Transcriptomic remodeling of gastric cells by Helicobacter pylori outer membrane vesicles.

BACKGROUND: Outer membrane vesicles (OMVs) are spontaneously released by Gram-negative bacteria and influence bacteria-host interactions by acting as a delivery system for bacterial components and by interacting directly with host cells. Helicobacter pylori, a pathogenic bacterium that chronically colonizes the human stomach, also sheds OMVs, and their impact on bacterial-mediated diseases is still being elucidated. MATERIALS AND METHODS: Transcriptomic profiling of the human gastric cell line MKN74 upon challenge with H. pylori OMVs compared to control and infected cells was performed using the Ion AmpliSeq™ Transcriptome Human Gene Expression Panel to understand the gene expression changes that human gastric epithelial cells might undergo when exposed to H. pylori OMVs. RESULTS: H. pylori OMVs per se modify the gene expression profile of gastric epithelial cells, adding another layer of (gene) regulation to the already complex host-bacteria interaction. The most enriched pathways include those related to amino acid metabolism, mitogen-activated protein kinase signaling, autophagy, and ferroptosis, whereas the cell cycle, DNA replication, and DNA repair were the most downregulated. The transcriptomic changes induced by OMVs were mostly similar to those induced by the parental bacteria, likely amplifying the effects of the bacterium itself. CONCLUSIONS: Our data provide a valuable portrayal of the transcriptomic remodeling of gastric cells induced by H. pylori OMVs. It demonstrates the breadth of cellular pathways and genes affected by OMVs, most previously unreported, which can be further dissected for the underlying molecular mediators and explored to understand the pathobiology of the full spectrum of H. pylori-mediated diseases.