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The phenolic diterpene totarol had good antimicrobial activity against effluxing strains ofStaphylococcus 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 overexpressednorA was created to separate antimicrobial from efflux inhibitory activity. Totarol reduced ethidium efflux from this strain by 50% at 15 μM (1/4× 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.

The Phenolic Diterpene Totarol Inhibits Multidrug Efflux Pump Activity in Staphylococcus aureus