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Helicobacter pylori shows tropism to gastric differentiated pit cells dependent on urea chemotaxis

Author

Listed:
  • Carmen Aguilar

    (Julius Maximilians University of Würzburg)

  • Mindaugas Pauzuolis

    (Julius Maximilians University of Würzburg)

  • Malvika Pompaiah

    (Julius Maximilians University of Würzburg)

  • Ehsan Vafadarnejad

    (Helmholtz-Centre for Infection Research (HZI))

  • Panagiota Arampatzi

    (University of Würzburg)

  • Mara Fischer

    (Julius Maximilians University of Würzburg)

  • Dominik Narres

    (Julius Maximilians University of Würzburg)

  • Mastura Neyazi

    (Julius Maximilians University of Würzburg)

  • Özge Kayisoglu

    (Julius Maximilians University of Würzburg)

  • Thomas Sell

    (Charité Universitätsmedizin Berlin)

  • Nils Blüthgen

    (Charité Universitätsmedizin Berlin)

  • Markus Morkel

    (Charité Universitätsmedizin Berlin)

  • Armin Wiegering

    (University Hospital of Würzburg)

  • Christoph-Thomas Germer

    (University Hospital of Würzburg)

  • Stefan Kircher

    (Julius Maximilian University of Würzburg and Comprehensive Cancer Center Mainfranken)

  • Andreas Rosenwald

    (Julius Maximilian University of Würzburg and Comprehensive Cancer Center Mainfranken)

  • Antoine-Emmanuel Saliba

    (Helmholtz-Centre for Infection Research (HZI))

  • Sina Bartfeld

    (Julius Maximilians University of Würzburg
    Technische Universität Berlin and Charité–Universitätsmedizin Berlin
    Technische Universität Berlin)

Abstract

The human gastric epithelium forms highly organized gland structures with different subtypes of cells. The carcinogenic bacterium Helicobacter pylori can attach to gastric cells and subsequently translocate its virulence factor CagA, but the possible host cell tropism of H. pylori is currently unknown. Here, we report that H. pylori preferentially attaches to differentiated cells in the pit region of gastric units. Single-cell RNA-seq shows that organoid-derived monolayers recapitulate the pit region, while organoids capture the gland region of the gastric units. Using these models, we show that H. pylori preferentially attaches to highly differentiated pit cells, marked by high levels of GKN1, GKN2 and PSCA. Directed differentiation of host cells enable enrichment of the target cell population and confirm H. pylori preferential attachment and CagA translocation into these cells. Attachment is independent of MUC5AC or PSCA expression, and instead relies on bacterial TlpB-dependent chemotaxis towards host cell-released urea, which scales with host cell size.

Suggested Citation

  • Carmen Aguilar & Mindaugas Pauzuolis & Malvika Pompaiah & Ehsan Vafadarnejad & Panagiota Arampatzi & Mara Fischer & Dominik Narres & Mastura Neyazi & Özge Kayisoglu & Thomas Sell & Nils Blüthgen & Mar, 2022. "Helicobacter pylori shows tropism to gastric differentiated pit cells dependent on urea chemotaxis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33165-4
    DOI: 10.1038/s41467-022-33165-4
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    References listed on IDEAS

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