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Open AccessArticle

A Novel Role for Helicobacter pylori Gamma-Glutamyltranspeptidase in Regulating Autophagy and Bacterial Internalization in Human Gastric Cells

1
Laboratory of Cellular Communication, Center for the Study of Exercise, Metabolism and Cancer (CEMC), Program in Cell and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
2
Advanced Center for Chronic Diseases (ACCDiS), Santiago 8380492, Chile
3
Laboratory of Oncology, Department of Hematology and Oncology, Pontificia Universidad Católica de Chile, Santiago 8330034, Chile
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(6), 801; https://doi.org/10.3390/cancers11060801
Received: 29 March 2019 / Revised: 23 April 2019 / Accepted: 26 April 2019 / Published: 10 June 2019
(This article belongs to the Special Issue Helicobacter pylori Associated Cancer)
The risk of developing gastric cancer is strongly linked to Helicobacter pylori (H. pylori) infection. Alternatively, autophagy is a conserved response that is important in cellular homeostasis and provides protection against bacterial infections. Although H. pylori is typically considered an extracellular bacterium, several reports indicate that it internalizes, possibly to avoid exposure to antibiotics. Mechanisms by which H. pylori manipulates host cell autophagic processes remain unclear and, importantly, none of the available studies consider a role for the secreted H. pylori virulence factor gamma-glutamyltranspeptidase (HpGGT) in this context. Here, we identify HpGGT as a novel autophagy inhibitor in gastric cells. Our experiments revealed that deletion of HpGGT increased autophagic flux following H. pylori infection of AGS and GES-1 gastric cells. In AGS cells, HpGGT disrupted the late stages of autophagy by preventing degradation in lysosomes without affecting lysosomal acidification. Specifically, HpGGT impaired autophagic flux by disrupting lysosomal membrane integrity, which leads to a decrease in lysosomal cathepsin B activity. Moreover, HpGGT was necessary for efficient internalization of the bacteria into gastric cells. This important role of HpGGT in internalization together with the ability to inhibit autophagy posits HpGGT as a key virulence factor in the development of gastric cancer. View Full-Text
Keywords: Helicobacter pylori; gamma-glutamyltranspeptidase; gastric cancer; autophagy; internalization Helicobacter pylori; gamma-glutamyltranspeptidase; gastric cancer; autophagy; internalization
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Bravo, J.; Díaz, P.; Corvalán, A.H.; Quest, A.F. A Novel Role for Helicobacter pylori Gamma-Glutamyltranspeptidase in Regulating Autophagy and Bacterial Internalization in Human Gastric Cells. Cancers 2019, 11, 801.

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