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

Overview

Journal Toxins (Basel)

Publisher MDPI

Specialty Toxicology

Date 2019 Nov 17

PMID 31731531

Citations 2

Authors

Vittorio Necchi

Vittorio Ricci

Patrizia Sommi

Enrico Solcia

Affiliations

Soon will be listed here.

Abstract

A key role in the carcinogenic action of 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 -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 -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.

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