Dual RNA sequencing of Helicobacter pylori and host cell transcriptomes reveals ontologically distinct host-pathogen interaction
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AbstractHelicobacter pylori is a highly successful pathogen that poses a substantial threat to human health. However, the dynamic interaction between H. pylori 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 (cagA)-modulated bacterial adaption strategy by enhancing the expression of ATP-binding cassette transporter-related genes, metQ and HP_0888, upon coculturing with human gastric epithelial cells. We observed a general repression of electron transport-associated genes by cagA, 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 H. pylori infection. Moreover, we demonstrated a protective effect of gastric H. pylori colonization against chronic dextran sulfate sodium (DSS)-induced colitis. Mechanistically, we identified a cluster of propionic and butyric acid-producing bacteria, Muribaculaceae, selectively enriched in the colons of H. pylori-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 H. pylori during its dynamic interaction with gastric epithelial cells and provides new insights into strategies through which H. pylori promotes infection and pathogenesis in the human gastric epithelium.
All Author(s) ListHu W., Zhai Z.Y., Huang Z.Y., Chen Z.M., Zhou P., Li X.X., Yang G.H., Bao C.J., You L.J., Cui X.B., Xia G.L., Ou Yang M.P., Zhang L., Kei Wu W.K., Li L.F., Zhang Y.X., Xiao Z.G., Gong W.
Journal namemSystems
Year2024
Month4
Volume Number9
Issue Number4
PublisherAmerican Society for Microbiology
eISSN2379-5077
LanguagesEnglish-United Kingdom
Keywordsoxidative phosphorylation, alternative splicing, ATP-binding cassette transporter, cytotoxin-associated genes A, dual RNA sequencing, Helicobacter pylori, inflammatory bowel disease

Last updated on 2024-10-10 at 15:40