Staphylococcus aureus phenol-soluble modulins have dispersal and anti-aggregation activity towards corynebacteria

Abstract

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.