Staphylococcus aureus Phenol-Soluble Modulins Mediate Interspecies Competition with Upper Respiratory Commensal Bacteria

bioRxiv [Preprint]. 2024 Sep 25:2024.09.24.614779. doi: 10.1101/2024.09.24.614779.

Abstract

In chronic rhinosinusitis (CRS) disease, microbial dysbiosis is considered a key contributor to inflammation and pathogenicity, with increased prevalence of upper respiratory tract (URT) pathogens concomitant with decreased abundance of commensal species. Staphylococcus aureus is a common URT pathobiont associated with higher carriage rates in CRS. S. aureus secreted toxins are implicated in CRS pathogenesis, and toxins and antibodies to S. aureus secreted factors have been observed in tissue from CRS subjects. CRS disease severity is positively correlated with immune reactivity to S. aureus proteins. Prior studies have examined polymicrobial interactions between S. aureus and URT commensals, however, no studies to date have described possible methods employed by S. aureus to outcompete commensals leading to a S. aureus- dominant microbiome as seen in CRS. This study addresses this gap in knowledge by characterizing how a CRS-associated secreted toxin from S. aureus can inhibit aggregation in commensal URT species. Using a model URT commensal, Corynebacterium pseudodiphtheriticum , we identified a CRS-associated secreted protein from S. aureus , δ-toxin (Hld), that can inhibit C. pseudodiphtheriticum aggregation at biologically relevant concentrations. Furthermore, we observed recombinant δ-toxin reduces C. pseudodiphtheriticum adherence and aggregation on human nasal epithelial cells in an air-liquid interface cell culture model. These results define a novel mechanism by which S. aureus can disrupt URT commensal lifestyles of microbial competitors, contributing to the establishment of microbial dysbiosis.

Importance: Microbial dysbiosis in the upper respiratory tract (URT) is associated with disease pathogenicity in chronic rhinosinusitis (CRS). There are significant links between Staphylococcus aureus and worse CRS outcomes, but no studies to date have demonstrated if S. aureus outcompetes other URT microbes through direct interactions. Here, we report that S. aureus δ-toxin, a secreted protein found in CRS patient tissue, can inhibit the ability of commensal bacteria to aggregate, adhere to, and grow in association with human nasal epithelial cells. These results suggest a potential mechanism for S. aureus to establish dominance in the URT microbiome through direct antagonism of commensals with a disease-associated toxin.

Publication types

  • Preprint