Intracellular Vacuolization Caused by the Urease of Helicobacter pylori

Xu, Jinghua; Goodwin, C. S.; Cooper, Margaret; Robinson, J. S.

doi:10.1093/infdis/161.6.1302

Cited by 67 publications

(33 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…pylori cytotoxicity only when the urea content of the cell incubation medium is in the range found for the human gastric juice. If this requirement is fulfilled, the large amounts of ammonia produced by bacterial urease greatly damage epithelial cells, as previously suggested by several investigations [21,25,29,30,37], It is well known that in vivo, gastric ammonia production is exclusively bacterial and that it is proportional to the amount of urea diffusing from blood to gastric juice. Hazell et al [38] dem onstrated that the urease activity of H. pylori is predictive of its virulence, and proposed that ammonia produced via the urease-dependent pathway may be cytotoxic to the mucosa [39].…”

Section: Discussionmentioning

confidence: 83%

Significance of Ammonia in the Genesis of Gastric Epithelial Lesions Induced by <i>Helicobacter pylori:</i> An in vitro Study with Different Bacterial Strains and Urea Concentrations

Sommi

Ricci²,

Fiocca

et al. 1996

Digestion

View full text Add to dashboard Cite

Two Helicobacter pylori products cause cell damage both in vivo and in vitro: ammonia, from bacterial urease activity, and a vacuolating toxin named VacA. In this in vitro study, the vacuolating effect of H. pylori broth culture filtrate from a VacA-positive/urease-positive strain is compared with that of a VacA-negative/urease-positive strain and a VacA-negative/urease-negative strain. The effect of VacA and ammonia was evaluated with and without addition of 10 mM urea, a physiological concentration for the human stomach, and with and without addition of 0.5 mg/ml acetohydroxamic acid (AHA), an urease inhibitor. Our data show that: (1) both urease-positive H. pylori strains caused cell vacuolation in the absence of urea, the VacA-positive strain being approximatively twice as potent as the VacA-negative strain; (2) addition of urea to the culture medium caused an approximatively 3-fold increase in the vacuolating activity of both urease-positive strains; (3) a VacA-negative/urease-negative strain did not exert any vacuolating effect, either in the presence or in the absence of urea; (4) the ratio between cell vacuolation induced by VacA-positive and VacA-negative strains was enhanced by the presence of AHA: ratio was about 2 in the absence of AHA and about 6 in the presence of AHA, either with or without urea added. The increment of vacuolation is likely due to an interaction between AHA and VacA. In conclusion, a VacA-negative/urease-positive strain becomes highly cytotoxic when physiological levels of urea are present in the incubation medium. This finding suggests that all urease-positive H. pylori strains, both with and without VacA expression, should be considered as potentially cytotoxic for the human gastric mucosa, although VacA enhances the severity of cell damage.

show abstract

Section: Discussionmentioning

confidence: 83%

Significance of Ammonia in the Genesis of Gastric Epithelial Lesions Induced by <i>Helicobacter pylori:</i> An in vitro Study with Different Bacterial Strains and Urea Concentrations

Sommi

Ricci²,

Fiocca

et al. 1996

Digestion

View full text Add to dashboard Cite

show abstract

“…Although there is no report about higher level of urease activity in patients with peptic ulcer, the increased activity was previously established in strains from cancer patients (Ito et al, 1995). In a study by Xu et al (1990) it was shown that urease inhibitor can cause a 75% drop in vacuolating gastric cells that had been induced by defined concentration of urease. While our results showed higher activity of this enzyme in the strains collected from ulcerative tissue, it remains to clarify its effect on gastric acid secretion and ulcer formation in these patients.…”

Section: Discussionmentioning

confidence: 99%

Relationship between ureB Sequence Diversity, Urease Activity and Genotypic Variations of Different Helicobacter pylori Strains in Patients with Gastric Disorders

