Staphylococcus aureus is a common upper respiratory tract (URT) pathobiont with high carriage rates in the upper airway disease chronic rhinosinusitis (CRS). CRS is associated with increased prevalence and abundance of S. aureus, and S. aureus-secreted toxins are implicated in CRS pathogenesis. Conversely, in CRS disease, the abundance of non-pathogenic commensal species has been observed to decline, leading to microbial dysbiosis that contributes to persistent inflammation. Here, we investigated possible mechanisms S. aureus could employ to outcompete commensal organisms and contribute to establishing the S. aureus-dominant microbiome found in individuals with CRS. We performed a targeted screen to identify S. aureus-secreted factors that affect the growth and aggregation of a URT commensal bacterium, Corynebacterium pseudodiphtheriticum, which is negatively correlated with S. aureus in CRS. S. aureus cell-free conditioned media prevented C. pseudodiphtheriticum aggregation; however, anti-aggregation activity was significantly reduced in S. aureus mutants lacking a functional accessory gene regulator (agr) quorum-sensing system, phenol-soluble modulin (PSM) transporters, and the PSM toxin δ-toxin. Addition of purified recombinant δ-toxin peptide or a related PSM, PSMα3, inhibited C. pseudodiphtheriticum aggregation and induced dispersal of aggregates. Recombinant δ-toxin also reduced C. pseudodiphtheriticum adherence and aggregation on human nasal epithelial cells. PSMs are known to play a role in biofilm structure and remodeling in staphylococci, and here, we demonstrate that PSMs have activity against other bacteria. These results identify a novel mechanism by which S. aureus can disrupt the commensal lifestyle of microbes that inhabit the same upper respiratory niche via secreted PSM toxins.IMPORTANCEIncreased Staphylococcus aureus abundance and microbial dysbiosis are associated with the pathogenesis of chronic rhinosinusitis disease. Here, we show that S. aureus δ-toxin, a secreted phenol-soluble modulin (PSM) toxin, can inhibit the ability of commensal Corynebacterium species to aggregate, adhere to, and grow in association with human nasal epithelial cells. PSMs are known to play a key role in the S. aureus biofilm life cycle, regulating S. aureus biofilm structure and detachment; however, a role for these toxins in modifying biofilm and aggregate structures of other bacteria has not been previously demonstrated. These results suggest a potential mechanism for S. aureus to establish dominance in the upper respiratory tract microbiome in disease through direct antagonism of commensal microbes with PSM toxins.
Huffines et al. (Thu,) studied this question.