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

被引:90
作者
Burdette, Dara L. [1 ]
Seemann, Joachim [2 ]
Orth, Kim [1 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA
[2] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA
关键词
MAMMALIAN AUTOPHAGY; ACTIN CYTOSKELETON; UNITED-STATES; CELL-DEATH; PARAHAEMOLYTICUS; EFFECTOR; OYSTERS; YEAST; INACTIVATION; ACTIVATION;
D O I
10.1111/j.1365-2958.2009.06798.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Vibrio parahaemolyticus is a Gram-negative bacterium responsible for gastroenteritis acquired from the consumption of contaminated shellfish. This bacterium harbours 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 micro-injection of recombinant VopQ into GFP-LC3 HeLa cells. Our results demonstrate that VopQ is both necessary and sufficient for induction of autophagy during V. parahaemolyticus-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. parahaemolyticus during infection. These data provide important insights into the mechanism used by V. parahaemolyticus to cause disease.
引用
收藏
页码:639 / 649
页数:11
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