Role of the AraC-XylS family regulator YdeO in multi-drug resistance of Escherichia coli

Multi-drug efflux pumps contribute to the resistance of Escherichia coli to many antibiotics and biocides. In this study, we report that the AraC-XylS family regulator YdeO increases the multi-drug resistance of E. coli through activation of the MdtEF efflux pump. Screening of random fragments of genomic DNA for their ability to increase beta-lactam resistance led to the isolation of a plasmid containing ydeO, which codes for the regulator of acid resistance. When overexpressed, ydeO significantly increased the resistance of the E. coli strain to oxacillin, cloxacillin, nafcillin, erythromycin, rhodamine 6G and sodium dodecyl sulfate. The increase in drug resistance caused by ydeO overexpression was completely suppressed by deleting the multifunctional outer membrane channel gene tolC. TolC interacts with different drug efflux pumps. Quantitative real-time PCR showed that YdeO activated only mdtEF expression and none of the other drug efflux pumps in E. coli. Deletion of mdtEF completely suppressed the YdeO-mediated multi-drug resistance. YdeO enhances the MdtEF-dependent drug efflux activity in E. coli. Our results indicate that the YdeO regulator, in addition to its role in acid resistance, increases the multi-drug resistance of E. coli by activating the MdtEF multi-drug efflux pump. The Journal of Antibiotics (2009) 62, 251-257; doi:10.1038/ja.2009.23; published online 27 March 2009