Energy Bioscience Institute, University of California, Berkeley, California 94720, USA.
J Bacteriol. 2011 Jul;193(14):3446-52. doi: 10.1128/JB.00179-11. Epub 2011 May 20.
In response to stresses, Mycobacterium cells become dormant. This process is regulated by the DosR transcription factor. In Mycobacterium tuberculosis, the dormancy regulon is well characterized and contains the dosR gene itself and dosS and dosT genes encoding DosR kinases, nitroreductases (acg; Rv3131), diacylglycerol acyltransferase (DGAT) (Rv3130c), and many universal stress proteins (USPs). In this study, we apply comparative genomic analysis to characterize the DosR regulons in nine Mycobacterium genomes, Rhodococcus sp. RHA1, Nocardia farcinica, and Saccharopolyspora erythraea. The regulons are highly labile, containing eight core gene groups (regulators, kinases, USPs, DGATs, nitroreductases, ferredoxins, heat shock proteins, and the orthologs of the predicted kinase [Rv2004c] from M. tuberculosis) and 10 additional genes with more restricted taxonomic distribution that are mostly involved in anaerobic respiration. The largest regulon is observed in M. marinum and the smallest in M. abscessus. Analysis of large gene families encoding USPs, nitroreductases, and DGATs demonstrates a mosaic distribution of regulated and nonregulated members, suggesting frequent acquisition and loss of DosR-binding sites.
在应激反应下，分枝杆菌细胞进入休眠状态。这一过程受 DosR 转录因子调控。在结核分枝杆菌中，休眠调控基因已得到充分研究，包含 dosR 基因及其编码 DosR 激酶、硝基还原酶（acg；Rv3131）、二酰基甘油酰基转移酶（DGAT）（Rv3130c）和许多普遍应激蛋白（USP）的 dosS 和 dosT 基因。在这项研究中，我们应用比较基因组分析来描述 9 种分枝杆菌基因组、红球菌 RHA1、诺卡氏菌 farcinica 和绛红小单孢菌中的 DosR 调控基因群。这些调控基因群高度不稳定，包含 8 个核心基因群（调控因子、激酶、USP、DGAT、硝基还原酶、铁氧还蛋白、热休克蛋白和结核分枝杆菌预测激酶 [Rv2004c] 的同源物）和 10 个具有更严格分类分布的额外基因，这些基因主要参与厌氧呼吸。在海洋分枝杆菌中观察到最大的调控基因群，而在脓肿分枝杆菌中观察到最小的调控基因群。对编码 USP、硝基还原酶和 DGAT 的大型基因家族的分析表明，受调控和非调控成员的分布呈镶嵌状，表明 DosR 结合位点经常发生获得和丢失。
