Transcriptomic analysis identifies growth rate modulation as a component of the adaptation of mycobacteria to survival inside the macrophage
Transcriptomic analysis identifies growth rate modulation as a component of the adaptation of mycobacteria to survival inside the macrophage
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DOI：
10.1128/jb.01787-06
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发表时间：
2007-06-01
影响因子：
3.2
通讯作者：
McFadden, J. J.
中科院分区：
文献类型：
--
作者：
Beste, D. J. V.;Laing, E.;McFadden, J. J.
结核杆菌对宿主环境的适应可能涉及一组复杂的基因调控事件和响应环境信号的生理开关。为了解构结核分枝杆菌在体内的生理状态，我们使用恒化器模型来研究生物体在体内状态的一个方面，即缓慢生长。牛分枝杆菌BCG在高和低生长速率下在碳限制恒化器中培养，并进行转录组学分析以鉴定与缓慢生长相关的基因调控事件。结果表明，生长缓慢与休眠存活调节子的几个基因的表达诱导有关。在恒化器模型中BCG的转录谱与M.结核病在巨噬细胞中的生长，这意味着病原体对巨噬细胞环境的反应的重要组成部分是对碳限制条件下缓慢生长的反应。这表明适应低生长速率对M.结核病，也有价值的恒化器模型解构成分的体内状态，这一重要的病原体。
The adaptation of the tubercle bacillus to the host environment is likely to involve a complex set of gene regulatory events and physiological switches in response to environmental signals. In order to deconstruct the physiological state of Mycobacterium tuberculosis in vivo, we used a chemostat model to study a single aspect of the organism's in vivo state, slow growth. Mycobacterium bovis BCG was cultivated at high and low growth rates in a carbon-limited chemostat, and transcriptomic analysis was performed to identify the gene regulation events associated with slow growth. The results demonstrated that slow growth was associated with the induction of expression of several genes of the dormancy survival regulon. There was also a striking overlap between the transcriptomic profile of BCG in the chemostat model and the response of M. tuberculosis to growth in the macrophage, implying that a significant component of the response of the pathogen to the macrophage environment is the response to slow growth in carbon-limited conditions. This demonstrated the importance of adaptation to a low growth rate to the virulence strategy of M. tuberculosis and also the value of the chemostat model for deconstructing components of the in vivo state of this important pathogen.