Mycobacterial WhiB6 Differentially Regulates ESX-1 and the Dos Regulon to Modulate Granuloma Formation and Virulence in Zebrafish
Mycobacterial WhiB6 Differentially Regulates ESX-1 and the Dos Regulon to Modulate Granuloma Formation and Virulence in Zebrafish
复制标题
分枝杆菌 WhiB6 差异调节 ESX-1 和 Dos 调节子以调节斑马鱼肉芽肿形成和毒力
DOI：
10.1016/j.celrep.2016.07.080
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发表时间：
2016-08-30
期刊：
影响因子：
8.8
通讯作者：
Chen, Shiyun
中科院分区：
文献类型：
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作者：
Chen, Zhenkang;Hu, Yangbo;Chen, Shiyun
在感染过程中，结核分枝杆菌（Mtb）暴露于多种氧化还原应激，引发代谢和生理变化。这些压力如何被感知并传递到Mtb转录装置仍不清楚。在这里，我们提供的证据表明，WhiB 6通过其Fe-S簇差异调节ESX-1和DosR调节子。当用NO激发时，WhiB 6持续激活DosR调节子的表达，但通过初始激活随后逐渐抑制来调节ESX-1表达。比较转录组学分析的全息和减少apo-WhiB 6补充菌株证实了这些结果，也揭示了WhiB 6控制有氧和无氧代谢，细胞分裂，和毒力。使用海洋分枝杆菌斑马鱼感染模型，我们发现，全息和apo-WhiB 6调节水平的分枝杆菌感染，肉芽肿形成和传播。这些发现为WhiB 6在分枝杆菌感染、传播和疾病发展中的作用提供了新的见解。
During the course of infection, Mycobacterium tuberculosis (Mtb) is exposed to diverse redox stresses that trigger metabolic and physiological changes. How these stressors are sensed and relayed to the Mtb transcriptional apparatus remains unclear. Here, we provide evidence that WhiB6 differentially regulates the ESX-1 and DosR regulons through its Fe-S cluster. When challenged with NO, WhiB6 continually activates expression of the DosR regulons but regulates ESX-1 expression through initial activation followed by gradual inhibition. Comparative transcriptomic analysis of the holo-and reduced apo-WhiB6 complemented strains confirms these results and also reveals that WhiB6 controls aerobic and anaerobic metabolism, cell division, and virulence. Using the Mycobacterium marinum zebrafish infection model, we find that holo-and apo-WhiB6 modulate levels of mycobacterial infection, granuloma formation, and dissemination. These findings provide fresh insight into the role of WhiB6 in mycobacterial infection, dissemination, and disease development.