Farnesol, a potential efflux pump inhibitor in Mycobacterium smegmatis.
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 with four 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.
Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China.
Jing
J
Jin
Ji-Yu
JY
Zhang
Na
N
Guo
Hui
H
Sheng
Lei
L
Li
Jun-Chao
JC
Liang
Xue-Lin
XL
Wang
Yang
Y
Li
Ming-Yuan
MY
Liu
Xiu-Ping
XP
Wu
Lu
L
Yu
D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D002746:Chlorpromazine / Q000494:pharmacology; D005204:Farnesol / Q000494:pharmacology*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D020102:Mycobacterium smegmatis / Q000187:drug effects* / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D009570:Nitriles; C100076:mesoxalonitrile; D005204:Farnesol; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D012110:Reserpine; D014700:Verapamil; D002746:Chlorpromazine