Intracellular Helicobacter pylori in gastric epithelial progenitors

Abstract

Helicobacter pylori is generally viewed as an extracellular pathogen. We have analyzed the tropism of H. pylori clinical isolates in a gnotobiotic transgenic mouse model of human chronic atrophic gastritis, a preneoplastic condition. These mice lack acid-producing parietal cells and have an amplified population of dividing gastric epithelial progenitors (GEPs) that express NeuAc␣2,3Gal␤1,4-glycans recognized by H. pylori adhesins. Scanning confocal and transmission electron microscopic studies of stomachs that had been colonized for 1 month or 1 year revealed intracellular bacterial collections (IBCs) in a small subset of multi-and oligopotential epithelial progenitors. Transmission electron microscopic and multilabel immunohistochemical analyses disclosed bacteria with several morphotypes, including spiral-shaped, in the cytoplasm and endosomes. Several stages in IBC evolution were documented, from a few solitary bacteria to consolidated populations in dividing and nondividing GEPs, to microorganisms traversing breaches in the GEP plasma cell membrane. IBC formation was not a unique feature of H. pylori strains isolated from patients with chronic atrophic gastritis. The notion that adult mammalian epithelial progenitors can function as a repository for H. pylori broadens the view of host habitats available to this and perhaps other pathogens.adult mammalian epithelial progenitors ͉ bacterial pathogenesis ͉ intracellular bacterial communities ͉ gnotobiotic mice ͉ chronic atrophic gastritis

Invasion and Multiplication of Helicobacter pylori in Gastric Epithelial Cells and Implications for Antibiotic Resistance

“…3a). Intracellular H. pylori collections have been demonstrated in a small subset of gastric epithelial progenitors after infection of acid-producing parietal cell-deficient mice (16,17) or in preneoplastic or cancer tissue (15,23). H. pylori bacteria were detectable in endosome, cytoplasm vacuole, or plasma membrane or in membrane-associated coccoid form, which is consistent with our observation that H. pylori is replicating in the autophagosome or plasma membrane.…”

Inflammation, atrophy, and gastric cancer

“…Although about 10% of H. pylori can adhere to gastric epithelial cells, organisms are rarely found intracellularly (31)(32)(33). Adherence of H. pylori to the gastric epithelium is a complicated process that involves a number of bacterial cell-surface receptors, including the Lewis B-bind- ing (Le b -binding) adhesin BabA (34), an outer membrane protein encoded by babA2 that binds the histo-blood group antigen Le b on the surface of epithelial cells.…”

Coadaptation of Helicobacter pylori and humans: ancient history, modern implications

“…The compensatory hypergastrinemia accompanying atrophy may also contribute, since gastrin promotes proliferation; transgenic hypergastrinemic mice develop accelerated cancer in response to other agents (78). A further theory, based on several lines of evidence (79,80), suggests that stem cells may be a direct target of H. pylori in the atrophic stomach, even though H. pylori are less numerous there than in the healthy stomach. To understand the origin of cancer cells in the Helicobacter-infected mouse model, marker studies were conducted in irradiated mice, who subsequently underwent bone marrow transplantation (81).…”