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Farnesol, a Potential Efflux Pump Inhibitor in Mycobacterium smegmatis

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Author(s): Jing Jin | Ji-Yu Zhang | Na Guo | Hui Sheng | Lei Li | Jun-Chao Liang | Xue-Lin Wang | Yang Li | Ming-Yuan Liu | Xiu-Ping Wu | Lu Yu

Journal: Molecules
ISSN 1420-3049

Volume: 15;
Issue: 11;
Start page: 7750;
Date: 2010;
Original page

Keywords: farnesol | inhibitor | efflux pump | Mycobacterium smegmatis

ABSTRACT
The active multidrug efflux pump (EP) has been described as one of the mechanisms involved in the natural drug resistance of bacteria, such as mycobacteria. As a result, the development of efflux pumps inhibitors (EPIs) is an important topic. In this study, a checkerboard synergy assay indicated that farnesol both decreased the minimum inhibitory concentration (MIC) of ethidium bromide (EtBr) 8-fold against Mycobacterium smegmatis (M. smegmatis) mc2155 ATCC 700084 when incorporated at a concentration of 32 μg/mL (FICI = 0.625) and decreased MIC 4-fold at 16 μg/mL (FICI = 0.375). Farnesol also showed synergism when combined with rifampicin. A real-time 96-well plate fluorometric method was used to assess the ability of farnesol to inhibit EPs in comparison withfour positive EPIs: chlorpromazine, reserpine, verapamil, and carbonyl cyanide m-chlorophenylhydrazone (CCCP). Farnesol significantly enhanced the accumulation of EtBr and decreased the efflux of EtBr in M. smegmatis; these results suggest that farnesol acts as an inhibitor of mycobacterial efflux pumps.
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