Role of the AraC–XylS family regulator YdeO in multi-drug resistance of Escherichia coli
Role of the AraC–XylS family regulator YdeO in multi-drug resistance of Escherichia coli
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DOI：
10.1038/ja.2009.23
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发表时间：
2009-03
期刊：
影响因子：
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通讯作者：
K. Nishino;Y. Senda;Mitsuko Hayashi-Nishino;A. Yamaguchi
中科院分区：
文献类型：
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作者：
K. Nishino;Y. Senda;Mitsuko Hayashi-Nishino;A. Yamaguchi
多药外排泵有助于大肠杆菌对许多抗生素和杀菌剂产生耐药性。在这项研究中，我们报告了 AraC-XylS 家族调节剂 YdeO 通过激活 MdtEF 外排泵来增加大肠杆菌的多药耐药性。对基因组 DNA 随机片段筛选其增强 β-内酰胺抗性的能力，分离出含有 ydeO 的质粒，该质粒编码抗酸性调节剂。当过表达时，ydeO 显着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。通过删除多功能外膜通道基因tolC，可以完全抑制ydeO过表达引起的耐药性增加。 TolC 与不同的药物流出泵相互作用。实时定量 PCR 显示，YdeO 仅激活大肠杆菌中的 mdtEF 表达，而不会激活其他药物流出泵。 mdtEF 的缺失完全抑制了 YdeO 介导的多药耐药性。 YdeO 增强大肠杆菌中 MdtEF 依赖性药物流出活性。我们的结果表明，YdeO 调节剂除了在耐酸性中发挥作用外，还通过激活 MdtEF 多药外排泵来增加大肠杆菌的多药耐药性。
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 β-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.