CsoR Is Essential for Maintaining Copper Homeostasis in Mycobacterium tuberculosis.
CsoR Is Essential for Maintaining Copper Homeostasis in Mycobacterium tuberculosis.
复制标题
DOI：
10.1371/journal.pone.0151816
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Talaat AM
中科院分区：
文献类型：
--
作者：
Marcus SA;Sidiropoulos SW;Steinberg H;Talaat AM
结核分枝杆菌是感染世界三分之一人口的病原体，在宿主体内面临许多挑战，包括高水平的铜。我们以前已经证明，M。结核病CsoR是铜诱导的转录调节因子。在这里，我们研究的假设，csoR是必要的维持铜稳态和生存在各种压力条件下。利用未标记的csoR敲除菌株，我们能够表征csoR在M.结核病，因为它面临铜和宿主的压力。在高铜水平下的生长表明，M。在没有csoR的情况下，结核病患者在铜应激下明显更好地存活。然而，在最低水平的铜，差异表达分析表明，在细胞范围内的缺氧型应激反应与诱导的DosR调节子的csoR的损失的结果。尽管对M施加了压力。在小鼠感染的早期慢性阶段，与野生型相比，敲除菌株的存活增加，表明csoR可以在调节M.结核病在宿主体内的适应性。总体而言，对CsoR的分析增加了对M.结核病铜反应与其他细胞内病原体窝藏CsoR的影响。
Mycobacterium tuberculosis, a pathogen infecting one third of the world population, faces numerous challenges within the host, including high levels of copper. We have previously shown that M. tuberculosis CsoR is a copper inducible transcriptional regulator. Here we examined the hypothesis that csoR is necessary for maintaining copper homeostasis and surviving under various stress conditions. With an unmarked csoR knockout strain, we were able to characterize the role of csoR in M. tuberculosis as it faced copper and host stress. Growth under high levels of copper demonstrated that M. tuberculosis survives copper stress significantly better in the absence of csoR. Yet under minimal levels of copper, differential expression analysis revealed that the loss of csoR results in a cell wide hypoxia-type stress response with the induction of the DosR regulon. Despite the stress placed on M. tuberculosis by the loss of csoR, survival of the knockout strain was increased compared to wild type during the early chronic stages of mouse infection, suggesting that csoR could play an active role in modulating M. tuberculosis fitness within the host. Overall, analysis of CsoR provided an increased understanding of the M. tuberculosis copper response with implications for other intracellular pathogens harboring CsoR.