Concentration-dependent dual effects of bacterial nanocellulose on Staphylococcus aureus virulence and human dermal fibroblast function: implications for wound healing.

BACKGROUND: Antibiotic-resistant Staphylococcus aureus biofilms in skin wounds require therapies targeting both virulence and host repair. The wound biomaterial bacterial nanocellulose (BNC) has unclear effects on bacteria and host cells. We studied clinical S. aureus molecular epidemiology and BNC's concentration-dependent dual effects on bacterial virulence and human dermal fibroblast (HDF-1) inflammation, apoptosis, and proliferation. METHODS: 150 non-duplicate S. aureus isolates from skin/soft tissue infections were characterized (antibiogram, biofilm, virulence/resistance genes, MLVA). BNC MIC and sub-MIC (500 µg/mL) effects on hla, icaA, mecA expression, biofilm biomass, and oxacillin synergy were assessed. MTT assay identified non-cytotoxic BNC doses (10, 25, 50 µg/mL). In uninfected and infected HDF-1, RT-qPCR, ELISA, flow cytometry, and Western blot measured IL-6, IL-10, Bax, CDK1. RESULTS: Isolates showed high genetic diversity (Simpson index 0.94), 54% MRSA, universal biofilm formation, and complete icaB absence, suggesting ica-independent biofilms. BNC MIC was 1000 µg/mL. Sub-MIC (500 µg/mL) downregulated hla, icaA, mecA and reduced biofilm by 41%, but was cytotoxic (IC₅₀ 55 µg/mL). At non-cytotoxic doses (10-50 µg/mL), BNC downregulated IL-6 (0.42-fold), upregulated IL-10 (2.64-fold), Bax (2.12-fold), and CDK1 (1.84-fold), leading to increased early apoptosis (3.2% to 8.7%) and proliferation (1.7-fold). CONCLUSION: BNC exhibits opposing concentration-dependent effects: antivirulence at cytotoxic concentrations versus immunomodulatory and pro-regenerative at safe concentrations. Unmodified BNC is unsuitable as a direct antibacterial but promising as an immunomodulatory scaffold and drug delivery platform.