Prevalence and production of superantigen exotoxins by cystic fibrosis Staphylococcus aureus isolates

Abstract

Staphylococcus aureus (SA) is the most common cystic fibrosis (CF) lung pathogen that is uniquely capable of producing superantigen (SAg) exotoxins, which are recognized as the most potent activators of the immune system and inducers of inflammation. Herein, we analyzed the distribution of SA-SAgs among pediatric and adult CF clinical isolates. We then investigated the production of biologically active SA-SAgs by some of these clinical isolates and tested the stability of SA-SAg in CF sputum. We demonstrate that 60-80 % of pediatric and adult CF SA isolates carried at least one SA-SAg gene, with the former harboring potent SA-SAgs (Staphylococcal enterotoxin A and B) more frequently (30-60 %) which may explain why the presence of SA associates with poorer respiratory outcomes in pediatric CF. Biofilms of clinical SA isolates readily produced biologically active SA-SAgs in artificial sputum medium and purified SA-SAgs retained their bioactivity in human CF sputum in vitro. Further, the immunostimulatory potential of the CF SA isolates depended on their SAg profile. Overall, our study confirms that SA-SAgs are widely prevalent in CF SA isolates. However, the immunostimulatory potential of these isolates varied depending on their SAg profile which may explain the heterogeneity in clinical presentation of CF lung disease.

Keywords: Cystic fibrosis; Cytokines; Staphylococcus aureus; Superantigens.