title: Ellagic acid derivatives from Rubus ulmifolius inhibit Staphylococcus aureus biofilm formation and improve response to antibiotics.
abstract: BACKGROUND
  Biofilms contribute to the pathogenesis of many forms of Staphylococcus aureus infection. Treatment of these infections is complicated by intrinsic resistance to conventional antibiotics, thus creating an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections.
  
  
  RESULTS
  This study demonstrates that a botanical natural product composition (220D-F2) rich in ellagic acid and its derivatives can limit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility. The source of this composition is Rubus ulmifolius Schott. (Rosaceae), a plant used in complementary and alternative medicine in southern Italy for the treatment of skin and soft tissue infections. All S. aureus clonal lineages tested exhibited a reduced capacity to form a biofilm at 220D-F2 concentrations ranging from 50-200 µg/mL, which were well below the concentrations required to limit bacterial growth (530-1040 µg/mL). This limitation was therapeutically relevant in that inclusion of 220D-F2 resulted in enhanced susceptibility to the functionally-distinct antibiotics daptomycin, clindamycin and oxacillin. Testing with kidney and liver cell lines also demonstrated a lack of host cell cytotoxicity at concentrations of 220D-F2 required to achieve these effects.
  
  
  CONCLUSIONS
  These results demonstrate that extract 220D-F2 from the root of Rubus ulmifolius can be used to inhibit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility without toxic effects on normal mammalian cells. Hence, 220D-F2 is a strong candidate for development as a botanical drug for use in the prevention and treatment of S. aureus biofilm-associated infections.
authors.affiliation: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Cassandra L
authors.initials: CL
authors.lastname: Quave
authors.forename: Miriam
authors.initials: M
authors.lastname: Estévez-Carmona
authors.forename: Cesar M
authors.initials: CM
authors.lastname: Compadre
authors.forename: Gerren
authors.initials: G
authors.lastname: Hobby
authors.forename: Howard
authors.initials: H
authors.lastname: Hendrickson
authors.forename: Karen E
authors.initials: KE
authors.lastname: Beenken
authors.forename: Mark S
authors.initials: MS
authors.lastname: Smeltzer
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019072:Antibiotic Prophylaxis; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development*; D001681:Biological Assay; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D005591:Chemical Fractionation; D002853:Chromatography, Liquid; D004610:Ellagic Acid / Q000737:chemistry / Q000494:pharmacology*; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D008826:Microbial Sensitivity Tests; D018613:Microscopy, Confocal; D010936:Plant Extracts / Q000737:chemistry; D027824:Rosaceae / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D010936:Plant Extracts; D004610:Ellagic Acid