S. aureus biofilm properties correlate with immune B cell subset frequencies and severity of chronic rhinosinusitis

Gohar Shaghayegh; Clare Cooksley; George Bouras; Beula Subashini Panchatcharam; Sholeh Feizi; Shari Javadian; Mahnaz Ramezanpour; Kevin Aaron Fenix; Peter-John Wormald; Alkis James Psaltis; Sarah Vreugde

doi:10.1016/j.clim.2024.110221

S. aureus biofilm properties correlate with immune B cell subset frequencies and severity of chronic rhinosinusitis

Clin Immunol. 2024 Apr 16:263:110221. doi: 10.1016/j.clim.2024.110221. Online ahead of print.

Affiliations

¹ Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia; The Department of Surgery-Otolaryngology, Head and Neck Surgery, University of Adelaide and the Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, South Australia, Australia.
² Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia; The Department of Surgery-Otolaryngology, Head and Neck Surgery, University of Adelaide and the Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, South Australia, Australia. Electronic address: sarah.vreugde@adelaide.edu.au.

PMID: 38636891
DOI: 10.1016/j.clim.2024.110221

Abstract

Staphylococcus aureus mucosal biofilms are associated with recalcitrant chronic rhinosinusitis (CRS). However, S. aureus colonisation of sinus mucosa is frequent in the absence of mucosal inflammation. This questions the relevance of S. aureus biofilms in CRS etiopathogenesis. This study aimed to investigate whether strain-level variation in in vitro-grown S. aureus biofilm properties relates to CRS disease severity, in vitro toxicity, and immune B cell responses in sinonasal tissue from CRS patients and non-CRS controls. S. aureus clinical isolates, tissue samples, and matched clinical datasets were collected from CRS patients with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and controls. B cell responses in tissue samples were characterised by FACS. S. aureus biofilms were established in vitro, followed by measuring their properties of metabolic activity, biomass, colony-forming units, and exoprotein production. S. aureus virulence was evaluated using whole-genome sequencing, mass spectrometry and application of S. aureus biofilm exoproteins to air-liquid interface cultures of primary human nasal epithelial cells (HNEC-ALI). In vitro S. aureus biofilm properties were correlated with increased CRS severity scores, infiltration of antibody-secreting cells and loss of regulatory B cells in tissue samples. Biofilm exoproteins from S. aureus with high biofilm metabolic activity had enriched virulence genes and proteins, and negatively affected the barrier function of HNEC-ALI cultures. These findings support the notion of strain-level variation in S. aureus biofilms to be critical in the pathophysiology of CRS.

Keywords: Antibody-secreting cells; Chronic rhinosinusitis; Disease severity; Regulatory B cells; S. aureus biofilm; Sinonasal mucosa; Virulence proteins.