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Molecules 2010, 15(11), 7750-7762; doi:10.3390/molecules15117750
Article

Farnesol, a Potential Efflux Pump Inhibitor in Mycobacterium smegmatis

1,†, 2,†, 3,†, 4, 1, 1, 1, 1, 1, 1,*  and 1,*
1 Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, 130062, China 2 Key and Open Laboratory of Veterinary Pharmaceutical Engineering, Lanzhou Institute of Animal Science and Veterinary Pharmaceutics, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China 3 Laboratory of Nutrition and Functional Food, Jilin University, Changchun, 130062, China 4 The First Hospital of Jilin University, Jilin University, Changchun, 130021, China These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 1 September 2010 / Revised: 2 October 2010 / Accepted: 25 October 2010 / Published: 29 October 2010
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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.
Keywords: farnesol; inhibitor; efflux pump; Mycobacterium smegmatis farnesol; inhibitor; efflux pump; Mycobacterium smegmatis
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Jin, J.; Zhang, J.-Y.; Guo, N.; Sheng, H.; Li, L.; Liang, J.-C.; Wang, X.-L.; Li, Y.; Liu, M.-Y.; Wu, X.-P.; Yu, L. Farnesol, a Potential Efflux Pump Inhibitor in Mycobacterium smegmatis. Molecules 2010, 15, 7750-7762.

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