Ahmed M, Lyass L, Markham P N, Taylor S S, Vázquez-Laslop N, Neyfakh A A
Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago 60612, USA.
J Bacteriol. 1995 Jul;177(14):3904-10. doi: 10.1128/jb.177.14.3904-3910.1995.
The Bacillus subtilis genome encodes two multidrug efflux transporters sharing 51% sequence identity: Bmr, described previously, and Blt, described here. Overexpression of either transporter in B. subtilis leads to a similar increase in resistance to ethidium bromide, rhodamine and acridine dyes, tetraphenylphosphonium, doxorubicin, and fluoroquinolone antibiotics. However, Blt differs widely from Bmr in its expression pattern. Under standard cultivation conditions, B. subtilis expresses Bmr but Blt expression is undetectable. We have previously shown that Bmr expression is regulated by BmrR, a member of the family of MerR-like transcriptional activators. Here we show that blt transcription is regulated by another member of the same family, BltR. The DNA-binding domains of BmrR and BltR are related, but their putative inducer-binding domains are dissimilar, suggesting that Bmr and Blt are expressed in response to different inducers. Indeed, rhodamine, a substrate of Bmr and Blt and a known inducer of Bmr expression, does not induce Blt expression. Blt expression has been observed only in B. subtilis, carrying mutation acfA, which, as we show here, alters the sequence of the blt gene promoter. Unlike bmr, which is transcribed as a monocistronic mRNA, blt is cotranscribed with a downstream gene encoding a putative acetyltransferase. Overall, the differences in transcriptional control and operon organization between bmr and blt suggest that the transporters encoded by these genes have independent functions involving the transport of distinct physiological compounds.
枯草芽孢杆菌基因组编码两种序列同一性为51%的多药外排转运蛋白：之前描述过的Bmr和本文描述的Blt。在枯草芽孢杆菌中过表达任何一种转运蛋白都会导致对溴化乙锭、罗丹明和吖啶染料、四苯基鏻、阿霉素和氟喹诺酮类抗生素的抗性有类似增加。然而，Blt在其表达模式上与Bmr有很大不同。在标准培养条件下，枯草芽孢杆菌表达Bmr，但检测不到Blt的表达。我们之前已经表明，Bmr的表达受MerR样转录激活因子家族成员BmrR的调控。在这里我们表明，blt转录受同一家族的另一个成员BltR的调控。BmrR和BltR的DNA结合结构域相关，但它们假定的诱导物结合结构域不同，这表明Bmr和Blt是对不同诱导物作出反应而表达的。实际上，罗丹明是Bmr和Blt的底物，也是已知的Bmr表达诱导物，但它不会诱导Blt的表达。仅在携带acfA突变的枯草芽孢杆菌中观察到Blt的表达，正如我们在此所示，该突变改变了blt基因启动子的序列。与转录为单顺反子mRNA的bmr不同，blt与一个编码假定乙酰转移酶的下游基因共转录。总体而言，bmr和blt在转录控制和操纵子组织上的差异表明，这些基因编码的转运蛋白具有独立的功能，涉及不同生理化合物的转运。
