Vibrio VopQ induces PI3-kinase-independent autophagy and antagonizes phagocytosis.
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 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. 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.
Burdette
Dara L
DL
Department of Molecular Biology, University of Texas South-western Medical Center, Dallas, TX 75390, USA.
Seemann
Joachim
J
Orth
Kim
K
D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010587:Phagocytosis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D014735:Vibrio Infections / Q000382:microbiology*; D014736:Vibrio parahaemolyticus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*
D000071187:Autophagy-Related Protein 5; D001426:Bacterial Proteins; D008869:Microtubule-Associated Proteins; D019869:Phosphatidylinositol 3-Kinases; C502778:ATG5 protein, human