Reduced lysosomal clearance of autophagosomes promotes survival and colonization of Helicobacter pylori
Publication in refereed journal


摘要Evasion of autophagy is key for intracellular survival of bacteria in host cells, but its involvement in persistent infection by Helicobacter pylori, a bacterium identified to invade gastric epithelial cells, remains obscure. The aim of this study was to functionally characterize the role of autophagy in H. pylori infection. Autophagy was assayed in H. pylori‐infected human gastric epithelium and the functional role of autophagy was determined via genetic or pharmacological ablation of autophagy in mouse and cell line models of H. pylori infection. Here, we showed that H. pylori inhibited lysosomal function and thereby promoted the accumulation of autophagosomes in gastric epithelial cells. Importantly, inhibiting autophagosome formation by pharmacological inhibitors or genetic ablation of BECN1 or ATG5 reduced H. pylori intracellular survival, whereas inhibition of lysosomal functions exerted an opposite effect. Further experiments demonstrated that H. pylori inhibited lysosomal acidification and the retrograde trafficking of mannose‐6‐phosphate receptors, both of which are known to positively regulate lysosomal function. We conclude that H. pylori subverts autophagy into a pro‐survival mechanism through inhibition of lysosomal clearance of autophagosomes. Disruption of autophagosome formation offers a novel strategy to reduce H. pylori colonization in human stomachs.
著者Lin Zhang, Wei Hu, Chi H Cho, Francis KL Chan, Jun Yu, J Ross Fitzgerald, Cynthia KY Cheung, Zhan G Xiao, Jing Shen, Long F Li, Ming X Li, Justin CY Wu, Thomas KW Ling, Jason YK Chan, Ho Ko, Gary Tse, Siew C Ng, Sidney Yu, Maggie HT Wang, Tony Gin, Hassan Ashktorab, Duane T Smoot, Sunny H Wong, Matthew TV Chan, William KK Wu
期刊名稱The Journal of Pathology
頁次432 - 444

上次更新時間 2021-17-09 於 00:04