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Open AccessArticle

CagA Effector Protein in Helicobacter pylori-Infected Human Gastric Epithelium in Vivo: From Bacterial Core and Adhesion/Injection Clusters to Host Cell Proteasome-Rich Cytosol

1
Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy
2
Centro Grandi Strumenti, University of Pavia, 27100 Pavia, Italy
3
Pathologic Anatomy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Toxins 2019, 11(11), 618; https://doi.org/10.3390/toxins11110618
Received: 29 August 2019 / Revised: 14 October 2019 / Accepted: 24 October 2019 / Published: 25 October 2019
(This article belongs to the Special Issue Helicobacter pylori Infection–Inducement of Gastroenteric Diseases)
A key role in the carcinogenic action of Helicobacter pylori is played by the effector protein CagA, the first identified oncoprotein of the bacterial world. However, the present knowledge in regard to the bacterial injection of CagA into epithelial cells (through a type IV secretion system) and its intracellular fate is based primarily on experimental studies in vitro. Our study was aimed to investigate, in H. pylori-infected human gastric epithelium, CagA delivery and intracellular distribution in order to identify any in vivo counterpart of the cell injection mechanism described in vitro and any intracellular cytoplasmic site of preferential CagA distribution, thus shedding light on the natural history of CagA in vivo. By transmission electron microscopy and ultrastructural immunocytochemistry (which combine precise molecule localization with detailed analysis of bacterial-host cell interaction and epithelial cell ultrastructure), we investigated endoscopic biopsies of gastric antrum from H. pylori-infected dyspeptic patients. Our findings provide support for CagA direct injection into gastric epithelial cells at bacterial adhesion sites located on the lateral plasma membrane and for its cytosolic intracellular distribution with selective concentration inside peculiar proteasome-rich areas, which might be site not only of CagA degradation but also of CagA-promoted crucial events in gastric carcinogenesis. View Full-Text
Keywords: Helicobacter pylori; CagA; human gastric epithelium in vivo; host–pathogen interactions; gastric cancer; ultrastructural immunocytochemistry Helicobacter pylori; CagA; human gastric epithelium in vivo; host–pathogen interactions; gastric cancer; ultrastructural immunocytochemistry
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Necchi, V.; Ricci, V.; Sommi, P.; Solcia, E. CagA Effector Protein in Helicobacter pylori-Infected Human Gastric Epithelium in Vivo: From Bacterial Core and Adhesion/Injection Clusters to Host Cell Proteasome-Rich Cytosol. Toxins 2019, 11, 618.

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