Ma D, Alberti M, Lynch C, Nikaido H, Hearst J E
Department of Chemistry, University of California, Berkeley 94720, USA.
Mol Microbiol. 1996 Jan;19(1):101-12. doi: 10.1046/j.1365-2958.1996.357881.x.
Genes acrAB encode a multidrug efflux pump in Escherichia coli. We have previously reported that transcription of acrAB is increased under general stress conditions (i.e. 4% ethanol, 0.5 M NaCl, and the stationary phase in Luria-Bertani medium). In this study, lacZ transcriptional fusions and an in vitro gel mobility shift assay have been utilized to study the mechanisms governing the regulation of acrAB. We found that a closely linked gene, acrR, encoded a repressor of acrAB. Nevertheless, the general stress conditions increased transcription of acrAB in the absence of functional AcrR, and such conditions surprisingly increased the transcription of acrR even more strongly than that of acrAB. These results suggest that the general-stress-induced transcription of acrAB is primarily mediated by global regulatory pathway(s), and that one major role of AcrR is to function as a specific secondary modulator to fine tune the level of acrAB transcription and to prevent the unwanted overexpression of acrAB. To our knowledge, this represents a novel mechanism of regulating gene expression in E. coli. Evidence also suggests that the up-regulation of acrAB expression under general stress conditions is not likely to be mediated by the known global regulators, such as MarA or SoxS, although elevated levels of these proteins were shown to increase the transcription of acrAB.
基因acrAB在大肠杆菌中编码一种多药外排泵。我们之前报道过，在一般应激条件下（即4%乙醇、0.5M氯化钠以及在Luria-Bertani培养基中的稳定期），acrAB的转录会增加。在本研究中，利用lacZ转录融合和体外凝胶迁移率变动分析来研究调控acrAB的机制。我们发现一个紧密连锁的基因acrR编码acrAB的阻遏物。然而，在没有功能性AcrR的情况下，一般应激条件会增加acrAB的转录，而且令人惊讶的是，这些条件下acrR的转录增加得甚至比acrAB还要强烈。这些结果表明，一般应激诱导的acrAB转录主要由全局调控途径介导，并且AcrR的一个主要作用是作为一种特定的二级调节因子，微调acrAB转录水平并防止acrAB不必要的过度表达。据我们所知，这代表了大肠杆菌中一种新的基因表达调控机制。有证据还表明，尽管已知这些蛋白质水平升高会增加acrAB的转录，但一般应激条件下acrAB表达的上调不太可能由已知的全局调控因子（如MarA或SoxS）介导。
