543 Chronic wound environment shapes virulence of human commensal bacteria

Staphylococcus epidermidis is one of the most abundant skin-commensal known to modulate cutaneous immune response. Emerging evidence suggests S. epidermidis isolates from healthy skin improve barrier integrity and response to wounding. However, S. epidermidis could also carry a reservoir of antimicrobial resistance genes(ARGs), adding this microbe to the list of “accidental” pathogens. Hence, we aimed to characterize S. epidermidis isolates from healthy skin and chronic wounds (CW) to evaluate their virulence potential and effect on wound healing. Shotgun metagenomic sequencing was performed to analyze presence of ARG and virulence genes 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 components of the extracellular matrix (ECM) were performed. Human ex vivo wound model was used to assess the effect of S. epidermidis isolates on healing. Results pointed to the prevalence of ARG in S. epidermidis isolates from CW associated with gentamicin, ampicillin, erythromycin, norfloxacin, tetracycline, and trimethoprim resistance. This was functionally confirmed, chronic wound isolates showed higher minimal inhibitory concentration (MIC) values for these antibiotics and for benzalkonium chloride, a widely used disinfectant. All CW strains exhibited a higher ability to bind to ECM components compared to healthy skin strains. This feature of CW 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 CW isolates in the wound bed suggesting the strong ability of in vivo biofilm formation. Our study suggests that CW 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 CW.