The phenolic diterpene totarol inhibits multidrug efflux pump activity in Staphylococcus aureus

Antimicrob Agents Chemother. 2007 Dec;51(12):4480-3. doi: 10.1128/AAC.00216-07. Epub 2007 Jul 30.


The phenolic diterpene totarol had good antimicrobial activity against effluxing strains of Staphylococcus aureus. Subinhibitory concentrations reduced the MICs of selected antibiotics, suggesting that it may also be an efflux pump inhibitor (EPI). A totarol-resistant mutant that overexpressed norA was created to separate antimicrobial from efflux inhibitory activity. Totarol reduced ethidium efflux from this strain by 50% at 15 microM (1/4x MIC), and combination studies revealed marked reductions in ethidium MICs. These data suggest that totarol is a NorA EPI as well as an antistaphylococcal antimicrobial agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / metabolism*
  • Diterpenes / chemistry
  • Diterpenes / pharmacology*
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / metabolism


  • Abietanes
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Diterpenes
  • Multidrug Resistance-Associated Proteins
  • NorA protein, Staphylococcus
  • totarol