Transcriptional regulation of drug efflux genes by EvgAS, a two-component system in Escherichia coli
Transcriptional regulation of drug efflux genes by EvgAS, a two-component system in Escherichia coli
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DOI：
10.1099/mic.0.26460-0
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发表时间：
2003-10-01
期刊：
影响因子：
2.8
通讯作者：
Utsumi, R
中科院分区：
文献类型：
--
作者：
Eguchi, Y;Oshima, T;Utsumi, R
组氨酸激酶传感器的组成型活性突变体EvgS被发现赋予多药耐药（MDR）的acrA缺陷的大肠杆菌，表明双组分系统EvgAS和MDR系统的表达之间的关系。所观察到的MDR也依赖于外膜通道TolC。微阵列和S1定位分析表明，在这种组成型突变体EvgS的存在下，一些MDR基因的转录水平增加，包括药物外排基因emrKY、yhiUV、acrAB、mdfA和tolC。通过添加磷酸化的EvgA增加emrK的体外转录。然而，由激活的EvgS对tolC的转录激活依赖于EvgAS和PhoPQ（Mg2+响应性双组分系统），这与tolC启动子区域中调节剂PhoP的结合位点（PhoP盒）的存在一致。yhiUV的体外转录似乎还需要除EvgA之外的尚未鉴定的另外的转录因子。综上所述，我们提出MDR系统的表达是在一个复杂的调控网络下，包括作为主调节器的磷酸化EvgA。
A constitutively active mutant of histidine kinase sensor EvgS was found to confer multi-drug resistance (MDR) to an acrA-deficient Escherichia coli, indicating the relationship between the two-component system EvgAS and the expression of the MDR system. The observed MDR also depended on an outer-membrane channel, TolC. Microarray and S1 mapping assays indicated that, in the presence of this constitutive mutant EvgS, the level of transcription increased for some MDR genes, including the drug efflux genes emrKY, yhiUV, acrAB, mdfA and tolC. Transcription in vitro of emrK increased by the addition of phosphorylated EvgA. Transcription activation of tolC by the activated EvgS was, however, dependent on both EvgAS and PhoPQ (Mg2+-responsive two-component system), in agreement with the presence of the binding site (PhoP box) for the regulator PhoP in the tolC promoter region. Transcription in vitro of yhiUV also appears to require an as-yet-unidentified additional transcriptional factor besides EvgA. Taken together we propose that the expression of the MDR system is under a complex regulatory network, including the phosphorylated EvgA serving as the master regulator.