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69 HELICOBACTER PYLORI TRIGGERS AUTOPHAGY IN INVADED CELLS MR Terebiznik, CL Vazquez1, K Tobricki, MI Colombo, NL Jones Autophagy is an evolutionarily conserved mechanism for the degradation of cellular components in the cytoplasm. It has multiple physiological functions including protein degradation, organelle turnover and autophagic type II cell death. Although bacteria and viruses are vulnerable to autophagy, several intracellular pathogens have developed strategies to utilize this pathway for their own benefit.
Infection, Injury, Immunity and Repair Program, Hospital for Sick Children, Departments of Paediatrics and Physiology, University of Toronto, Toronto, ON. 1IHEM, Faculty of Medical Science, UNC-CONICET, Mendoza, Argentina
H pylori colonizes the gastric epithelium of at least 50% of the world's population playing a causative role in the development of chronic gastritis, peptic ulcers, and gastric adenocarcinoma. Current evidence indicates that H pylori can invade epithelial cells in the gastric mucosa and survive inside large vacuolar compartments. However, relatively little is known about the biology of H pylori invasion and survival in host cells.
Our results demonstrate that H pylori containing vacuoles originate through the fusion of late endosomal-lysosomal organelles by a mechanism based on the ability of the VacA toxin to hijack the small GTPase Rab7. Rab7 is a key component of the mechanism that regulates the cellular endocytic pathway. We observed that the scission of Rab7 from its functional locations efficiently disrupts the host's metabolism. We therefore hypothesized that H pylori could induce a nutritional stress that triggers autophagy. To assess this possibility, we monitored the outcome of autophagy by expressing the autophagic protein marker LC3 in AGS cells. H pylori infection caused the recruitment of GFP-LC3 to a subpopulation of intracellular compartments. The phenotype clearly indicates the engagement of autophagy during AGS cell invasion by H pylori.
Our results describe a novel interaction of H pylori with the host cell. Since modulation of autophagy has been linked with carcinogenesis these findings may have relevance for the development of H pylori associated pathologies.