Components of the Rv0081-Rv0088 Locus, Which Encodes a Predicted Formate Hydrogenlyase Complex, Are Coregulated by Rv0081, MprA, and DosR in Mycobacterium tuberculosis
Components of the Rv0081-Rv0088 Locus, Which Encodes a Predicted Formate Hydrogenlyase Complex, Are Coregulated by Rv0081, MprA, and DosR in Mycobacterium tuberculosis
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DOI：
10.1128/jb.05562-11
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发表时间：
2011-10-01
影响因子：
3.2
通讯作者：
Zahrt, Thomas C.
中科院分区：
文献类型：
--
作者：
He, Hongjun;Bretl, Daniel J.;Zahrt, Thomas C.
结核分枝杆菌是结核病的病原体，尽管有疫苗和具有成本效益的抗生素，但它仍然是全世界发病和死亡的重要原因。这种微生物的成功可部分归因于其适应宿主内潜在有害应激的能力，以及在肉芽肿结构内建立、维持和从长期持续感染中重新激活的能力。DosRS-DosT/DevRS-Rv 2027 c和MprAB双组分信号转导系统先前已涉及M.结核病，并且已知对可能在肉芽肿内发现的病症有反应。在这里，我们描述了一个基因座（Rv 0081-Rv 0088）的编码预测的甲酸氢酶复合物，直接由DosR/DevR和MprA，和在这个操纵子，Rv 0081中的第一个基因的产物的组件的初始表征。特别是，我们证明，Rv 0081负调控其自身的表达和下游基因的结合在其上游区域的反向重复元件。相反，DosR/DevR和MprA分别通过结合与Rv 0081识别的识别序列部分或完全重叠的识别序列来正向调节Rv 0081的表达。Rv 0081的表达起始于两个启动子元件;一个启动子位于DosR/DevR结合位点的下游，但与Rv 0081和MprA识别的序列重叠，另一个启动子位于DosR/DevR、Rv 0081和MprA结合位点的下游。有趣的是，Rv 0081抑制Rv 0081和下游决定簇后，激活DosRS-DosT/DevRS-Rv 2027 c的一氧化氮，这表明该基因座的表达是复杂的，并受到多个层次的调控。基于这一点和其他已发表的信息，提出了一个模型，详细说明Rv 0081-Rv 0088的表达，这些转录因子在特定的生长环境。
Mycobacterium tuberculosis, the etiological agent of tuberculosis, remains a significant cause of morbidity and mortality throughout the world despite a vaccine and cost-effective antibiotics. The success of this organism can be attributed, in part, to its ability to adapt to potentially harmful stress within the host and establish, maintain, and reactivate from long-term persistent infection within granulomatous structures. The DosRS-DosT/DevRS-Rv2027c, and MprAB two-component signal transduction systems have previously been implicated in aspects of persistent infection by M. tuberculosis and are known to be responsive to conditions likely to be found within the granuloma. Here, we describe initial characterization of a locus (Rv0081-Rv0088) encoding components of a predicted formate hydrogenylase enzyme complex that is directly regulated by DosR/DevR and MprA, and the product of the first gene in this operon, Rv0081. In particular, we demonstrate that Rv0081 negatively regulates its own expression and that of downstream genes by binding an inverted repeat element in its upstream region. In contrast, DosR/DevR and MprA positively regulate Rv0081 expression by binding to recognition sequences that either partially or completely overlap that recognized by Rv0081, respectively. Expression of Rv0081 initiates from two promoter elements; one promoter located downstream of the DosR/DevR binding site but overlapping the sequence recognized by both Rv0081 and MprA and another promoter downstream of the DosR/DevR, Rv0081, and MprA binding sites. Interestingly, Rv0081 represses Rv0081 and downstream determinants following activation of DosRS-DosT/DevRS-Rv2027c by nitric oxide, suggesting that expression of this locus is complex and subject to multiple levels of regulation. Based on this and other published information, a model is proposed detailing Rv0081-Rv0088 expression by these transcription factors within particular growth environments.