LOX-1 acts as an N6-methyladenosine-regulated receptor for Helicobacter pylori by binding to the bacterial catalase

作者：Judeng Zeng, Chuan Xie, Ziheng Huang, Chi H. Cho, Hung Chan, Qing Li, Hassan Ashktorab, Duane T. Smoot, Sunny H. Wong, Jun Yu, Wei Gong, Cong Liang, Hongzhi Xu, Huarong Chen, Xiaodong Liu, Justin C. Y. Wu, Margaret Ip, Tony Gin, Lin Zhang, Matthew T.V. Chan, Wei Hu, William Ka Kei Wu · 发表于：Nature Communications · 年份：2024 · DOI：10.1038/s41467-024-44860-9 · 被引用次数：19 · 研究领域：Galectins and Cancer Biology、RNA modifications and cancer、Helicobacter pylori-related gastroenterology studies

Abstract The role of N 6 -methyladenosine (m 6 A) modification of host mRNA during bacterial infection is unclear. Here, we show that Helicobacter pylori infection upregulates host m 6 A methylases and increases m 6 A levels in gastric epithelial cells. Reducing m 6 A methylase activity via hemizygotic deletion of methylase-encoding gene Mettl3 in mice, or via small interfering RNAs targeting m 6 A methylases, enhances H. pylori colonization. We identify LOX-1 mRNA as a key m 6 A-regulated target during H. pylori infection. m 6 A modification destabilizes LOX-1 mRNA and reduces LOX-1 protein levels. LOX-1 acts as a membrane receptor for H. pylori catalase and contributes to bacterial adhesion. Pharmacological inhibition of LOX-1, or genetic ablation of Lox-1 , reduces H. pylori colonization. Moreover, deletion of the bacterial catalase gene decreases adhesion of H. pylori to human gastric sections. Our results indicate that m 6 A modification of host LOX-1 mRNA contributes to protection against H. pylori infection by downregulating LOX-1 and thus reducing H. pylori adhesion.