The spatial orientation of Helicobacter pylori in the gastric mucus

Abstract

The highly motile human pathogen Helicobacter pylori lives deep in the gastric mucus layer. To identify which chemical gradient guides the bacteria within the mucus layer, combinations of luminal perfusion, dialysis, and ventilation were used to modify or invert transmucus gradients in anaesthetized Helicobacterinfected mice and Mongolian gerbils. Neither changes in lumen or arterial pH nor inversion of bicarbonate͞CO2 or urea͞ammonium gradients disturbed Helicobacter orientation. However, elimination of the mucus pH gradient by simultaneous reduction of arterial pH and bicarbonate concentration perturbed orientation, causing the bacteria to spread over the entire mucus layer. H. pylori thus uses the gastric mucus pH gradient for chemotactic orientation. Helicobacter pylori, a motile Gram-negative human pathogen that causes gastritis and duodenal and gastric ulcers and increases the risk of gastric cancer (1), lives within the gastric mucus layer. The majority of bacteria are located deep in the mucus, close to the surface of the epithelium. The mucus is continuously secreted in the glands and by surface epithelial cells and is degraded at the luminal surface (2). Because of this rapid mucus turnover, the bacteria need motility and spatial orientation to avoid being carried into the lumen, where the acidic pH inhibits growth and paralyzes motility (3, 4). Orientation therefore plays a central role in acute colonization and the chronic persistence of H. pylori.Motile bacteria sense chemical gradients by means of chemoreceptor proteins and relay the information to the flagellar motor (5). In the case of H. pylori, it must be a chemical gradient in the gastric mucus layer that guides the bacteria. Within the mucus layer, diffusion is effectively restricted, so that the concentration of most substances entering the mucus from the epithelial surface will remain constant through the entire width of the layer. Despite this, at least three chemical gradients are known to exist here: a proton (pH) gradient (2, 6), a bicarbonate͞CO 2 gradient (7,8), and, in the Helicobacter-infected mucosa, a urea͞ammonium gradient (9) created by bacterial urease. We hypothesized that H. pylori may use one or several of these transmucus gradients for orientation in vivo.We have previously developed a method to precisely determine the distribution and colonization density of Helicobacter felis in the gastric mucus of mice in vivo (3). This method uses a micromanipulator-controlled sampling device (10) to extract nanoliter samples from the mucus and mucosa of anesthetized animals. After immediate immobilization of the bacteria by cooling, the density and distribution of the bacteria can be studied by digital image processing.To identify gradients involved in the orientation of Helicobacter spp., we inverted or modified individual gradients in anesthetized H. pylori-infected Mongolian gerbils or H. felisinfected mice and studied the effect of these changes on the distribution of bacteria in the mucus layer. The data show that gastric Helicob...

A supplemented soft agar chemotaxis assay demonstrates the Helicobacter pylori chemotactic response to zinc and nickel

“…H. pylori infection can cause ulcers and gastric cancers (Yamada et al, 1994;Parsonnet et al, 1991;Uemura et al, 2001). One well-established H. pylori chemotactic signal is pH (Croxen et al, 2006;Schreiber et al, 2004). Acid chemotaxis fits well with H. pylori's gastric mucosal habitat, which is much less acidic than the lumen Baumgartner & Montrose, 2004;Chu et al, 1999;Ross et al, 1982;Schreiber & Scheid, 1997;Williams & Turnberg, 1982).…”

“…There are a handful of reported H. pylori chemotaxis-active compounds. Urea is one such chemoattractant (Cerda et al, 2003;Mizote et al, 1997;Worku et al, 2004), although H. pylori mucosal localization is not affected in vivo when the urea/ammonium gradient is altered (Schreiber et al, 2004). Other reported attractants include bicarbonate (Cerda et al, 2003;Mizote et al, 1997), NaCl (Mizote et al, 1997), cholesterol (Wunder et al, 2006), and the amino acids aspartate, serine and arginine (Cerda et al, 2003).…”

Role for α- l -fucosidase in the control of Helicobacter pylori -infected gastric cancer cells

“…A considerable proportion of H. pylori in the stomach is located at the epithelial mucosa (22) where there are various fucose-containing oligosaccharides including Lewis antigens. To determine if H. pylori acquires L-fucose from host cells, similar to the interaction between B. thetaiotaomicron and small intestine cells (20), the click chemistry-based fluorogenic labeling method developed by Wong and coworkers (23) was applied to detect fucosylated glycoconjugates.…”

Helicobacter pylori—Associated Dyspepsia in Paediatrics

“…In the early stages of colonization, H. pylori seeks parts of the stomach with higher pH, such as the antrum (the distal part of the stomach). Indeed, this bacterium uses the pH gradient as chemotactic signal to achieve regions of neutral pH, since its spatial orientation is lost in the absence of the mucus pH gradient [41]. Thus, the acid-producing parietal cells may protect the corpus region from initial invasion.…”