Expression of UreI is required for intragastric transit and colonization of gerbil gastric mucosa by Helicobacter pylori.
Helicobacter pylori colonizes the antral mucosa of the human stomach. There is a controversy as to whether the microorganism is exposed to acidity in its ecological niche. In vitro, the microorganism requires urease for gastric colonization and survival at pH < 4.0. UreI encodes an acid activated urea channel enabling urea access to intrabacterial urease at acidic pH. UreI is also necessary for survival at pH < 4.0. However, the role of UreI for both intragastric transit and colonization of the epithelial gastric mucosa has never been analyzed in detail. We therefore infected gerbils, whose intragastric pH and response to infection resemble those of man, with H. pylori G1.1 wild type bacteria and their corresponding isogenic ureI mutants. Inhibitors of gastric acid secretion and colonization were used for manipulation of gastric pH. Gastric colonization was determined by urease assay and PCR. Gastric pH was measured with pH electrodes. Whereas H. pylori wild type or ureI complemented ureI knockout bacteria colonized the antrum, ureI deletion mutants were unable to colonize. However, continuous inhibition of acid secretion resulted in gastric colonization by the ureI mutants, as also observed with the wild type strain. Restoration of acid secretion resulted in eradication of ureI mutants but not wild type bacteria. The data show that ureI is essential for both gastric transit after inoculation and mucosal colonization in the untreated stomach. The eradication of ureI mutants following restoration of acid secretion suggests that the organism is exposed to pH < 4.0 at the surface of the antral mucosa and that UreI provides a target for specific monotherapy of H. pylori infections.
Mollenhauer-Rektorschek
Marina
M
ALTANA Pharma, Department of Functional Genomics, Konstanz, Germany.
Hanauer
Guido
G
Sachs
George
G
Melchers
Klaus
K
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D005744:Gastric Acid / Q000378:metabolism; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000382:microbiology*; D005849:Gerbillinae; D016480:Helicobacter pylori / Q000201:enzymology* / Q000472:pathogenicity; D008297:Male; D026901:Membrane Transport Proteins; D017494:Proton Pumps / Q000502:physiology
D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D017494:Proton Pumps; C114527:UreI protein, Helicobacter pylori