Ghalehnoei

Ahmadzadeh

Farzi

et al. 2016

Polish Journal of Microbiology

View full text Add to dashboard Cite

A b s t r a c tAssociation of the severity of Helicobacter pylori induced diseases with virulence entity of the colonized strains was proven in some studies. Urease has been demonstrated as a potent virulence factor for H. pylori. The main aim of this study was investigation of the relationships of ureB sequence diversity, urease activity and virulence genotypes of different H. pylori strains with histopathological changes of gastric tissue in infected patients suffering from different gastric disorders. Analysis of the virulence genotypes in the isolated strains indicated significant associations between the presence of severe active gastritis and cagA + (P = 0.039) or cagA/iceA1 genotypes (P = 0.026), and intestinal metaplasia and vacA m1 (P = 0.008) or vacA s1/m2 (P = 0.001) genotypes. Our results showed a 2.4-fold increased risk of peptic ulcer (95% CI: 0.483-11.93), compared with gastritis, in the infected patients who had dupA positive strains; however this association was not statistically significant. The results of urease activity showed a significant mean difference between the isolated strains from patients with PUD and NUD (P = 0.034). This activity was relatively higher among patients with intestinal metaplasia. Also a significant association was found between the lack of cagA and increased urease activity among the isolated strains (P = 0.036). While the greatest sequence variation of ureB was detected in a strain from a patient with intestinal metaplasia, the sole determined amino acid change in UreB sequence (Ala201Thr, 30%), showed no influence on urease activity. In conclusion, the supposed role of H. pylori urease to form peptic ulcer and advancing of intestinal metaplasia was postulated in this study. Higher urease activity in the colonizing H. pylori strains that present specific virulence factors was indicated as a risk factor for promotion of histopathological changes of gastric tissue that advance gastric malignancy. K e y w o r d s: Helicobacter pylori, virulence, factor urease activity, histopathological changes

show abstract

“…In addition to pathogenicity from H. pylori, evidence indicates that ammonia generated by urease can cause injury to the gastroduodenal mucosa (33,42). Specific inhibition of urease activity has been proposed as a possible strategy to inhibit this microorganism (25).…”

mentioning

confidence: 99%

Inhibition ofHelicobacter pyloriand Associated Urease by Oregano and Cranberry Phytochemical Synergies

Lin

Kwon

Labbé

et al. 2005

Appl Environ Microbiol

141

View full text Add to dashboard Cite

Ulcer-associated dyspepsia is caused by infection with Helicobacter pylori. H. pylori is linked to a majority of peptic ulcers. Antibiotic treatment does not always inhibit or kill H. pylori with potential for antibiotic resistance. The objective of this study was to determine the potential for using phenolic phytochemical extracts to inhibit H. pylori in a laboratory medium. Our approach involved the development of a specific phenolic profile with optimization of different ratios of extract mixtures from oregano and cranberry. Subsequently, antimicrobial activity and antimicrobial-linked urease inhibition ability were evaluated. The results indicated that the antimicrobial activity was greater in extract mixtures than in individual extracts of each species. The results also indicate that the synergistic contribution of oregano and cranberry phenolics may be more important for inhibition than any species-specific phenolic concentration. Further, based on plate assay, the likely mode of action may be through urease inhibition and disruption of energy production by inhibition of proline dehydrogenase at the plasma membrane.Dyspepsia and related problems with peptic ulcers linked to Helicobacter pylori are major problems in many parts of the world (37). H. pylori is a gram-negative, spiral-shaped bacterium that lives in the stomach and duodenum. By releasing an enzyme called "urease," H. pylori is able to survive in the stomach. Urease converts urea into ammonia, which then counters the stomach acid. This creates a neutralizing environment for protecting H. pylori from the acid in the stomach. Gastric infection with H. pylori may lead to the onset of various gastric-related diseases (13). Most patients specifically with duodenal ulcer can be cured by killing H. pylori with antibiotics and proton pump inhibitors (22, 29). In recent studies, H. pylori infection was also suspected to be associated with coronary artery and ischemic heart disease (4, 9, 21, 23). Many antibiotic-linked treatments have been recommended for eradication of H. pylori, but the emergence of antibiotic resistance makes the treatments more complicated, and the infection is sustained at higher levels when the drug treatment is stopped (12,29). Two common antibiotics used for treatment of H. pylori infection are metronidazole and clarithromycin. Several triple-or quadruple-antibiotic therapies with proton pump inhibitors have been shown to be effective in eradication of H. pylori (14), but no single treatment regimen is considered the final treatment of choice.Research has indicated that urease of H. pylori is located in the cytoplasm in freshly prepared cultures and in the outer membrane in older cultures (15). In addition to pathogenicity from H. pylori, evidence indicates that ammonia generated by urease can cause injury to the gastroduodenal mucosa (33, 42). Specific inhibition of urease activity has been proposed as a possible strategy to inhibit this microorganism (25). It has been demonstrated that a urease-negative mutant does not cause ga...

show abstract

Intracellular Vacuolization Caused by the Urease of Helicobacter pylori

Cited by 67 publications

References 10 publications

Significance of Ammonia in the Genesis of Gastric Epithelial Lesions Induced by <i>Helicobacter pylori:</i> An in vitro Study with Different Bacterial Strains and Urea Concentrations

Significance of Ammonia in the Genesis of Gastric Epithelial Lesions Induced by <i>Helicobacter pylori:</i> An in vitro Study with Different Bacterial Strains and Urea Concentrations

Relationship between ureB Sequence Diversity, Urease Activity and Genotypic Variations of Different Helicobacter pylori Strains in Patients with Gastric Disorders

Inhibition ofHelicobacter pyloriand Associated Urease by Oregano and Cranberry Phytochemical Synergies

Contact Info

Product

Resources

About