How Helicobacter pylori senses, targets and interacts with the gastric epithelium

Abstract

SummaryHelicobacter pylori is a human-specific pathogen that chronically infects about 50% of the world's population. After travelling through the harsh environment of the stomach lumen, H. pylori colonizes the mucosal surface and within the glands of the human stomach. During colonization, H. pylori uses motility and its chemotaxis signalling system to sense the environment to reach the gastric epithelium for colonization, where it is able to attach to the epithelial surface. The H. pylori population inside the stomach contains a subgroup of bacteria that are attached to the gastric epithelium and a larger subgroup of nonattached bacteria that are freely swimming. To establish a tight interaction between H. pylori and epithelial cells, the bacterium produces a variety of adhesins and delivers virulence factors. These lead to alterations in the host signalling pathways, inducing proinflammatory responses, apoptosis, uncontrolled cell proliferation, and eventually peptic ulcers and gastric cancer. To prevent disease and find a vaccine or better treatments, it is crucial to understand how H. pylori is able to sense its niche for chronic infection inside the stomach and how its virulence factors interact with the epithelial target cells.

A proposed role for diffusible signal factors in the biofilm formation and morphological transformation of Helicobacter pylori

“…Coccoid forms, which are exposed to stimulatory/ stress-inducing factors that occur in this environment and are induced by AI-2 secreted by the gastric microflora, are converted from the spherical to the spiral form (9)(10)(11)13,14,22,29,48,49). The possible lack of AI-2 stimulation causes H. pylori to remain in the coccoid form with the decreased ability to adhere to and penetrate the mucosa, potentially contributing to the removal of this bacterium from the human body (6). Spiral forms actively seek the gastric mucosa to protect against the low pH of the stomach environment.…”

“…This is supported by chemotaxis away from AI-2 and protons and towards nutrients (amino acids and metal ions), urea, and HCO 3 -. In addition, the spiral shape enables effective penetration of mucin (6,22,31). After bacterial proliferation in the gastric mucosa, microorganisms enter the stationary phase accompanied by a decrease in AI-2 concentration and an increase in DSFs autoinductive activity.…”

“…autoaggregative behavior and biofilm formation (35,38,39,45,46). Reduction of DSFs activity and an increase in AI-2 concentration results in the transformation of some coccoid H. pylori forms to the spiral morphotype, followed by chemorepulsion from the AI-2 source and migration in search of new niches in the gastric environment (6,17,(30)(31)(32)44).…”

“…The lowest pH is in the lumen of the stomach, but it becomes near neutral in the mucosa. H. pylori enters the stomach through the mouth and rapidly colonizes the mucosa of both the gastric body and antrum (6). Because the colonization step is crucial for H. pylori, this bacterium exhibits a number of adaptive features that facilitate the smooth operation of this process.…”

Recent Advances and Future Prospects in Bacterial and Archaeal Locomotion and Signal Transduction

“…This organism has three transmembrane chemoreceptors (TlpA, TlpB, and TlpC) and one cytoplasmic chemoreceptor (TlpD) that together feed into a single chemosensory pathway (44). Mounting evidence suggests that signaling through all four chemoreceptors is necessary for efficient colonization of the gastric epithelium (45). It has been shown that H. pylori exhibits chemotaxis toward metabolites emanating from the human gastric epithelium and that urea is the primary host-derived metabolite that attracts the bacterium (46).…”