Induction mechanism of a xenobiotic exporter MdtEF by N-acetyl-D-glucosamine

It is known that bacterial xenobiotic exporters contribute to the resistance against several toxic compounds. MdtEF is a RND-type xenobiotic exporter of Escherichia coli that extrudes beta-lactams, dyes, antiseptics, and detergents. MdtEF confers high-level xenobiotic resistance when it is expressed, but is hardly expressed under the normal condition. In this study, we screened compounds that induce mdtEF transcription. As a result, we found that N-acetyl-D-glucosamine (GIcNAc), a component of peptidoglycan, induces mdtEF expression. GIcNAc increases the survival rate of Escherichia coli in the presence of rhodamine 6G. The regulatory pathway induced by GIcNAc was neither via EvgSA two component signal transduction system nor transcriptional regulators such as YdeO and GadX GIcNAc is imported by NagE and ManXYZ phosphotransferase system. In nagE deletion mutant, transcription of mdtEF was not up-regulated when GIcNAc was supplied. Therefore, it is clear that GIcNAc functions in the cytoplasm to induce mdtEF transcription.