Helicobacter pylori images(Link to H. pylori research in work by Dr. Blaser, Dr. Kang, and Dr. Perez. )
H. pylori is among the most common bacteria that colonize humans. Nearly 50% of the world's adult population carries this organism. Our interest is toward the characterization of the human immune response to major H. pylori antigens, and to understand the role of virulence factors of H. pylori associated with different clinical outcomes (including peptic ulcer disease and gastric neoplasia). In that regard, we also are working to understand the nature of the association of H. pylori with gastric carcinoma.
Another area of interest in our current studies is to determine how H. pylori is acquired and to describe the early stages of the natural history of the colonization of children. These studies combine epidemiologic approaches with clinical and basic immunology, as well as using molecular probes and amplification techniques for analysis.
|Petri dish with Helicobacter pylori growth at 48 hours on Trypticase Soy Agar (TSA) + 5% sheep blood. The bacteria was isolated from a gastric biopsy at the NY Harbor VA Medical Center.||[ click on images to view enlargement ]|
|H. pylori colonization increases risk for development of peptic ulcer disease and gastric adenocarcinoma. Conversely, its presence appears to protect against certain diseases of the esophagus. A focus of this laboratory is to explore the biology of H. pylori colonization and the nature of the interactions that lead to (or protect from) disease.
Several avenues are being approached. We are examining the variation in particular oligosaccharide (Lewis) antigens on the H. pylori cell surface and the nature of the host forces that select for cells of particular phenotypes.
Disciplines involved include molecular biology, genetics, and mathematics. We are using transgenic and knockout mice to test hypotheses related to both host factors and bacterial evolution.
Other projects relate to restriction-modification systems that act as barriers to horizontal gene transfer, and to a metastable "pathogenicity island" in the H. pylori genome (cag island). A third area of work relates to recombination, endogenous mutation, and DNA repair to understand their roles and regulation in the generation of diversity.
|Electron photomicrograph of Helicobacter pylori colonizing the stomach of a human volunteer who ingested the organism as part of an experimental inoculation. The spiral microaerophilic bacteria live in the mucus layer that overlays the gastric epithelium.
Photo copyright, Martin J. Blaser, 1989.
|H. pylori adherence to gastric mucosa epithelium|
|Steiner stain of gastric antral biopsies from an H. pylori–positive patient (left) and an H. pylori–negative patient (right; photomicrographs courtesy of Zhiheng Pei, M.D., Ph.D.). H pylori positivity is associated with risk of gastric cancer, whereas H. pylori negativity is associated with risk of EAC. The presence of H. pylori (left) is indicated by the dark curved bacilli in the mucus layer adjacent to the epithelial cell surfaces. The H. pylori–positive biopsy shows deeper staining of the epithelial cells, indicating tissue reactivity, and the lamina propria shows increased mononuclear cell numbers (compared with the H. pylori–negative biopsy). The biopsies were formalin fixed and paraffin embedded, and both images have the same magnification (bar, 50 μm).|