated the impact of long-term exposure to secreted factors of Staphylococcus aureus biofilm (SABSF), harvested from clinical isolates of non-CRS carriers and CRS patients, on the nasal mucosa in a rat model. Persister isolates often showed changes in mobile genetic elements, indicating the involvement of the 'mobilome' in promoting persistence. The genomic adaptation of persister isolates was episode-specific, however, an increase in biofilm tolerance to antibiotics was observed on a population level. The in-depth analysis of the 8 sequential isolates analysis revealed the genetic evolution of a high biofilm-forming S. aureus strain towards a hyper biofilm-forming mucoid phenotype. The hyper biofilm-forming mucoid phenotype was able to dominate the niche for a prolonged time, suggesting that the high-level production of biofilm could confer an advantage in sinuses. Lastly, long-term exposure to SABSF led to an inflammatory response resembling the inflammation seen in CRS patients, with S. aureus from CRSwNP patients eliciting a more intense response.
School/Discipline
Adelaide Medical School
Dissertation Note
Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2023
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