Identification of Novel Core and Accessory Virulence Patterns in Staphylococcus aureus-related Chronic Rhinosinusitis

Staphylococcus aureus commonly colonises the nasal cavities of both healthy individuals and patients with chronic rhinosinusitis (CRS) with (CRSwNP) and without (CRSsNP) nasal polyps. Recent evidence highlights the increased abundance of mobile genetic elements in S. aureus isolates from CRS patients, contributing virulence and antimicrobial resistance genes that facilitate survival and mediate treatment resistance. We hypothesised that S. aureus isolates from different disease states (non-diseased controls, CRSsNP and CRSwNP) would exhibit distinct patterns of virulence factors contributing to persistence and enhanced survival. We collected nasal swabs from 77 patients, culturing S. aureus in 8 controls, 8 CRSsNP patients and 5 CRSwNP patients. Isolates were sequenced using Illumina short-read paired-end sequencing and genomes were analysed for stress, antimicrobial resistance and virulence genes, along with the presence of plasmids and prophages. We identified four virulence factor gene patterns: a core set (hlgA, icaC, hlgB, hlgC, hld and aur) present in nearly all isolates, the core set plus accessory sets which include the enterotoxin gene cluster (seo, sem, seu, sei, sen) and a complete or partial invasive virulence factor set (splE, splA, splB, lukE and lukD) (p = 0.001). CRSwNP isolates showed degradation of the core set, with frequent loss of scn, icaC and hlgA (p < 0.05). Plasmids and prophages did not significantly contribute to virulence or antimicrobial resistance genes across the groups. These findings suggest that S. aureus has clusters of virulence factors which may act in concert to support survival and persistence of the bacteria resulting in a more pathogenic phenotype. This may manifest clinically with resistant disease and refractoriness to antibiotics.