Abstract

BackgroundStaphylococcus aureus has a high prevalence in chronic rhinosinusitis (CRS) patients and is suggested to play a more etiopathogenic role in CRS patients with nasal polyps (CRSwNP), a severe form of the CRS spectrum with poorer surgical outcomes. We performed a microbial genome-wide association study (mGWAS) to investigate whether S. aureus isolates from CRS patients have particular genetic markers associated with CRS with nasal polyps (CRSwNP) or CRS without nasal polyps (CRSsNP).MethodsWhole genome sequencing was performed on S. aureus isolates collected from 28 CRSsNP and 30 CRSwNP patients. A mGWAS approach was employed using large-scale comparative genomics to identify genetic variation within our dataset.ResultsConsiderable genetic variation was observed, with > 90,000 single nucleotide polymorphisms (SNPs) sites identified. There was little correlation with CRS subtype based on SNPs and Insertion/Delection (Indels). One indel was found to significantly correlate with CRSwNP and occurred in the promoter region of a bacitracin transport system ATP-binding protein. Additionally, two variants of the highly variable superantigen-like (SSL) proteins were found to significantly correlate with each CRS phenotype. No significant association with other virulence or antibiotic resistance genes were observed, consistent with previous studies.ConclusionTo our knowledge this study is the first to use mGWAS to investigate the contribution of microbial genetic variation to CRS presentations. Utilising the most comprehensive genome-wide analysis methods available, our results suggest that CRS phenotype may be influenced by genetic factors other than specific virulence mechanisms within the S. aureus genome.

Highlights

  • Staphylococcus aureus has a high prevalence in chronic rhinosinusitis (CRS) patients and is suggested to play a more etiopathogenic role in CRS patients with nasal polyps (CRSwNP), a severe form of the CRS spectrum with poorer surgical outcomes

  • Multilocus sequence typing Among the 58 S. aureus isolates collected for this study, 23 sequence types (STs) were identified

  • The V8 protease was identified in almost all isolates (92% CRS without nasal polyps (CRSsNP), 96% CRS with nasal polyps (CRSwNP)) while the SPLs were seen in 42% (SplA CRSsNP) and 76% (SplF CSRwNP)

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Summary

Introduction

Staphylococcus aureus has a high prevalence in chronic rhinosinusitis (CRS) patients and is suggested to play a more etiopathogenic role in CRS patients with nasal polyps (CRSwNP), a severe form of the CRS spectrum with poorer surgical outcomes. We performed a microbial genome-wide association study (mGWAS) to investigate whether S. aureus isolates from CRS patients have particular genetic markers associated with CRS with nasal polyps (CRSwNP) or CRS without nasal polyps (CRSsNP). CRS is phenotypically subclassified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). The immune barrier hypothesis is the most detailed and inclusive mechanism described in the literature This theory proposes that a defective host mucosal barrier and the innate immune response predispose CRS patients to mucosal inflammation when colonized by commensal bacteria that would otherwise not cause disease [7]

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