Intracellular niches for extracellular bacteria: lessons from Helicobacter pylori

Abstract

Helicobacter pylori colonizes the gastric epithelium of humans and plays a causative role in peptic ulcer disease and perhaps gastric cancer. H. pylori proliferates in the mucus layer over the epithelium and is not cleared by the host immune response. Although the mucus layer is the major reservoir of H. pylori in vivo, a growing body of evidence suggests that H. pylori can persist in multiple intracellular locales. Clinical isolates of H. pylori invade epithelial monolayers at least as well as Shigella. The intracellular organisms are cytotoxic, and bacterial microcolonies form on the exposed basement membrane. Both mononuclear phagocytes and neutrophils phagocytose unopsonized H. pylori. However, the internalized organisms are not killed efficiently and our recent data suggest that H. pylori disrupts phagosome maturation. Collectively, the data support the hypothesis that intracellular H. pylori represent a reservoir of organisms that contributes to bacterial persistence, host tissue damage, and treatment failure. J. Leukoc. Biol. 66: 753-756; 1999.

Helicobacter pylori Infection in a Pig Model Is Dominated by Th1 and Cytotoxic CD8+T Cell Responses

“…Although initially considered exclusively an extracellular bacterium, H. pylori also exploits intracellular niches in its host (44). Several studies have demonstrated that H. pylori can persist in hepatocytes (45) and replicate in macrophages (46) and bone marrow-derived dendritic cells (17) as well as gastric epithelial cells in vitro, thus providing evidence for its role as a facultative intracellular organism with the ability to reside, replicate, and successfully evade antibiotic therapy within host cells (47).…”

Regulation of Vacuolar pH and Its Modulation by Some Microbial Species

“…The V-ATPase is a large multisubunit complex that approaches a molecular mass of 10 3 kDa. Grossly, the structure of V-ATPases can be divided into the following two major functional domains: a 570-kDa peripheral subcomplex, known as V 1 , that is thought to bind and hydrolyze ATP, and an integral membrane subcomplex, termed V 0 , that serves as the pore through which protons traverse the bilayer (48,90,115). The rate of proton translocation is obviously dictated by the density of functional pumps in the organellar membrane, but other parameters also contribute importantly.…”

“…Remarkably, fewer than half of the internalized population of unopsonized H. pylori cells are destroyed (1). Killing is greatly enhanced when bacteria are opsonized with immunoglobulin G (3), implying that ϩ .…”

Helicobacter pyloriInduces Apoptosis of Macrophages in Association with Alterations in the Mitochondrial Pathway

“…For example, increased numbers of macrophages are observed in the mucosa of gastric biopsy specimens obtained from H. pylori-infected children and correlate with the severity of gastritis (71). Although H. pylori is considered an extracellular pathogen, clinical isolates have been shown to invade epithelial monolayers (1,66), and a recent study by Jhala et al (32) showed the bacterium residing in the lamina propria in infected individuals, suggesting a possible point of interaction between the bacterium and mucosal macrophages. Alternatively, H. pylori secretes soluble bacterial products that traverse the epithelial barrier and interact with macrophages in the lamina propria.…”