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

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 () and William K. K. Wu ()
Additional contact information
Judeng Zeng: The Chinese University of Hong Kong, Hong Kong Special Administrative Region
Chuan Xie: The Chinese University of Hong Kong, Hong Kong Special Administrative Region
Ziheng Huang: The Chinese University of Hong Kong, Hong Kong Special Administrative Region
Chi H. Cho: Southwest Medical University
Hung Chan: The Chinese University of Hong Kong, Hong Kong Special Administrative Region
Qing Li: The Chinese University of Hong Kong, Hong Kong Special Administrative Region
Hassan Ashktorab: Howard University
Duane T. Smoot: Meharry Medical College
Sunny H. Wong: Nanyang Technological University
Jun Yu: The Chinese University of Hong Kong, Hong Kong Special Administrative Region
Wei Gong: Shenzhen Hospital, Southern Medical University
Cong Liang: Xiamen University
Hongzhi Xu: Xiamen University
Huarong Chen: The Chinese University of Hong Kong, Hong Kong Special Administrative Region
Xiaodong Liu: The Chinese University of Hong Kong, Hong Kong Special Administrative Region
Justin C. Y. Wu: The Chinese University of Hong Kong, Hong Kong Special Administrative Region
Margaret Ip: CUHK Shenzhen Research Institute
Tony Gin: The Chinese University of Hong Kong, Hong Kong Special Administrative Region
Lin Zhang: The Chinese University of Hong Kong, Hong Kong Special Administrative Region
Matthew T. V. Chan: The Chinese University of Hong Kong, Hong Kong Special Administrative Region
Wei Hu: Shenzhen Hospital, Southern Medical University
William K. K. Wu: The Chinese University of Hong Kong, Hong Kong Special Administrative Region

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract The role of N6-methyladenosine (m6A) modification of host mRNA during bacterial infection is unclear. Here, we show that Helicobacter pylori infection upregulates host m6A methylases and increases m6A levels in gastric epithelial cells. Reducing m6A methylase activity via hemizygotic deletion of methylase-encoding gene Mettl3 in mice, or via small interfering RNAs targeting m6A methylases, enhances H. pylori colonization. We identify LOX-1 mRNA as a key m6A-regulated target during H. pylori infection. m6A 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 m6A modification of host LOX-1 mRNA contributes to protection against H. pylori infection by downregulating LOX-1 and thus reducing H. pylori adhesion.

Date: 2024
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DOI: 10.1038/s41467-024-44860-9

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