The AraC-family regulator GadX enhances multidrug resistance in Escherichia coli by activating expression of mdtEF multidrug efflux genes
The AraC-family regulator GadX enhances multidrug resistance in Escherichia coli by activating expression of mdtEF multidrug efflux genes
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DOI：
10.1007/s10156-007-0575-y
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发表时间：
2008-02-01
影响因子：
2.2
通讯作者：
Yamaguchi, Akihito
中科院分区：
文献类型：
--
作者：
Nishino, Kunihiko;Senda, Yasuko;Yamaguchi, Akihito
多药外排泵有助于大肠杆菌对许多抗生素和杀生物剂的耐药性。在这里，我们报道了AraC家族调节剂GadX增加了大肠杆菌的多药耐药性。大肠杆菌通过激活MdtEF外排泵。筛选基因组DNA的随机片段以增加β-内酰胺抗性的能力导致分离含有gadX的质粒，其编码耐酸性的调节剂。当过表达时，gadX显著增加了E.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6 G和十二烷基硫酸钠的耐受性。通过删除多功能外膜通道基因tolC，完全抑制了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。实时荧光定量PCR结果显示，GadX激活了mdtEF的表达，但没有激活其他药物外排泵的表达。杆菌mdtEF的缺失完全抑制GadX介导的多药耐药。我们的研究结果表明，GadX调节剂，除了其在耐酸性中的作用，增加了大肠杆菌的多药耐药性。大肠杆菌的MdtEF多药外排泵。
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.