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

Eileen C. J. Smith; Glenn W. Kaatz; Susan M. Seo; Neale Wareham; Elizabeth M. Williamson; Simon Gibbons

doi:10.1128/AAC.00216-07

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

Eileen C. J. Smith, Glenn W. Kaatz, Susan M. Seo, Neale Wareham, Elizabeth M. Williamson, Simon Gibbons

Research output: Contribution to journal › Article › peer-review

108 Citations (SciVal)

Abstract

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 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.

Original language	English
Pages (from-to)	4480-4483
Number of pages	4
Journal	Antimicrobial Agents and Chemotherapy
Volume	51
Issue number	12
DOIs	https://doi.org/10.1128/AAC.00216-07
Publication status	Published - 1 Dec 2007

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10.1128/AAC.00216-07

https://AAC.asm.org/content/51/12/4480

Cite this

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abstract = "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 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.",

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AU - Kaatz, Glenn W.

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AU - Wareham, Neale

AU - Williamson, Elizabeth M.

AU - Gibbons, Simon

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AB - 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 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.

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