title: The secreted antigen, HP0175, of Helicobacter pylori links the unfolded protein response (UPR) to autophagy in gastric epithelial cells.
abstract: Autophagy is an intracellular catabolic process that is required to maintain cellular homeostasis. Pathogen-elicited host cell autophagy may favour containment of infection or may help in bacterial survival. Pathogens have developed the ability to modulate host autophagy. The secreted antigen HP0175, a peptidyl prolyl cis,trans isomerase of Helicobacter pylori, has moonlighting functions with reference to host cells. Here we show that it executes autophagy in gastric epithelial cells. Autophagy is dependent on the unfolded protein response (UPR) that activates the expression of PKR-like ER kinase (PERK). This is accompanied by phosphorylation of eukaryotic initiation factor 2α (eIF-2α) and transcriptional activation of ATF4 and CHOP. Knockdown of UPR-related genes inhibits the conversion of LC3I to LC3II, a marker of autophagy. The autophagy-inducing ability of H. pylori is compromised when cells are infected with an isogenic hp0175 mutant. Autophagy precedes apoptosis. Silencing of BECLIN1 augments cleavage of caspase 3 as well as apoptosis. Increased apoptosis of gastric epithelial cells is known to be linked to H. pylori-mediated gastric inflammation and carcinogenesis. To the best of our knowledge, this study provides the first demonstration of how HP0175 endowed with moonlighting functions links UPR-dependent autophagy and apoptosis during H. pylori infection.
authors.affiliation: Department of Chemistry, Bose Institute, Kolkata, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Halder
authors.forename: Chandreyee
authors.initials: C
authors.lastname: Datta
authors.forename: Ranjeet
authors.initials: R
authors.lastname: Kumar
authors.forename: Arun Kumar
authors.initials: AK
authors.lastname: Sharma
authors.forename: Joyoti
authors.initials: J
authors.lastname: Basu
authors.forename: Manikuntala
authors.initials: M
authors.lastname: Kundu
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology* / Q000502:physiology*; D016480:Helicobacter pylori / Q000502:physiology*; D054884:Host-Pathogen Interactions; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D015398:Signal Transduction; D056811:Unfolded Protein Response / Q000187:drug effects*
chemical_list: D000942:Antigens, Bacterial; D019696:Peptidylprolyl Isomerase