Dual RNA sequencing of Helicobacter pylori and host cell transcriptomes reveals ontologically distinct host-pathogen interaction

Media type: E-Article
Title: Dual RNA sequencing of Helicobacter pylori and host cell transcriptomes reveals ontologically distinct host-pathogen interaction
Contributor: Hu, Wei; Zhai, Zhi Yong; Huang, Zhao Yu; Chen, Ze Min; Zhou, Ping; Li, Xia Xi; Yang, Gen Hua; Bao, Chong Ju; You, Li Juan; Cui, Xiao Bing; Xia, Gui Li; Ou Yang, Mei Ping; Zhang, Lin; Wu, William Ka Kei; Li, Long Fei; Zhang, Yu Xuan; Xiao, Zhan Gang; Gong, Wei
imprint: American Society for Microbiology, 2024
Published in: mSystems
Language: English
DOI: 10.1128/msystems.00206-24
ISSN: 2379-5077
Origination:
Footnote:
Description: <jats:title>ABSTRACT</jats:title> <jats:sec> <jats:title /> <jats:p> <jats:italic>Helicobacter pylori</jats:italic> is a highly successful pathogen that poses a substantial threat to human health. However, the dynamic interaction between <jats:italic>H. pylori</jats:italic> and the human gastric epithelium has not been fully investigated. In this study, using dual RNA sequencing technology, we characterized a cytotoxin-associated gene A ( <jats:italic>cagA</jats:italic> )-modulated bacterial adaption strategy by enhancing the expression of ATP-binding cassette transporter-related genes, <jats:italic>metQ</jats:italic> and <jats:italic>HP_0888</jats:italic> , upon coculturing with human gastric epithelial cells. We observed a general repression of electron transport-associated genes by <jats:italic>cagA</jats:italic> , leading to the activation of oxidative phosphorylation. Temporal profiling of host mRNA signatures revealed the downregulation of multiple splicing regulators due to bacterial infection, resulting in aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to <jats:italic>H. pylori</jats:italic> infection. Moreover, we demonstrated a protective effect of gastric <jats:italic>H. pylori</jats:italic> colonization against chronic dextran sulfate sodium (DSS)-induced colitis. Mechanistically, we identified a cluster of propionic and butyric acid-producing bacteria, <jats:italic>Muribaculaceae</jats:italic> , selectively enriched in the colons of <jats:italic>H. pylori</jats:italic> -pre-colonized mice, which may contribute to the restoration of intestinal barrier function damaged by DSS treatment. Collectively, this study presents the first dual-transcriptome analysis of <jats:italic>H. pylori</jats:italic> during its dynamic interaction with gastric epithelial cells and provides new insights into strategies through which <jats:italic>H. pylori</jats:italic> promotes infection and pathogenesis in the human gastric epithelium. </jats:p> </jats:sec> <jats:sec> <jats:title>IMPORTANCE</jats:title> <jats:p> Simultaneous profiling of the dynamic interaction between <jats:italic>Helicobacter pylori</jats:italic> and the human gastric epithelium represents a novel strategy for identifying regulatory responses that drive pathogenesis. This study presents the first dual-transcriptome analysis of <jats:italic>H. pylori</jats:italic> when cocultured with gastric epithelial cells, revealing a bacterial adaptation strategy and a general repression of electron transportation-associated genes, both of which were modulated by cytotoxin-associated gene A ( <jats:italic>cagA</jats:italic> ). Temporal profiling of host mRNA signatures dissected the aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to <jats:italic>H. pylori</jats:italic> infection. We demonstrated a protective effect of gastric <jats:italic>H. pylori</jats:italic> colonization against chronic DSS-induced colitis through both <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic> experiments. These findings significantly enhance our understanding of how <jats:italic>H. pylori</jats:italic> promotes infection and pathogenesis in the human gastric epithelium and provide evidence to identify targets for antimicrobial therapies. </jats:p> </jats:sec>
Access State: Open Access

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