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

Carmen Aguilar, Mindaugas Pauzuolis, Malvika Pompaiah, Ehsan Vafadarnejad, Panagiota Arampatzi, Mara Fischer, Dominik Narres, Mastura Neyazi, Özge Kayisoglu, Thomas Sell, Nils Blüthgen, Markus Morkel, Armin Wiegering, Christoph-Thomas Germer, Stefan Kircher, Andreas Rosenwald, Antoine-Emmanuel Saliba () and Sina Bartfeld ()
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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

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33165-4

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DOI: 10.1038/s41467-022-33165-4

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