Inhibition of the MRSA Biofilm Formation and Skin Antineoplastic Activity of Ethyl Acetate Roots and Aerial Parts Extracts from Geum urbanum L.

<b>Background:</b> The opportunistic pathogen <i>Staphylococcus aureus</i> causes skin and soft tissue infections that are associated with biofilm formation, and in immunocompromised patients can progress to surgical site infections, pneumonia, bacteremia, sepsis, and even death. Most antibiotics actively damage living, dividing cells on the surface of the biofilm, where there is a high concentration of nutrients and oxygen, while in the depths, where these factors are scarce, slowly growing cells remain. <b>Objectives:</b> The aim of our study was to evaluate the antibiofilm potential of ethyl acetate roots (EtOAcR) and aerial parts (EtOAcAP) extracts from the perennial Bulgarian plant <i>Geum urbanum</i> L. against methicillin-resistant <i>S. aureus</i> (MRSA) NBIMCC 8327. <b>Methods</b>: The effects of both extracts on the expression of biofilm-related genes, <i>ica</i>A and <i>ica</i>D, were investigated. The cytotoxicity of EtOAcR and EtOAcAP on A-375 (human melanoma), A-431 (epidermoid skin cancer) and HaCaT (normal keratinocytes) cell lines, and the induction of apoptosis were determined. Finally, the in vivo skin irritation potential of the most active extract was studied. <b>Results</b>: Both tested extracts inhibited biofilm formation at concentrations that did not affect bacterial growth. Interestingly, the expression of <i>ica</i>A and <i>ica</i>D was upregulated, although the biofilm development was inhibited 72.4-90.5% by EtOAcAP and 18.9-20.4% by EtOAcR at sub-MICs. EtOAcAP extract showed a more favorable cytotoxic profile on non-tumorigenic cells and stronger antineoplastic activity (IC₅₀ = 6.7-14.68 µg/mL) as compared to EtOAcR extract (IC₅₀ = 8.73-23.67 µg/mL). Therefore, a skin irritation test was performed with the EtOAcAP extract at ten-times higher concentrations than the minimum inhibitory one, and, resultantly, the primary irritation index was equal to zero (no skin irritation observed). <b>Conclusions</b>: The EtOAcAP extract was proven to be an effective antistaphylococcal agent with favorable skin tolerance. The extract showed strong antineoplastic activity and antibiofilm effect at sub-MICs, which outlines new prospects for its development as a natural product for specific skin applications in medical practice.