SummaryOur comprehensive expression cloning studies previously revealed that 20 intrinsic xenobiotic exporter systems are encoded in the Escherichia coli chromosome, but most of them are not expressed under normal conditions. In this study, we investigated the compounds that induce the expression of these xenobiotic exporter genes, and found that indole induces a variety of xenobiotic exporter genes including acrD , acrE , cusB , emrK , mdtA , mdtE and yceL . Indole treatment of E. coli cells confers rhodamine 6G and SDS resistance through the induction of mdtEF and acrD gene expression respectively. The induction of mdtE by indole is independent of the EvgSA twocomponent signal transduction system that regulates the mdtE gene, but mediated by GadX. On the other hand, the induction of acrD and mdtA was mediated by BaeSR and CpxAR, two-component systems. Interestingly, CpxAR system-mediated induction required intrinsic baeSR genes, whereas BaeSR-mediated induction was observed in the cpxAR gene-deletion mutant. BaeR and CpxR directly bound to different sequences of the acrD and mdtA promoter regions. These observations indicate that BaeR is a primary regulator, and CpxR enhances the effect of BaeR.

The response regulator EvgA controls expression of multiple genes conferring antibiotic resistance in Escherichia coli (K. Nishino and A. Yamaguchi, J. Bacteriol. 184:2319-2323, 2002). To understand the whole picture of EvgA regulation, DNA macroarray analysis of the effect of EvgA overproduction was performed. EvgA activated genes related to acid resistance, osmotic adaptation, and drug resistance

The expression of MdtEF, a multidrug exporter in Escherichia coli, is positively controlled through multiple signaling pathways, but little is known about signals that induce MdtEF expression. In this study, we investigated compounds that induce the expression of the mdtEF genes and found that out of 20 drug exporter genes in E. coli, the expression of mdtEF is greatly induced by N-acetyl-D-glucosamine (GlcNAc). The induction of mdtEF by GlcNAc is not mediated by the evgSA, ydeO, gadX, and rpoS signaling pathways that have been known to regulate mdtEF expression. On the other hand, deletion of the nagE gene, encoding the phosphotransferase (PTS) system for GlcNAc, prevented induction by GlcNAc. The induction of mdtEF by GlcNAc was also greatly inhibited by the addition of cyclic AMP (cAMP) and completely abolished upon deletion of the cAMP receptor protein gene (crp). Other PTS sugars, glucose and Dglucosamine, also induced mdtEF gene expression. These results suggest that mdtEF expression is stimulated through catabolite control.