title: Gramicidin D enhances the antibacterial activity of fluoride.
abstract: Fluoride is a toxic anion found in many natural environments. One of the major bacterial defenses against fluoride is the cell envelope, which limits passage of the membrane-impermeant fluoride anion. Accordingly, compounds that enhance the permeability of bacterial membranes to fluoride should also enhance fluoride toxicity. In this study, we demonstrate that the pore-forming antibiotic gramicidin D increases fluoride uptake in Bacillus subtilis and that the antibacterial activity of this compound is potentiated by fluoride. Polymyxin B, another membrane-targeting antibiotic with a different mechanism of action, shows no such improvement. These results, along with previous findings, indicate that certain compounds that destabilize bacterial cell envelopes can enhance the toxicity of fluoride.
authors.affiliation: Department of Chemistry, Yale University, P.O. Box 208107, New Haven, CT 06520, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Nelson
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, P.O. Box 208103, New Haven, CT 06520, USA.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, P.O. Box 208103, New Haven, CT 06520, USA.|Department of Molecular Biophysics and Biochemistry, Yale University, P.O. Box 208103, New Haven, CT 06520, USA.|Howard Hughes Medical Institute.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Breaker
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005459:Fluorides / Q000737:chemistry / Q000494:pharmacology*; D006096:Gramicidin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D006096:Gramicidin; D005459:Fluorides
keywords: Antibiotic; Bacillus subtilis; Fluoride reporter; Polymyxin B; Riboswitch