Honaker Ryan W, Leistikow Rachel L, Bartek Iona L, Voskuil Martin I
University of Colorado Denver, Department of Microbiology, Aurora, CO 80045, USA.
Infect Immun. 2009 Aug;77(8):3258-63. doi: 10.1128/IAI.01449-08. Epub 2009 Jun 1.
In Mycobacterium tuberculosis, the sensor kinases DosT and DosS activate the transcriptional regulator DosR, resulting in the induction of the DosR regulon, which is important for anaerobic survival and perhaps latent infection. The individual and collective roles of these sensors have been postulated biochemically, but their roles in vivo have remained unclear. This work demonstrates distinct and additive roles for each sensor during anaerobic dormancy. Both sensors are necessary for wild-type levels of DosR regulon induction, and concomitantly, full induction of the regulon is required for wild-type anaerobic survival. In the anaerobic model, DosT plays an early role, responding to hypoxia. DosT then induces the regulon and with it DosS, which sustains and further induces the regulon. DosT then loses its functionality as oxygen becomes limited, and DosS alone maintains induction of the genes from that point forward. Thus, M. tuberculosis has evolved a system whereby it responds to hypoxic conditions in a stepwise fashion as it enters an anaerobic state.
在结核分枝杆菌中，传感激酶DosT和DosS激活转录调节因子DosR，从而诱导DosR调控子的表达，这对于厌氧生存以及可能的潜伏感染至关重要。这些传感器各自以及共同发挥的作用已通过生化方法进行了推测，但它们在体内的作用仍不明确。这项研究表明，在厌氧休眠期间，每个传感器都发挥着独特且互补的作用。野生型水平的DosR调控子诱导需要这两种传感器，同时，野生型厌氧生存需要调控子的完全诱导。在厌氧模型中，DosT发挥早期作用，对缺氧作出反应。然后DosT诱导调控子以及DosS，DosS维持并进一步诱导调控子。随着氧气变得有限，DosT随后失去其功能，从那时起仅由DosS维持基因的诱导。因此，结核分枝杆菌已经进化出一种系统，使其在进入厌氧状态时以逐步的方式对缺氧条件作出反应。
