ETHNOPHARMACOLOGICAL RELEVANCE: Paulownia tomentosa Steud. (P. tomentosa) is a medium-sized tree traditionally used in Chinese folk medicine for the treatment of infectious diseases. It is a rich source of prenylated phenolic compounds that have been extensively studied for their promising biological activities. AIM OF THE STUDY: Due to the increasing development of antibiotic resistance, our study investigated plant-derived natural products from the fruits of P. tomentosa that could control Staphylococcus aureus infections with novel targets/modes of action and reduce antimicrobial resistance. MATERIALS AND METHODS: The ethanolic extract was fractionated and detected by liquid chromatography. The antistaphylococcal effects of the plant formulations were studied in detail in vitro by various biological methods, including microdilution methods for minimum inhibitory concentration (MIC), the checkerboard titration technique for synergy assay, fluorescence measurements for membrane disruption experiments, autoinducer-2-mediated bioassay for quorum sensing inhibition, and counting of colony-forming units for relative adhesion. Morphology was examined by transmission electron microscopy. RESULTS: Total ethanolic extract and chloroform fraction showed MICs of 128 and 32 μg/mL, respectively. Diplacol, diplacone, and 3'-O-methyl-5'-hydroxydiplacone inhibited S. aureus growth in the range of 8-16 μg/mL. Synergistic potential was shown in combination with mupirocin and fusidic acid. The ethanolic extract and the chloroform fraction destroyed the cell membranes by 91.61% and 79.46%, respectively, while the pure compounds were less active. The ethanolic extract and the pure compounds reduced the number of adhered cells to 47.33-10.26% compared to the untreated control. All tested plant formulations, except diplacone, inhibited quorum sensing of S. aureus. Transmission electron microscopy showed deformation of S. aureus cells. CONCLUSIONS: The products from the fruit of P. tomentosa showed antimicrobial properties against S. aureus alone and in combination with antibiotics. By affecting intracellular targets, geranylated flavonoids proposed novel approaches in the control of staphylococcal infections.

Department of Biotechnology and System Biology National Institute of Biology 1000 Ljubljana Slovenia

Department of Food Science and Technology Biotechnical Faculty University of Ljubljana 1000 Ljubljana Slovenia

Department of Molecular Pharmacy Faculty of Pharmacy Masaryk University 612 00 Brno Czech Republic

Department of Natural Drugs Faculty of Pharmacy Masaryk University 612 00 Brno Czech Republic

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