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Antimicrob. Agents Chemother. doi:10.1128/AAC.01037-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Asiatic acid and corosolic acid enhance the susceptibility of P. aeruginosa biofilms to tobramycin

Sequoia Sciences Inc., 11199 Sorrento Valley Road, Suite H, San Diego, California 92121, Sequoia Sciences Inc. 1912 Innerbelt Center Drive, Saint Louis, Missouri 63114, Center for Biofilm Engineering, Montana State University, Bozeman, Montana 59717-3980

^* To whom correspondence should be addressed. Email: egaro{at}sequoiasciences.com. geldridge{at}sequoiasciences.com.

	Abstract

Asiatic acid and corosolic acid are two natural products identified as biofilm inhibitors in a biofilm inhibition assay. We evaluated the activity 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 susceptibility of these biofilms was assessed with tobramycin and ciprofloxacin. The biofilm bacteria produced in the RDR were shown to display remarkable tolerance to 10 µg/ml of ciprofloxacin, thus mimicking the tolerance observed in recalcitrant bacterial infections. These studies further demonstrate that a non-mucoid 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.