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Authors: Mauricio R. Terebiznik, Deepa Raju, Cristina Lourdes Vázquez, Karl Torbricki, Reshma Kulkarni, Steven R. Blanke, Tamotsu Yoshimori, María Isabel Colombo and Nicola L. Jones

Mauricio R. Terebiznik

Cell Biology Program; Hospital for Sick Children; Toronto, Ontario, Canada; Department of Cell and Systems Biology; University of Toronto; Scarborough, Ontario, Canada

Deepa Raju

Cell Biology Program; Hospital for Sick Children; Toronto, Ontario, Canada; Departments of Paediatrics and Physiology; University of Toronto; Toronto, Ontario, Canada

Cristina Lourdes Vázquez

Laboratorio de Biología Celular y Molecular; Instituto de Histología y Embriología (IHEM); Facultad de Ciencias Médicas; Universidad Nacional de Cuyo-CONICET; Mendoza, Argentina

Karl Torbricki

Cell Biology Program; Hospital for Sick Children; Toronto, Ontario, Canada; Departments of Paediatrics and Physiology; University of Toronto; Toronto, Ontario, Canada

Reshma Kulkarni

Department of Microbiology and Institute for Genomic Biology; University of Illinois; Urbana, Illinios USA

Steven R. Blanke

Department of Microbiology and Institute for Genomic Biology; University of Illinois; Urbana, Illinios USA

Tamotsu Yoshimori

Department of Cellular Regulation; Research Institute for Microbial Diseases; Osaka University; Suita, Osaka, Japan

María Isabel Colombo

Laboratorio de Biología Celular y Molecular; Instituto de Histología y Embriología (IHEM); Facultad de Ciencias Médicas; Universidad Nacional de Cuyo-CONICET; Mendoza, Argentina

Nicola L. Jones

Corresponding author: nicola.jones@sickkids.ca
Cell Biology Program; Hospital for Sick Children; Toronto, Ontario, Canada; Departments of Paediatrics and Physiology; University of Toronto; Toronto, Ontario, Canada

Abstract:
Host cell responses to Helicobacter pylori infection are complex and incompletely understood. Here, we report that autophagy is induced within human-derived gastric epithelial cells (AGS) cells in response to H. pylori infection. These autophagosomes were distinct and different from the large vacuoles induced during H. pylori infection. Autophagosomes were detected by transmission electron microscopy, conversion of LC3-I to LC3-II, GFP-LC3 recruitment to autophagosomes, and depended on Atg5 and Atg12. The induction of autophagy depended on the vacuolating cytotoxin (VacA) and, moreover, VacA was sufficient to induce autophagosome formation. The channel forming activity of VacA was necessary for inducing  autophagy.  Intracellular VacA  partially co-localized with GFP-LC3, indicating that the toxin associates with autophagosomes. The inhibition of autophagy increased the stability of intracellular VacA, which in turn resulted in enhanced toxin-mediated cellular vacuolation. These findings suggest that the induction of autophagy by VacA may represent a host mechanism to limit toxin-induced cellular damage.

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