The phenolic diterpene totarol inhibits multidrug efflux pump activity in Staphylococcus aureus.
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.
Centre for Pharmacognosy and Phytotherapy, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
Eileen C J
EC
Smith
Glenn W
GW
Kaatz
Susan M
SM
Seo
Neale
N
Wareham
Elizabeth M
EM
Williamson
Simon
S
Gibbons
D045784:Abietanes; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism*; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism
D045784:Abietanes; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004224:Diterpenes; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C075040:NorA protein, Staphylococcus; C078548:totarol