title: Asiatic acid and corosolic acid enhance the susceptibility of Pseudomonas aeruginosa biofilms to tobramycin.
abstract: Asiatic acid and corosolic acid are two natural products identified as biofilm inhibitors in a biofilm inhibition assay. We evaluated the activities of these two compounds on Pseudomonas aeruginosa biofilms grown in rotating disk reactors (RDRs) in combination with tobramycin and ciprofloxacin. To determine the ruggedness of our systems, the antibiotic susceptibilities of these biofilms were assessed with tobramycin and ciprofloxacin. The biofilm bacteria produced in the RDR were shown to display remarkable tolerance to 10 mug/ml of ciprofloxacin, thus mimicking the tolerance observed in recalcitrant bacterial infections. These studies further demonstrate that a nonmucoid strain of P. aeruginosa can form a biofilm that tolerates ciprofloxacin at clinically relevant concentrations. Neither asiatic acid nor corosolic acid reduced the viable cell density of P. aeruginosa biofilms. However, both compounds increased the susceptibility of biofilm bacteria to subsequent treatment with tobramycin, suggesting asiatic acid and corosolic acid to be compounds that potentiate the activity of antibiotics. A similar statistical interaction was observed between ciprofloxacin and subsequent treatment with tobramycin.
authors.affiliation: Sequoia Sciences Inc, Saint Louis, MO 63114, USA. egaro@sequoiasciences.com
authors.forename: Eliane
authors.initials: E
authors.lastname: Garo
authors.forename: Gary R
authors.initials: GR
authors.lastname: Eldridge
authors.forename: Matt G
authors.initials: MG
authors.lastname: Goering
authors.forename: Elinor
authors.initials: E
authors.lastname: DeLancey Pulcini
authors.forename: Martin A
authors.initials: MA
authors.lastname: Hamilton
authors.forename: John W
authors.initials: JW
authors.lastname: Costerton
authors.forename: Garth A
authors.initials: GA
authors.lastname: James
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000502:physiology; D018441:Biofilms / Q000187:drug effects*; D002939:Ciprofloxacin / Q000494:pharmacology; D004357:Drug Synergism; D008826:Microbial Sensitivity Tests; D053978:Pentacyclic Triterpenes; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology; D014031:Tobramycin / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C062886:CysB protein, Bacteria; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D002939:Ciprofloxacin; C017032:asiatic acid; C113861:corosolic acid; D014031:Tobramycin