Intricate Genetic Programs Controlling Dormancy in Mycobacterium tuberculosis.
Intricate Genetic Programs Controlling Dormancy in Mycobacterium tuberculosis.
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DOI：
10.1016/j.celrep.2020.107577
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发表时间：
2020-04-28
期刊：
影响因子：
8.8
通讯作者：
Baliga NS
中科院分区：
文献类型：
--
作者：
Peterson EJR;Abidi AA;Arrieta-Ortiz ML;Aguilar B;Yurkovich JT;Kaur A;Pan M;Srinivas V;Shmulevich I;Baliga NS
结核分枝杆菌 (MTB) 显示出进入和退出休眠状态的非凡能力，这是病原体逃避免疫系统和利用易感个体的能力的标志。揭示 MTB 在疾病潜伏期和再激活期间表型变化背后的基因调控程序是一个挑战。我们开发了一个实验系统来精确控制 MTB 培养物中的溶解氧水平，以便捕获 MTB 进入和退出缺氧诱导的休眠状态时发生的转录事件。利用全面的全基因组转录因子结合图谱和网络拓扑分析的见解，我们确定了能够确定性地驱动六种转录和功能不同状态（涵盖超过五分之三的 MTB 基因组）的顺序转换的调节电路。遗传程序的结构解释了细胞同步进入休眠状态的转录动力学，该状态准备在遇到有利条件时感染宿主。结核分枝杆菌 (MTB) 通过对抗包括缺氧在内的不同应激源而在宿主体内持续存在。彼得森等人。报告了一个转录程序，该程序协调顺序状态转换以驱动 MTB 进出缺氧诱导的休眠状态。在各种特性中，该程序编码了在有利条件下感染宿主的高级准备。
Mycobacterium tuberculosis (MTB) displays the remarkable ability to transition in and out of dormancy, a hallmark of the pathogen’s capacity to evade the immune system and exploit susceptible individuals. Uncovering the gene regulatory programs that underlie the phenotypic shifts in MTB during disease latency and reactivation has posed a challenge. We develop an experimental system to precisely control dissolved oxygen levels in MTB cultures in order to capture the transcriptional events that unfold as MTB transitions into and out of hypoxia-induced dormancy. Using a comprehensive genome-wide transcription factor binding map and insights from network topology analysis, we identify regulatory circuits that deterministically drive sequential transitions across six transcriptionally and functionally distinct states encompassing more than three-fifths of the MTB genome. The architecture of the genetic programs explains the transcriptional dynamics underlying synchronous entry of cells into a dormant state that is primed to infect the host upon encountering favorable conditions. Mycobacterium tuberculosis (MTB) persists within the host by counteracting disparate stressors including hypoxia. Peterson et al. report a transcriptional program that coordinates sequential state transitions to drive MTB in and out of hypoxia-induced dormancy. Among varied properties, this program encodes advanced preparedness to infect the host in favorable conditions.
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