Integrin but not CEACAM receptors are dispensable for Helicobacter pylori CagA translocation

Zhao, Qing; Busch, Benjamin; Jimenez-Soto, Luisa Fernanda; Ishikawa-Ankerhold, Hellen; Massberg, Steffen; Terradot, Laurent; Fischer, Wolfgang und Haas, Rainer (2018): Integrin but not CEACAM receptors are dispensable for Helicobacter pylori CagA translocation.
In: PLOS Pathogens 14(10), e1007359

Abstract

Translocation of the Helicobacter pylori (Hp) cytotoxin-associated gene A (CagA) effector protein via the cag-Type IV Secretion System (cag-T4SS) into host cells is a hallmark of infection with Hp and a major risk factor for severe gastric diseases, including gastric cancer. To mediate the injection of CagA, Hp uses a membrane-embedded syringe-like molecular apparatus extended by an external pilus-like rod structure that binds host cell surface integrin heterodimers. It is still largely unclear how the interaction of the cag-T4SS finally mediates translocation of the CagA protein into the cell cytoplasm. Recently certain carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), acting as receptor for the Hp outer membrane adhesin HopQ, have been identified to be involved in the process of CagA host cell injection. Here, we applied the CRISPR/Cas9-knockout technology to generate defined human gastric AGS and KatoIII integrin knockout cell lines. Although confocal laser scanning microscopy revealed a co-localization of Hp and beta 1 integrin heterodimers on gastric epithelial cells, Hp infection studies using the quantitative and highly sensitive Hp beta-lactamase reporter system clearly show that neither beta 1 integrin heterodimers (alpha 1 beta 1, alpha 2 beta 1 or alpha 5 beta 1), nor any other a beta integrin heterodimers on the cell surface are essential for CagA translocation. In contrast, deletion of the HopQ adhesin in Hp, or the simultaneous knockout of the receptors CEACAM1, CEACAM5 and CEACAM6 in KatoIII cells abolished CagA injection nearly completely, although bacterial binding was only reduced to 50%. These data provide genetic evidence that the cag-T4SS-mediated interaction of Hp with cell surface integrins on human gastric epithelial cells is not essential for CagA translocation, but interaction of Hp with CEACAM receptors is facilitating CagA translocation by the cag-T4SS of this important microbe.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1553-7366
• Sprache: Englisch