Polar Localization of Virulence-Related Esx-1 Secretion in Mycobacteria

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.

Esx-1（VII型）分泌系统（Esx-1 (type VII) secretion system）对结核分枝杆菌（Mycobacterium tuberculosis）和海分枝杆菌（Mycobacterium marinum）的致病性均至关重要，且在两菌种间高度保守。尽管该系统功能意义重大，但迄今为止尚未有针对Esx-1分泌过程的直接可视化研究。在海分枝杆菌中，我们观测到新型Esx-1底物Mh3864——该底物在转位后仍部分结合于细胞壁——其分泌发生于菌体两极区域，这表明Esx-1分泌正是在这些区域进行。对感染宿主细胞内的Esx-1分泌过程进行分析后发现，其活性在体内同样呈现两极定位。Esx-1分泌装置的核心组分Mh3870同样定位于细菌菌体两极，且偏好定位于存在活跃细胞壁肽聚糖（PGN）合成的新极。本研究证实，Esx-1分泌装置定位于细菌菌体两极并在此发挥活性。由此可见，分枝杆菌中与致病性相关的蛋白质分泌存在定位特异性，这为当前亟需开发的新型治疗靶点提供了潜在方向。