The Pseudomonas aeruginosa Type VI Secretion PGAP1-like Effector Induces Host Autophagy by Activating Endoplasmic Reticulum Stress
The Pseudomonas aeruginosa Type VI Secretion PGAP1-like Effector Induces Host Autophagy by Activating Endoplasmic Reticulum Stress
复制标题
铜绿假单胞菌 VI 型分泌 PGAP1 样效应子通过激活内质网应激诱导宿主自噬
DOI：
10.1016/j.celrep.2016.07.012
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发表时间：
2016-08-09
期刊：
影响因子：
8.8
通讯作者：
Jin, Qi
中科院分区：
文献类型：
--
作者：
Jiang, Feng;Wang, Xia;Jin, Qi
铜绿假单胞菌是一种机会致病菌，经常引起住院患者院内感染。VI型分泌系统（T6SS）负责分泌许多毒力效应蛋白，这些蛋白既可以干扰竞争微生物，也可以操纵宿主细胞。在这里，我们报告了铜绿假单胞菌h2 - t6ss依赖性磷脂酶效应，TpIE，作为跨王国毒素的详细调查。将TpIE传递到竞争细菌的质周空间导致生长抑制。重要的是，TpIE还含有真核pgap1样结构域，其靶向宿主内质网装置，最终导致内质网的破坏。TpIE活性通过IRE1 α - xbp1途径激活未折叠蛋白反应（UPR），增强自噬通量。这些发现表明，这种T6SS传递的磷脂酶效应物对原核和真核细胞靶标都有活性，突出了T6SS作为假单胞菌武器库中的多功能武器。
Pseudomonas aeruginosa is an opportunistic pathogen that regularly causes nosocomial infections in hospitalized patients. The type VI secretion system (T6SS) is responsible for the secretion of numerous virulence effector proteins that can both interfere with competing microbes and manipulate host cells. Here, we report a detailed investigation of a P. aeruginosa H2-T6SS-dependent phospholipase effector, TpIE, which acts as a trans-kingdom toxin. Delivery of TpIE to the periplasmic space of rival bacteria leads to growth inhibition. Importantly, TpIE, also contains a eukaryotic PGAP1-like domain, which targets the host ER apparatus, ultimately leading to disruption of the ER. TpIE activity leads to the activation of the unfolded protein response (UPR) through the IRE1 alpha-XBP1 pathway, enhancing autophagic flux. These findings indicate that this T6SS-delivered phospholipase effector is active against both prokaryotic and eukaryotic cellular targets, highlighting the T6SS as a versatile weapon in the Pseudomonas arsenal.