Mta, a global MerR-type regulator of the Bacillus subtilis multidrug-efflux transporters
Mta, a global MerR-type regulator of the Bacillus subtilis multidrug-efflux transporters
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DOI：
10.1046/j.1365-2958.1999.01301.x
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发表时间：
1999-03-01
影响因子：
3.6
通讯作者：
Neyfakh, AA
中科院分区：
文献类型：
--
作者：
Baranova, NN;Danchin, A;Neyfakh, AA
关于细菌表达的多药外排转运蛋白的天然功能知之甚少。虽然被鉴定为主动将外源毒素从细胞中挤出的膜蛋白，但它们实际上可能参与尚未鉴定的特定天然底物的运输。枯草芽孢杆菌的两个高度相似的多药转运蛋白Bmr和Fit的表达分别受特定的转录激活因子BmrR和BltR的调控，它们响应于不同的诱导分子，从而表明这两个转运蛋白的不同功能。在这里，我们描述了一种替代的调节机制，它涉及一个全球性的转录激活因子，Mta，细菌调控蛋白的MerR家族的成员。单独表达的Mta的N-末端DNA结合结构域直接与bmr和bit的启动子相互作用并诱导这些基因的转录。此外，该结构域刺激Mta基因本身和至少一个编码假定膜蛋白的基因Mta fK的表达。这些结果和Mta与变铅青链霉菌的硫链丝菌素诱导的蛋白TipA的相似性强烈地表明Mta是一种自体控制的全局转录调节因子，其活性由尚未鉴定的诱导物刺激，通过去除C-末端诱导剂结合结构域来模拟这种刺激。Bmr和Bit都由这个调节器控制的事实表明，它们的一些功能是相同的，或者至少是相关的。进一步分析MTA介导的调节可能揭示B中多药转运体系统的天然功能。枯草芽孢杆菌和作为其他细菌中的类似系统的范例。
Little is known about the natural functions of multidrug-efflux transporters expressed by bacteria. Although identified as membrane proteins actively extruding exogenous toxins from the cell, they may actually be involved in the transport of as yet unidentified specific natural substrates. The expression of two highly similar multidrug transporters of Bacillus subtilis, Bmr and Fit, is regulated by specific transcriptional activators, BmrR and BltR, respectively, which respond to different inducer molecules, thus suggesting distinct functions for the two transporters. Here, we describe an alternative mechanism of regulation, which involves a global transcriptional activator, Mta, a member of the MerR family of bacterial regulatory proteins. The individually expressed N-terminal DNA-binding domain of Mta interacts directly with the promoters of bmr and bit and induces transcription of these genes. Additionally, this domain stimulates the expression of the mta gene itself and at least one more gene, ydfK, which encodes a hypothetical membrane protein, These results and the similarity of Mta to the thiostrepton-induced protein TipA of Streptomyces lividans strongly suggest that Mta is an autogenously controlled global transcriptional regulator, whose activity is stimulated by an as yet unidentified inducer, This stimulation is mimicked by the removal of the C-terminal inducer-binding domain. The fact that both Bmr and Bit are controlled by this regulator demonstrates that some of their functions are either identical or, at least, related. Further analysis of Mta-mediated regulation may reveal the natural function of the system of multidrug transporters in B. subtilis and serve as a paradigm for similar systems in other bacteria.