Baranova N N, Danchin A, Neyfakh A A
Center for Pharmaceutical Biotechnology (M/C 870), University of Illinois, Chicago 60607, USA.
Mol Microbiol. 1999 Mar;31(5):1549-59. doi: 10.1046/j.1365-2958.1999.01301.x.
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 Blt, 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 blt 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 Blt 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.
关于细菌表达的多药外排转运蛋白的天然功能，人们了解甚少。尽管它们被鉴定为能将外源性毒素主动排出细胞的膜蛋白，但实际上它们可能参与转运尚未确定的特定天然底物。枯草芽孢杆菌的两种高度相似的多药转运蛋白Bmr和Blt的表达，分别受特异性转录激活因子BmrR和BltR调控，这两种激活因子对不同的诱导分子有反应，因此表明这两种转运蛋白具有不同的功能。在此，我们描述了一种替代调控机制，该机制涉及一种全局转录激活因子Mta，它是细菌调控蛋白MerR家族的成员。单独表达的Mta的N端DNA结合结构域直接与bmr和blt的启动子相互作用，并诱导这些基因的转录。此外，该结构域还刺激mta基因本身以及至少另一个基因ydfK的表达，ydfK编码一种假定的膜蛋白。这些结果以及Mta与天蓝色链霉菌的硫链丝菌素诱导蛋白TipA的相似性，强烈表明Mta是一种自身调控型的全局转录调节因子，其活性受一种尚未确定的诱导剂刺激。去除C端诱导剂结合结构域可模拟这种刺激。Bmr和Blt都受该调节因子控制，这一事实表明它们的某些功能要么相同，要么至少相关。对Mta介导的调控进行进一步分析，可能会揭示枯草芽孢杆菌中多药转运蛋白系统的天然功能，并为其他细菌中的类似系统提供范例。
