Gramicidin D enhances the antibacterial activity of fluoride

Bioorg Med Chem Lett. 2014 Jul 1;24(13):2969-2971. doi: 10.1016/j.bmcl.2014.03.061. Epub 2014 Mar 28.

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.

Keywords: Antibiotic; Bacillus subtilis; Fluoride reporter; Polymyxin B; Riboswitch.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacillus subtilis / drug effects
  • Dose-Response Relationship, Drug
  • Fluorides / chemistry
  • Fluorides / pharmacology*
  • Gramicidin / chemical synthesis
  • Gramicidin / chemistry
  • Gramicidin / pharmacology*
  • Microbial Sensitivity Tests
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Gramicidin
  • Fluorides