title: Antibacterial mechanism of fraxetin against Staphylococcus aureus.
abstract: Fraxetin is one of the main constituents of the traditional medicinal plant Fraxinus rhynchophylla. The inhibitory effect of fraxetin on various bacterial strains has been extensively reported, however, its mechanism of action on bacterial cells remains to be elucidated. In the present study, the antibacterial mechanism of fraxetin on Staphylococcus aureus was systematically investigated by examining its effect on cell membranes, protein synthesis, nucleic acid content and topoisomerase activity. The results indicated that fraxetin increased the permeability of the cell membrane but did not render it permeable to macromolecules, such as DNA and RNA. Additionally, the quantity of protein, DNA and RNA decreased to 55.74, 33.86 and 48.96%, respectively following treatment with fraxetin for 16 h. The activity of topoisomerase I and topoisomerase II were also markedly inhibited as fraxetin concentration increased. The result of the ultraviolet‑visible spectrophotometry demonstrated that the DNA characteristics exhibited a blue shift and hypochromic effect following treatment with fraxetin. These results indicated that fraxetin had a marked inhibitory effect on S.aureus proliferation. Further mechanistic studies showed that fraxetin could disrupt nucleic acid and protein synthesis by preventing topoisomerase from binding to DNA.
authors.affiliation: Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, College of Life Science, Liaoning Normal University, Dalian, Liaoning 116000, P.R. China.
authors.forename: Haiting
authors.initials: H
authors.lastname: Wang
authors.affiliation: Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, College of Life Science, Liaoning Normal University, Dalian, Liaoning 116000, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zou
authors.affiliation: Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, College of Life Science, Liaoning Normal University, Dalian, Liaoning 116000, P.R. China.
authors.forename: Kunpeing
authors.initials: K
authors.lastname: Xie
authors.affiliation: Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, College of Life Science, Liaoning Normal University, Dalian, Liaoning 116000, P.R. China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Xie
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis; D002462:Cell Membrane / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D004262:DNA Restriction Enzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D026942:DNA Topoisomerases / Q000378:metabolism; D004269:DNA, Bacterial / Q000096:biosynthesis; D050296:Microbial Viability / Q000187:drug effects; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D015183:Restriction Mapping; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism; D059003:Topoisomerase Inhibitors / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003374:Coumarins; D004269:DNA, Bacterial; D011500:Protein Synthesis Inhibitors; D059003:Topoisomerase Inhibitors; C105671:fraxetin; D004262:DNA Restriction Enzymes; D026942:DNA Topoisomerases