Mycobacterium tuberculosis septum site determining protein, Ssd encoded by rv3660c, promotes filamentation and elicits an alternative metabolic and dormancy stress response.
Mycobacterium tuberculosis septum site determining protein, Ssd encoded by rv3660c, promotes filamentation and elicits an alternative metabolic and dormancy stress response.
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DOI：
10.1186/1471-2180-11-79
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发表时间：
2011-04-19
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：
England K;Crew R;Slayden RA
在结核分枝杆菌中，参与细胞分裂和细胞周期进程调控的蛋白质仍不明确。此外，越来越多的人认识到，在分裂点调节细胞复制对于建立非复制持续状态是重要的。因此，本研究的目的是使用由共识建模生物信息学、超微结构分析和转录图谱组成的系统方法来鉴定参与M适应性代谢反应的隔膜调节蛋白。结核通过生物信息学分析，发现rv3660c编码的隔膜位点决定蛋白（Ssd）是放线菌中隔膜位点调节蛋白的直向同源物。ssd在M.耻垢分枝杆菌和M.结核病抑制隔膜形成，导致细长的细胞缺乏隔膜。M.结核显示增加的SSD表达引起独特的反应，包括休眠调节子和被认为在适应性代谢中起作用的替代性σ因子。通过转座子插入破坏rv3660c否定了独特的转录反应，并导致细菌长度减少。这项研究建立了第一个连接之间的隔膜调节蛋白和诱导的替代代谢组成的替代西格玛因素和休眠调节子，这是与建立一个非复制持久的细胞内生活方式。参与细胞周期调控的休眠反应，无论是直接或间接的监管组件的识别，提供了一个基础，为进一步的研究，并进一步了解复杂的机制，参与建立一个非复制状态和恢复增长。
Proteins that are involved in regulation of cell division and cell cycle progression remain undefined in Mycobacterium tuberculosis. In addition, there is a growing appreciation that regulation of cell replication at the point of division is important in establishing a non-replicating persistent state. Accordingly, the objective of this study was to use a systematic approach consisting of consensus-modeling bioinformatics, ultrastructural analysis, and transcriptional mapping to identify septum regulatory proteins that participate in adaptive metabolic responses in M. tuberculosis. Septum site determining protein (Ssd), encoded by rv3660c was discovered to be an ortholog of septum site regulating proteins in actinobacteria by bioinformatics analysis. Increased expression of ssd in M. smegmatis and M. tuberculosis inhibited septum formation resulting in elongated cells devoid of septa. Transcriptional mapping in M. tuberculosis showed that increased ssd expression elicited a unique response including the dormancy regulon and alternative sigma factors that are thought to play a role in adaptive metabolism. Disruption of rv3660c by transposon insertion negated the unique transcriptional response and led to a reduced bacterial length. This study establishes the first connection between a septum regulatory protein and induction of alternative metabolism consisting of alternative sigma factors and the dormancy regulon that is associated with establishing a non-replicating persistent intracellular lifestyle. The identification of a regulatory component involved in cell cycle regulation linked to the dormancy response, whether directly or indirectly, provides a foundation for additional studies and furthers our understanding of the complex mechanisms involved in establishing a non-replicating state and resumption of growth.
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鉴定针对休眠期分枝杆菌感染的基因靶标。
影响因子：
3.7
作者：
Murphy DJ;Brown JR
通讯作者：
Brown JR
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影响因子：
15.8
作者：
Connolly, Lynn E.;Edelstein, Paul H.;Ramakrishnan, Lalita
通讯作者：
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影响因子：
5.2
作者：
Slayden, Richard A.;Belisle, John T.
通讯作者：
Belisle, John T.
DOI：
10.1073/pnas.95.6.2885
发表时间：
1998-03-17
影响因子：
11.1
作者：
Mukherjee, A;Cao, CN;Lutkenhaus, J
通讯作者：
Lutkenhaus, J
影响因子：
3.2
作者：
Lee, Jong-Hee;Geiman, Deborah E.;Bishai, William R.
通讯作者：
Bishai, William R.