Polar localization of virulence-related Esx-1 secretion in mycobacteria.
Polar localization of virulence-related Esx-1 secretion in mycobacteria.
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DOI：
10.1371/journal.ppat.1000285
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发表时间：
2009-01
期刊：
影响因子：
6.7
通讯作者：
Brown, Eric J.
中科院分区：
文献类型：
--
作者：
Carlsson, Fredric;Joshi, Shilpa A.;Rangell, Linda;Brown, Eric J.
Esx-1（VII型）分泌系统对结核分枝杆菌和海洋分枝杆菌的毒力都至关重要，并且在两个物种之间高度保守。尽管它的重要性，但到目前为止还没有直接可视化的Esx-1分泌。In M. marinum，我们发现Mh 3864，一种新的Esx-1底物，仍然部分细胞壁相关易位后，发生在极地地区，表明Esx-1分泌发生在这些地区。感染的宿主细胞中Esx-1分泌的分析表明Esx-1活性在体内类似地定位。Esx-1装置的核心组分Mh 3870也定位于细菌极，显示出对具有活性细胞壁肽聚糖（PGN）合成的新极的偏好。这项工作表明，Esx-1分泌机器定位于细菌极点，并在细菌极点活跃。因此，毒力相关的蛋白质分泌定位于分枝杆菌，提示新的潜在的治疗靶点，这是迫切需要的。分枝杆菌代表了全球主要的人类健康问题，并且迫切需要鉴定新的过程和机制，包括治疗靶点。Esx-1分泌系统是结核分枝杆菌和海分枝杆菌引起疾病所必需的，并且在疫苗菌株如牛分枝杆菌BCG中不存在。Esx-1在M.结核和实验上可行的M. marinum，它越来越多地用于研究这种分泌系统。细菌细胞在空间上是高度组织化的;特别地，致病细菌可以将毒力相关的蛋白质分泌定位于细胞包膜内的特定区域，这是通常认为对毒力重要的特征。然而，目前还不知道Esx-1是否被划分。我们的工作代表了分枝杆菌蛋白质分泌的第一次可视化。具体来说，我们表明，Esx-1装置定位于，并在细菌极活跃在M。marinum。这些发现提示了以前未被认识的分枝杆菌蛋白质分泌定位的机制，可能包括新的治疗靶点。
The Esx-1 (type VII) secretion system is critical for virulence of both Mycobacterium tuberculosis and Mycobacterium marinum, and is highly conserved between the two species. Despite its importance, there has been no direct visualization of Esx-1 secretion until now. In M. marinum, we show that secretion of Mh3864, a novel Esx-1 substrate that remains partially cell wall–associated after translocation, occurred in polar regions, indicating that Esx-1 secretion takes place in these regions. Analysis of Esx-1 secretion in infected host cells suggested that Esx-1 activity is similarly localized in vivo. A core component of the Esx-1 apparatus, Mh3870, also localized to bacterial poles, showing a preference for new poles with active cell wall peptidoglycan (PGN) synthesis. This work demonstrates that the Esx-1 secretion machine localizes to, and is active at, the bacterial poles. Thus, virulence-related protein secretion is localized in mycobacteria, suggesting new potential therapeutic targets, which are urgently needed. Mycobacteria represent a major human health problem globally, and there is a pressing need to identify novel processes and mechanisms including therapeutic targets. The Esx-1 secretion system is required for both Mycobacterium tuberculosis and Mycobacterium marinum to cause disease, and is absent from vaccine strains such as Mycobacterium bovis BCG. Esx-1 is functionally conserved between M. tuberculosis and the experimentally amenable M. marinum, which is increasingly used to study this secretory system. Bacterial cells are spatially highly organized; in particular, pathogenic bacteria may localize virulence-related protein secretion to specific regions within the cell envelope, a feature that is generally believed to be important for virulence. However, it has not been known whether Esx-1 is compartmentalized. Our work represents the first visualization of protein secretion in mycobacteria in general. Specifically, we show that the Esx-1 apparatus localizes to, and is active at, the bacterial poles in M. marinum. These findings suggest previously unappreciated mechanisms governing localization of protein secretion in mycobacteria, potentially including new therapeutic targets.
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影响因子：
3.4
作者：
Koo, Ingrid C.;Wang, Chen;Brown, Eric J.
通讯作者：
Brown, Eric J.
影响因子：
3.1
作者：
RATLIFF, TL;MCCARTHY, R;BROWN, EJ
通讯作者：
BROWN, EJ
影响因子：
6.7
作者：
McLaughlin B;Chon JS;MacGurn JA;Carlsson F;Cheng TL;Cox JS;Brown EJ
通讯作者：
Brown EJ
DOI：
10.1073/pnas.0504922102
发表时间：
2005-07-26
影响因子：
11.1
作者：
Fortune, SM;Jaeger, A;Rubin, EJ
通讯作者：
Rubin, EJ
影响因子：
3.6
作者：
Gao, LY;Guo, S;Brown, EJ
通讯作者：
Brown, EJ