Vibrio VopQ induces PI3-kinase-independent autophagy and antagonizes phagocytosis.

Vibrio VopQ induces PI3-kinase-independent autophagy and antagonizes phagocytosis.
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DOI:
10.1111/j.1365-2958.2009.06798.x
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发表时间:
2009-08
影响因子:
3.6
通讯作者:
Orth K
Orth K
中科院分区:
生物学2区
文献类型:
--
作者:
Burdette DL;Seemann J;Orth K

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副溶血性弧菌(V. para)是一种革兰氏阴性菌,可因食用受污染的贝类而引起胃肠炎。这种细菌拥有两个III型分泌系统,每个染色体上一个。1号染色体上的III型分泌系统通过一系列暂时受控的事件诱导细胞死亡,这些事件不依赖于caspase,首先包括诱导自噬,然后是细胞围合,最后是细胞裂解。VopQ是诱导自噬所必需的III型分泌效应物,因为缺乏VopQ的突变株在感染期间诱导自噬的能力减弱。通过将重组VopQ微量注射到GFP-LC3 HeLa细胞中,可以证明VopQ足以诱导快速自噬。我们的研究结果表明,VopQ是V. para介导的细胞死亡过程中诱导自噬的必要条件和充分条件,这种作用不依赖于磷脂酰肌醇-3激酶,但需要Atg5。此外,诱导vopq介导的自噬阻止了V. para在感染期间吞噬所需的必要细胞机制的募集。这些数据为V. para致病的机制提供了重要的见解。
Vibrio parahaemolyticus (V. para) is a Gram-negative bacterium responsible for gastroenteritis acquired from the consumption of contaminated shellfish. This bacterium harbors two type III secretion systems, one on each chromosome. The type III secretion system on chromosome I induces cell death by a temporally controlled sequence of events that is caspase independent and first involves induction of autophagy, followed by cellular rounding, and finally cellular lysis. VopQ is a type III secreted effector that is necessary for the induction of autophagy as mutant strains lacking VopQ are attenuated in their ability to induce autophagy during infection. VopQ is sufficient to induce rapid autophagy as demonstrated by microinjection of recombinant VopQ into GFP-LC3 HeLa cells. Our results demonstrate that VopQ is both necessary and sufficient for induction of autophagy during V. para-mediated cell death and this effect is independent of phosphatidylinositol-3-kinases but requires Atg5. Furthermore, induction of VopQ-mediated autophagy prevents recruitment of the necessary cellular machinery required for phagocytosis of V. para during infection. These data provide important insights into the mechanism used by V. para to cause disease.
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