Chronic wound microenvironment shapes pathogenicity of human commensal isolates of Staphylococcus epidermidis

Staphylococcus epidermidis is one of the most abundant skin-resident bacteria, which provides benefits to host by modulating the cutaneous immune response. Emerging evidence suggests S. epidermidis isolates from healthy skin improve epithelial barrier integrity and response to wounding in a strain-specific manner. However, S. epidermidis could also carry a reservoir of antimicrobial resistance genes (ARGs), adding this microbe to the list of “accidental” pathogens.

Hence, this study aimed to characterize S. epidermidis isolates from healthy skin and chronic venous leg ulcers to evaluate their virulence potential and effect on wound healing.Shotgun metagenomic sequencing was performed to analyze presence of ARG in isolates from both environments.

Furthermore, antimicrobial susceptibility was tested using the microdilution method. To assess virulence traits of selected isolates, biofilm formation and adhesion to fibronectin and collagen, components of the host extracellular matrix (ECM) were performed. Finally, an ex vivo human skin wound model was used to assess the effect of S. epidermidis isolates on wound healing.Results of this study pointed to the prevalence of ARG in S. epidermidis isolates from chronic wounds associated with gentamicin, ampicillin, erythromycin, norfloxacin, tetracycline, and trimethoprim resistance.

This was functionally confirmed in microdilution assay as chronic wound isolates showed higher minimal inhibitory concentration (MIC) values for these relevant antibiotics and for benzalkonium chloride, a widely used disinfectant in wound care. All strains from chronic wounds exhibited a higher ability to bind to ECM components compared to strains from healthy skin. This feature of chronic wounds isolates correlates with their high biofilm formation potential in both in vitro and ex vivo assays. Infection of human ex vivo wounds showed increased accumulation of chronic wound isolates in the wound bed suggesting the strong ability of in vivo biofilm formation.

Our study suggests that chronic wound microenvironment influenced selection of S. epidermidis strains with prevalence of ARG and capacity to bind to ECM and form biofilm. Our data reflects the dangers of antibiotic overuse due to the frequency of antibiotic resistance and virulent potential of S. epidermidis strains found in chronic wounds, highlighting the importance of making informed decisions on chronic wound treatment.