Two sensor kinases contribute to the hypoxic response of Mycobacterium tuberculosis
Two sensor kinases contribute to the hypoxic response of Mycobacterium tuberculosis
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DOI：
10.1074/jbc.m401230200
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发表时间：
2004-05-28
影响因子：
4.8
通讯作者：
Sherman, DR
中科院分区：
文献类型：
--
作者：
Roberts, DM;Liao, RLP;Sherman, DR
目前的估计表明，近三分之一的世界人口潜伏感染结核分枝杆菌。氧张力降低和一氧化氮暴露是杆菌在体内遇到的两种可能促进潜伏期的条件。体外暴露于缺氧或一氧化氮导致细菌停滞，伴随着由转录因子DosR控制的47基因调节子的诱导。在这份报告中，我们表明，dosS基因相邻的dosR和另一个基因，dosT（Rv 2027 c），编码传感器激酶，其中每一个可以在一个保守的组氨酸自磷酸化，然后转移磷酸到天冬氨酸残基的DosR。缺乏这两种传感器的突变细菌无法激活DosR调节基因的表达。这些数据表明，DosR/DoS/DoS T包含一个双组分信号系统，这是M.结核病对缺氧和一氧化氮的遗传反应，这两种条件在体外产生可逆的生长停滞，并可能导致体内潜伏期。
Current estimates indicate that nearly a third of the world's population is latently infected with Mycobacterium tuberculosis. Reduced oxygen tension and nitric oxide exposure are two conditions encountered by bacilli in vivo that may promote latency. In vitro exposure to hypoxia or nitric oxide results in bacterial stasis with concomitant induction of a 47-gene regulon controlled by the transcription factor DosR. In this report we demonstrate that both the dosS gene adjacent to dosR and another gene, dosT (Rv2027c), encode sensor kinases, each of which can autophosphorylate at a conserved histidine and then transfer phosphate to an aspartate residue of DosR. Mutant bacteria lacking both sensors are unable to activate expression of DosR-regulated genes. These data indicate that DosR/DosS/DosT comprise a two-component signaling system that is required for the M. tuberculosis genetic response to hypoxia and nitric oxide, two conditions that produce reversible growth arrest in vitro and may contribute to latency in vivo.