Mce3R, a TetR-type transcriptional repressor, controls the expression of a regulon involved in lipid metabolism in Mycobacterium tuberculosis
Mce3R, a TetR-type transcriptional repressor, controls the expression of a regulon involved in lipid metabolism in Mycobacterium tuberculosis
复制标题
DOI：
10.1099/mic.0.027086-0
复制
发表时间：
2009-07-01
期刊：
影响因子：
2.8
通讯作者：
Bigi, Fabiana
中科院分区：
文献类型：
--
作者：
de la Paz Santangelo, Maria;Klepp, Laura;Bigi, Fabiana
mce操纵子构成结核分枝杆菌基因组中的四个同源区域，每个区域具有8-13个ORF。尽管Mce蛋白家族的功能尚未明确，但其成员被认为是膜脂转运蛋白。基于功能实验，我们发现mce3位点的调节因子Mce3R负向调节Rv1933c-Rv1935c和Rv1936-Rv1941转录单位的表达。这些操纵子彼此相邻并且转录方式不同。大多数这些基因的预测功能与脂质代谢或氧化还原反应有关。对差异表达基因 5' UTR 序列的生物信息分析使我们能够定义假定的 Mce3R 基序。重要的是，Mce3R 基序分别在 mce3R-yrbE3A 和 Rv1935c-Rv1936 基因间区域中出现 6 次和 3 次。在足迹分析中，该基序两次出现在 mce3 操纵子的两个受 Mce3R 保护的区域内，因此表明该基序可能充当启动子中 Mce3R 调节因子的操纵位点。此外，在缺乏 Mce3R 的情况下检测到结核分枝杆菌脂质含量的变化。总而言之，这些结果表明 Mce3R 控制 mce3 操纵子中编码的推定转运系统和参与 Mce3 转运底物修饰的酶的表达。
The mce operons constitute four homologous regions in the Mycobacterium tuberculosis genome, each of which has 8-13 ORFs. Although the function of the Mce protein family has not been clearly established, its members are believed to be membrane lipid transporters. Based on functional experiments, we found that the regulator of the mce3 locus, Mce3R, negatively regulates the expression of the Rv1933c-Rv1935c and Rv1936-Rv1941 transcriptional units. These operons are adjacent to one another and divergently transcribed. The predicted functions of most of these genes are related to either lipid metabolism or redox reactions. Bioinformatic analysis of the 5' UTR sequences of the differentially expressed genes allowed us to define a putative Mce3R motif. Importantly, the Mce3R motif was present six and three times in the mce3R-yrbE3A and Rv1935c-Rv1936 intergenic regions, respectively. Two occurrences of this motif mapped within the two regions of the mce3 operon that were protected by Mce3R in a footprinting analysis, thus indicating that this motif is likely to serve as an operator site for the Mce3R regulator in the promoter. In addition, alterations in the lipid content of M. tuberculosis were detected in the absence of Mce3R. Taken together, these results suggest that Mce3R controls the expression of both the putative transport system encoded in the mce3 operon and the enzymes implicated in the modification of the Mce3-transported substrates.