Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/127758
Type: Thesis
Title: Staphylococcus aureus Exoproteins on Nasal Epithelial Barrier in Chronic Rhinosinusitis
Author: Panchatcharam, Beula Subashini
Issue Date: 2020
School/Discipline: Adelaide Medical School
Abstract: Chronic Rhinosinusitis (CRS) is characterised by a plethora of symptoms that patients suffer as a result of chronic inflammation of the sinus mucosa. These are associated with chronic relapsing infections caused by mucosal biofilms that are predominantly due to Staphylococcus aureus. CRS is a prevalent disease affecting around 10% of the general population in Western societies with significant impact on the socio-economical life. However, the pathophysiology of CRS and exact role of biofilms and S. aureus infections are poorly understood. Therefore, understanding the mechanism by which these micro-organisms and biofilms affect the mucosa and relate to chronic inflammation and relapsing infections is subject of intense ongoing research worldwide. The first part of this thesis studied the pathogenicity of S. aureus clinical isolates isolated from patients who were suffering from CRS and that were grown in planktonic form and biofilm form. We collected the exoproteins secreted from those isolates and studied their effect on in-vitro models of the nasal epithelial barrier. As a result of this study we found S. aureus biofilm exoproteins disrupt the mucosal barrier structure in a time- and dose- dependent manner and are toxic to the barrier. This damage to the mucosal barrier is thought to play an important role in the etiopathogenesis of CRS. In the second part of the thesis we explored the ability of S. aureus biofilms to induce a host immune response and we studied the relationship between S. aureus biofilm properties and host immune responses. S. aureus clinical isolates harvested from CRSwNP patients exhibited higher S. aureus biofilm exoprotein production and higher metabolic activity than S. aureus biofilms from CRSsNP patients. There was a significant strong positive correlation between the number of lymphocytes or eosinophils and the concentration of biofilm exoproteins secreted by corresponding clinical isolates and their metabolic activity. In contrast, exoprotein concentrations from planktonic cells did not correlate with inflammatory cell infiltration. The gradual increase in inflammation and Th2 polarisation in relation to S. aureus biofilm properties seen in that study imply that biofilm exoproteins might trigger inflammation in those patients. The third part of this thesis involved studying the resistance pattern of S. aureus in planktonic and biofilm form, and to know if they were any different in their sensitivity to commonly used antibiotics used in routine clinical practice. By doing so it was our aim to show that persistence and severity of symptoms in recalcitrant (rCRS) disease is due to biofilms that resist treatment to conventional antibiotics, many times higher than their planktonic counterparts. We were able to show that S. aureus biofilm have unique properties of excessive exoprotein production which was directly proportionate to their biomass and metabolic activity. The minimum dosage for biofilm eradication (MBEC) was much higher than routinely used minimum inhibitory concentration (MIC) of planktonic forms of the organisms. MBEC values furthermore correlated with inflammatory cell counts, giving us valuable insights into the mechanisms by which the organism evade treatment and induce human suffering. This study helps us to design future experiments in-vivo and study human response conditions thereby paving ways as a model for future therapies that could target the microorganism’s exoprotein production.
Advisor: Wormald, Peter John
Dissertation Note: Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2020
Keywords: S. aureus
epithelial barrier
exoproteins
chronic rhinosinusitis
Provenance: This thesis is currently under Embargo and not available.
Appears in Collections:Research Theses

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