Staphylococcus aureusbiofilm secreted factors cause mucosal damage, mast cell infiltration and goblet cell hyperplasia in a rat rhinosinusitis model

Abstract

AbstractChronic Rhinosinusitis (CRS) is an inflammatory condition of the paranasal sinus mucosa. Despite being a common health issue, the exact cause of CRS is yet to be understood. However, research suggests thatStaphylococcus aureus, particularly in the biofilm form, drives the disease. This study aimed to investigate the impact of long-term exposure to secreted factors ofStaphylococcus aureusbiofilm (SABSF), harvested from clinical isolates of non-CRS carriers and CRS patients, on the nasal mucosa in a rat model.Wistar rats were randomised (n=5/group) to receive daily intranasal instillations of 40 μL (200 μg/μL) SABSF for 28 days or vehicle control withS. aureusisolated from the sinuses of a non-CRS carrier, a type 2 endotype CRS with nasal polyps (CRSwNP) patient, and a non-type 2 endotype CRS without nasal polyps (CRSsNP) patient. The sinonasal samples of the rats were then analysed through histopathology and transcriptome profiling.The results showed that all three intervention groups displayed significant lymphocytic infiltration (p≤0.05). However, only the SABSF collected from the CRSwNP patient caused significant mucosal damage, mast cell infiltration, and goblet cell hyperplasia compared to the control. The transcriptomics results indicated that SABSF significantly enriched multiple inflammatory pathways and showed distinct transcriptional expression differences between the control group and the SABSF collected from CRS patients (p≤0.05). Additionally, the SABSF challenges induced the expression of IgA and IgG but not IgE.In conclusion, thisin vivostudy indicates that long-term exposure to SABSF leads to an inflammatory response in the nasal mucosa with increased severity forS. aureusisolated from a CRSwNP patient. The findings of this study shed light on the role ofS. aureusin the development of CRS and could inform future research and treatment efforts.