MazF6 toxin of Mycobacterium tuberculosis demonstrates antitoxin specificity and is coupled to regulation of cell growth by a Soj-like protein.
MazF6 toxin of Mycobacterium tuberculosis demonstrates antitoxin specificity and is coupled to regulation of cell growth by a Soj-like protein.
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DOI：
10.1186/1471-2180-13-240
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发表时间：
2013-10-31
期刊：
影响因子：
4.2
通讯作者：
Slayden RA
中科院分区：
文献类型：
--
作者：
Ramirez MV;Dawson CC;Crew R;England K;Slayden RA
结核分枝杆菌（Mtb）用于建立非复制持久性（NRP）的分子程序知之甚少。为了研究调节进入NRP的机制，我们询问细胞周期调节如何与最终导致NRP的下游适应相关联。根据以前的报告和我们最近的研究，我们的理由，为了建立NRP，细胞在细胞周期中停止在隔膜形成的点耦合的监管机制。使用生物信息学共识模型，我们确定了一个替代的细胞周期调控元件，SojMtb编码的rv1708。SojMtb协调涉及隔膜形成点处的细胞周期控制的调节机制，并促进MazF6毒素的诱导。MazF6作为mRNA干扰酶发挥作用，导致抑菌作用，可通过与其同源抗毒素MazE6相互作用来预防。此外，MazEF 6独立于其他Maz家族毒素：抗毒素对发挥作用。值得注意的是，在感染后20、40和100天鉴定到的soj Mtb和mazEF6转录物的丰度增加，表明在慢性感染期间的适应中的作用。在这里，我们提出了一个耦合的监管系统，其中通过SojMtb的细胞周期调控与下游的适应，通过MazEF6 TA对的活动促进的第一个证据。
Molecular programs employed by Mycobacterium tuberculosis (Mtb) for the establishment of non-replicating persistence (NRP) are poorly understood. In order to investigate mechanisms regulating entry into NRP, we asked how cell cycle regulation is linked to downstream adaptations that ultimately result in NRP. Based on previous reports and our recent studies, we reason that, in order to establish NRP, cells are halted in the cell cycle at the point of septum formation by coupled regulatory mechanisms. Using bioinformatic consensus modeling, we identified an alternative cell cycle regulatory element, SojMtb encoded by rv1708. SojMtb coordinates a regulatory mechanism involving cell cycle control at the point of septum formation and elicits the induction of the MazF6 toxin. MazF6 functions as an mRNA interferase leading to bacteriostasis that can be prevented by interaction with its cognate antitoxin, MazE6. Further, MazEF6 acts independently of other Maz family toxin:antitoxin pairs. Notably, soj Mtb and mazEF6 transcripts where identified at 20, 40 and 100 days post-infection in increasing abundance indicating a role in adaption during chronic infection. Here we present the first evidence of a coupled regulatory system in which cell cycle regulation via SojMtb is linked to downstream adaptations that are facilitated through the activity of the MazEF6 TA pair.
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影响因子：
6.4
作者：
Keren I;Minami S;Rubin E;Lewis K
通讯作者：
Lewis K
DOI：
10.1074/mcp.m112.018846
发表时间：
2013-05
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Albrethsen J;Agner J;Piersma SR;Højrup P;Pham TV;Weldingh K;Jimenez CR;Andersen P;Rosenkrands I
通讯作者：
Rosenkrands I
影响因子：
3.3
作者：
Mine, Natacha;Guglielmini, Julien;Van Melderen, Laurence
通讯作者：
Van Melderen, Laurence
影响因子：
11.4
作者：
Leonard, TA;Butler, PJ;Löwe, J
通讯作者：
Löwe, J
影响因子：
3.5
作者：
Grossman, TH;Kawasaki, ES;Osburne, MS
通讯作者：
Osburne, MS