Mycobacterium tuberculosisEspB binds phospholipids and mediates EsxA-independent virulence
Mycobacterium tuberculosisEspB binds phospholipids and mediates EsxA-independent virulence
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DOI：
10.1111/mmi.12336
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发表时间：
2013-09-01
影响因子：
3.6
通讯作者：
Cole, Stewart T.
中科院分区：
文献类型：
--
作者：
Chen, Jeffrey M.;Zhang, Ming;Cole, Stewart T.
由esx-1基因座编码的VII型ESX-1分泌装置对于结核分枝杆菌的两种主要毒力因子EsxA和EsxB的输出是必需的。ESX-1还需要未连接的espACD操纵子的产物以实现最佳功能，并且这些蛋白质被认为是分泌装置的组成部分。在这里，我们表明espACD操纵子不是必需的EspB，另一个ESX-1底物的分泌，这种不受阻碍的分泌EspB与显着的残留毒力。在进一步的研究中，我们发现纯化的EspB可以促进结核分枝杆菌的毒力，即使在EsxA和EsxB的情况下，并且可以通过结合生物活性磷脂磷脂酸和磷脂酰丝氨酸来实现，这两者都是在真核细胞信号传导中具有突出作用的有效生物活性分子。我们的研究结果为espACD操纵子对ESX-1装置的影响提供了新的见解，并揭示了EspB的独特毒力功能，在结核分枝杆菌-宿主相互作用中具有新的意义。
The type-VII ESX-1 secretion apparatus, encoded by the esx-1 genetic locus, is essential for the export of EsxA and EsxB, two major virulence factors of Mycobacterium tuberculosis. ESX-1 also requires the products of the unlinked espACD operon for optimal function and these proteins are considered integral parts of the secretion apparatus. Here we show that the espACD operon is not necessary for the secretion of EspB, another ESX-1 substrate, and this unimpeded secretion of EspB is associated with significant residual virulence. Upon further investigation, we found that purified EspB can facilitate M.tb virulence even in the absence of EsxA and EsxB, and may do so by binding the bioactive phospholipids phosphatidic acid and phosphatidylserine, both of which are potent bioactive molecules with prominent roles in eukaryotic cell signalling. Our findings provide new insights into the impact of the espACD operon on the ESX-1 apparatus and reveal a distinct virulence function for EspB with novel implications in M.tb-host interactions.