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

Author

Listed:
  • Judeng Zeng

    (The Chinese University of Hong Kong, Hong Kong Special Administrative Region
    The Chinese University of Hong Kong, Hong Kong Special Administrative Region
    CUHK Shenzhen Research Institute)

  • Chuan Xie

    (The Chinese University of Hong Kong, Hong Kong Special Administrative Region
    The Chinese University of Hong Kong, Hong Kong Special Administrative Region
    The First Affiliated Hospital of Nanchang University)

  • Ziheng Huang

    (The Chinese University of Hong Kong, Hong Kong Special Administrative Region
    The Chinese University of Hong Kong, Hong Kong Special Administrative Region
    CUHK Shenzhen Research Institute)

  • Chi H. Cho

    (Southwest Medical University)

  • Hung Chan

    (The Chinese University of Hong Kong, Hong Kong Special Administrative Region
    The Chinese University of Hong Kong, Hong Kong Special Administrative Region
    CUHK Shenzhen Research Institute)

  • Qing Li

    (The Chinese University of Hong Kong, Hong Kong Special Administrative Region
    The Chinese University of Hong Kong, Hong Kong Special Administrative Region
    CUHK Shenzhen Research Institute)

  • Hassan Ashktorab

    (Howard University
    Howard University
    Howard University Hospital, 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
    CUHK Shenzhen Research Institute
    The Chinese University of Hong Kong, Hong Kong Special Administrative Region)

  • Wei Gong

    (Shenzhen Hospital, Southern Medical University
    Southern Medical University)

  • Cong Liang

    (Xiamen University)

  • Hongzhi Xu

    (Xiamen University)

  • Huarong Chen

    (The Chinese University of Hong Kong, Hong Kong Special Administrative Region
    The Chinese University of Hong Kong, Hong Kong Special Administrative Region
    CUHK Shenzhen Research Institute)

  • Xiaodong Liu

    (The Chinese University of Hong Kong, Hong Kong Special Administrative Region
    CUHK Shenzhen Research Institute)

  • Justin C. Y. Wu

    (The Chinese University of Hong Kong, Hong Kong Special Administrative Region
    The Chinese University of Hong Kong, Hong Kong Special Administrative Region)

  • Margaret Ip

    (CUHK Shenzhen Research Institute
    The Chinese University of Hong Kong, Hong Kong Special Administrative Region)

  • 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
    The Chinese University of Hong Kong, Hong Kong Special Administrative Region
    CUHK Shenzhen Research Institute
    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
    CUHK Shenzhen Research Institute)

  • Wei Hu

    (Shenzhen Hospital, Southern Medical University
    Southern Medical University)

  • William K. K. Wu

    (The Chinese University of Hong Kong, Hong Kong Special Administrative Region
    The Chinese University of Hong Kong, Hong Kong Special Administrative Region
    CUHK Shenzhen Research Institute)

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.

Suggested Citation

  • 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 Li, 2024. "LOX-1 acts as an N6-methyladenosine-regulated receptor for Helicobacter pylori by binding to the bacterial catalase," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44860-9
    DOI: 10.1038/s41467-024-44860-9
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