Structure Elucidation Of Ursene And Oleanene Derivatives From Castanea Sativa (European Chestnut) That Inhibit Staphylococcus Aureus Virulence And Pathogenesis

Abstract

Alarming trends in the spread of antibiotic resistance among pathogens, including Staphylococcus aureus, have pushed mankind toward what has been coined as the “post-antibiotic era.” Therefore, an indirect therapy is proposed, quorum quenching. Investigation of botanical folk medicines used in the Mediterranean for the treatment of skin and soft tissue infections identified Castanea sativa (European Chestnut) for its potential antibacterial activity. This work demonstrates the quorum sensing inhibitory activity of a methanolic C. sativa leaf extract against all S. aureus accessory gene regulator (agr) alleles (IC50 1.56 – 25 µg mL-1). The extract is nontoxic to human keratinocytes and does not inhibit the growth of S. aureus or skin commensal bacteria. The bioactivity guided fractionation identified several compounds with ursene (1) and oleanene (2) backbones as the active compounds. The isolation and complete structure elucidation was performed using LC FT-MS and a suite of 1D and 2D NMR experiments.