Nishino Kunihiko, Senda Yasuko, Yamaguchi Akihito
Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka, Japan.
J Infect Chemother. 2008 Feb;14(1):23-9. doi: 10.1007/s10156-007-0575-y. Epub 2008 Feb 24.
Multidrug efflux pumps contribute to the resistance of Escherichia coli to many antibiotics and biocides. Here, we report that the AraC-family regulator GadX increases multidrug resistance in E. coli through activation of the MdtEF efflux pump. Screening of random fragments of genomic DNA for ability to increase beta-lactam resistance led to the isolation of a plasmid containing gadX, which codes for the regulator of acid resistance. When overexpressed, gadX 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 gadX overexpression was completely suppressed by deleting the multifunctional outer membrane channel gene tolC. TolC interacts with different drug efflux pumps. Quantitative real-time polymerase chain reaction (PCR) showed that GadX activated the expression of mdtEF but none of the other drug efflux pumps in E. coli. Deletion of mdtEF completely suppressed GadX-mediated multidrug resistance. Our results indicate that the GadX regulator, in addition to its role in acid resistance, increases multidrug resistance in E. coli by activating the MdtEF multidrug efflux pump.
多药外排泵导致大肠杆菌对多种抗生素和杀菌剂产生耐药性。在此，我们报告阿拉伯糖操纵子家族调控因子GadX通过激活MdtEF外排泵增加大肠杆菌的多药耐药性。筛选基因组DNA随机片段增加β-内酰胺耐药性的能力，导致分离出一个含有gadX的质粒，该基因编码耐酸性调控因子。当gadX过表达时，它显著增加了大肠杆菌菌株对苯唑西林、氯唑西林、萘夫西林、红霉素、罗丹明6G和十二烷基硫酸钠的耐药性。通过缺失多功能外膜通道基因tolC，完全抑制了由gadX过表达引起的耐药性增加。TolC与不同的药物外排泵相互作用。定量实时聚合酶链反应（PCR）表明，GadX激活了mdtEF的表达，但未激活大肠杆菌中的其他药物外排泵。缺失mdtEF完全抑制了GadX介导的多药耐药性。我们的结果表明，GadX调控因子除了在耐酸性方面发挥作用外，还通过激活MdtEF多药外排泵增加大肠杆菌的多药耐药性。
