title: Farnesol decreases biofilms of Staphylococcus epidermidis and exhibits synergy with nafcillin and vancomycin.
abstract: Biofilm infections are frequently caused by Staphylococcus epidermidis, are resistant to antimicrobial agents, and adversely affect patient outcomes. We evaluated farnesol (FSL), the Candida quorum-sensing molecule, on S. epidermidis biofilms, in vitro and in vivo. We evaluated ED50, ED75, and ED90 (drug concentrations causing 50%, 75%, and 90% inhibition, respectively) of FSL and evaluated synergy with nafcillin and vancomycin. FSL's effects on morphology of S. epidermidis biofilms were analyzed using confocal microscopy and real-time changes using a bioluminescent strain of S. epidermidis, Xen 43. In mice, effects of FSL treatment on s.c. catheter biofilms; cultures of blood, kidney, and catheter and pericatheter tissues; and bioluminescence in strain Xen 43 were evaluated. FSL inhibited biofilms (ED50 ranged from 0.625 to 2.5 mM) and was synergistic with nafcillin and vancomycin at most combination ratios. FSL significantly decreased biovolume, substratum coverage, and mean thickness of S. epidermidis biofilms. In mice, FSL significantly decreased viable colony counts of S. epidermidis from blood, kidney, and catheter and pericatheter tissues and decreased Xen 43 bioluminescence. We confirmed the antibiofilm effects of FSL both in vitro and in vivo, in a bioluminescent strain and its synergy with antibiotics. FSL may be effective against clinical S. epidermidis biofilm infections.
authors.affiliation: Departments of Pediatrics, Texas Children's Hospital & Baylor College of Medicine, Houston, Texas 77030, USA. mohanv@bcm.edu
authors.forename: Mohan
authors.initials: M
authors.lastname: Pammi
authors.forename: Rong
authors.initials: R
authors.lastname: Liang
authors.forename: John M
authors.initials: JM
authors.lastname: Hicks
authors.forename: Jim
authors.initials: J
authors.lastname: Barrish
authors.forename: James
authors.initials: J
authors.lastname: Versalovic
mesh_terms: D000818:Animals; D018441:Biofilms / Q000187:drug effects*; D055499:Catheter-Related Infections / Q000188:drug therapy* / Q000382:microbiology; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005204:Farnesol / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D051379:Mice; D018613:Microscopy, Confocal; D009254:Nafcillin / Q000378:metabolism / Q000494:pharmacology; D013212:Staphylococcus epidermidis / Q000187:drug effects*; D014640:Vancomycin / Q000378:metabolism / Q000494:pharmacology
chemical_list: D005204:Farnesol; D009254:Nafcillin; D014640:Vancomycin