Resveratrol controls Escherichia coli growth by inhibiting the AcrAB-TolC efflux pump

Resveratrol (RSV), a phytoalexin found in grapes and other plants, is known to have antibacterial effects against Escherichia coli. In this study, we aimed to identify the target gene(s) for the antibacterial activity of RSV in E. coli. Using a DNA microarray, we found that exposure to RSV led to changes in the expression levels of iron metabolism genes, and those involved in drug response and respiration. Thus, we measured the antibacterial activity of RSV against 14 E. coli mutants with deletions in genes involved in these processes and found over fourfold higher growth inhibition in strains defective in AcrAB-TolC pump-related genes. Among the three genes encoding the AcrAB-TolC pump, tolC expression was most decreased by RSV. To determine if tolC was a direct target of RSV, we constructed both a tolC promoter-reporter gene vector and a tolC-complementation vector and transformed them into a tolC deletion mutant. RSV susceptibility and Nile red efflux tests were performed with the transformants. RSV significantly decreased tolC-promoter activity and tolC expression, thereby retarding activity of the AcrAB-TolC drug efflux complex, which may promote RSV's antibacterial activity in E. coli.