title: The Pleiotropic Antibacterial Mechanisms of Ursolic Acid against Methicillin-Resistant Staphylococcus aureus (MRSA).
abstract: (1) BACKGROUND: Several triterpenoids were found to act synergistically with classes of antibiotic, indicating that plant-derived chemicals have potential to be used as therapeutics to enhance the activity of antibiotics against multidrug-resistant pathogens. However, the mode of action of triterpenoids against bacterial pathogens remains unclear. The objective of this study is to evaluate the interaction between ursolic acid against methicillin-resistant Staphylococcus aureus (MRSA); (2) METHODS: The ability of ursolic acid to damage mammalian and bacterial membranes was examined. The proteomic response of methicillin-resistant S. aureus in ursolic acid treatment was investigated using two-dimensional (2D) proteomic analysis; (3) RESULTS: Ursolic acid caused the loss of staphylococcal membrane integrity without hemolytic activity. The comparison of the protein pattern of ursolic acid-treated and normal MRSA cells revealed that ursolic acid affected a variety of proteins involved in the translation process with translational accuracy, ribonuclease and chaperon subunits, glycolysis and oxidative responses; (4) CONCLUSION: The mode of action of ursolic acid appears to be the influence on the integrity of the bacterial membrane initially, followed by inhibition of protein synthesis and the metabolic pathway. These findings reflect that the pleiotropic effects of ursolic acid against MRSA make it a promising antibacterial agent in pharmaceutical research.
authors.affiliation: Research Center for Biodiversity, China Medical University, Taichung 40402, Taiwan. wangchaomin@mail.cmu.edu.tw.
authors.forename: Chao-Min
authors.initials: CM
authors.lastname: Wang
authors.affiliation: Research Center for Biodiversity, China Medical University, Taichung 40402, Taiwan. ah_giu@yahoo.com.tw.
authors.forename: Yun-Lian
authors.initials: YL
authors.lastname: Jhan
authors.affiliation: Research Center for Biodiversity, China Medical University, Taichung 40402, Taiwan. csungjay@yahoo.com.tw.
authors.forename: Shang-Jie
authors.initials: SJ
authors.lastname: Tsai
authors.affiliation: Research Center for Biodiversity, China Medical University, Taichung 40402, Taiwan. choumasa@mail.cmu.edu.tw.
authors.forename: Chang-Hung
authors.initials: CH
authors.lastname: Chou
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D015394:Molecular Structure; D014176:Protein Biosynthesis / Q000187:drug effects; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods; D012756:Sheep; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: methicillin-resistant Staphylococcus aureus (MRSA); two-dimensional gel electrophoresis (2DE); ursolic acid