Abstract
Staphylococcus epidermidis is a resident skin commensal known to have beneficial effects such as modulating the cutaneous immune response and improving barrier integrity. However, it may act as a reservoir for antibiotic resistance genes (ABR) due to horizontal gene transfer and environmental selection pressure. Additionally, it has been found to have a similar abundance in chronic wounds as the well-studied pathogen S. aureus. Due to its prevalence in two distinct skin microenvironments, we aimed to characterize S. epidermidis isolates from healthy skin and chronic wounds to assess and compare their pathogenicity and effect on wound healing. S. epidermidis strains were isolated from healthy skin and chronic wounds, and shotgun metagenomic sequencing was performed to analyze the presence of ABR and biofilm-related genes. The genomic data was then correlated with in vitro assays for antimicrobial susceptibility, biofilm formation, and adhesion to fibronectin. A human ex vivo wound model was used to assess how S. epidermidis isolate infection affects healing and host immune response.
Our metagenome analysis revealed S. epidermidis isolates from the chronic wound environment had unique multi-drug resistance patterns. Additionally, chronic wound isolates showed higher antibiotic resistance in minimal inhibitory concentration (MIC) assays. Genomic data identified genes related to the production of biofilms and binding to host components in chronic wound isolates. This correlated with findings that compared to healthy skin isolates, chronic wound isolates have an increased binding to fibronectin, higher biofilm formation in vitro, and an increased accumulation in ex vivo wounds, suggesting the strong ability of in vivo biofilm formation. This research indicates that the chronic wound microenvironment influenced the selection of S. epidermidis strains with a more pathogenic phenotype, and echoes the previous research on the dangers of antibiotic overuse due to the multidrug resistance patterns and virulence potential of S. epidermidis strains in chronic wounds.