Cytopathic effects of Campylobacter pylori urease.

Barer, Michael R.; Elliott, T. S. J.; Berkeley, D; Thomas, J. Earl; Eastham, E J

doi:10.1136/jcp.41.5.597-a

Cited by 56 publications

(22 citation statements)

References 4 publications

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“…Furthermore, ammonia liberated by urease is known to cause cell injury and to induce cell vacuolation [41][42][43][44]. Therefore, examination of urease production levels in H. pylori cultures treated with drugs might be valuable for investigation of therapeutic agents for H. pylori infection.…”

Section: Discussionmentioning

confidence: 99%

Nitazoxanide, a Nitrothiazolide Antiparasitic Drug, Is an Anti-<i>Helicobacter pylori</i> Agent with Anti-Vacuolating Toxin Activity

et al. 1999

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Nitazoxanide (NTZ), a synthesized drug of the nitrothiazolide class, was initially developed as an antiparasitic compound. This compound has recently been shown to have antibacterial activities against some bacterial pathogens. In the present study, NTZ and its main metabolite tizoxanide (TIZ) were found to have strong minimum inhibitory concentrations (MICs) against both metronidazole (MTZ)-resistant strains and sensitive clinical isolates of Helicobacter pylori. The MIC₉₀ of both NTZ and TIZ against 37 clinical isolates was 8 μg/ml. Vacuolating toxin activity of H. pylori assayed by HeLa cell vacuole formation was inhibited by NTZ at a sub-MIC. In contrast, urease production by H. pylori was not specifically affected by the sub-MIC of NTZ. An acidic pH (pH 5.0) medium reduced the antimicrobial activity of the drug in terms of growth inhibition due to the low growth rate of the bacteria, but killing activity of NTZ against the bacteria was still observed. Thus, it was apparent that both NTZ and TIZ are highly effective against H. pylori, even when the bacteria are resistant to MTZ.

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Section: Discussionmentioning

confidence: 99%

Nitazoxanide, a Nitrothiazolide Antiparasitic Drug, Is an Anti-<i>Helicobacter pylori</i> Agent with Anti-Vacuolating Toxin Activity

et al. 1999

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“…Ammonia generated by the hydrolysis of urea neutralizes gastric acidity and forms a neutral microenvironment surrounding the bacterium within the gastric lumen. However, some evidence has shown that ammonia can cause local injury to gastroduodenal mucus tissue (Barer et al, 1986;Hazell et al, 1986;Smoot et al, 1990;Buck et al, 1990). Although infection by H. pylori is treated by using antibiotics (Goodwin et al, 1986;Nagata et al, 1993), the complete abolition of the infection became difficult with the advent of a resistant bacterium.…”

Section: Introductionmentioning

confidence: 97%

Recombinant antigen from Helicobacter pylori urease as vaccine against H. pylori‐associated disease

Fujii¹,

Morihara²,

Fukushima

et al. 2004

Biotech & Bioengineering

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It is well documented that the enzymatic active site of Helicobacter pylori urease is present in the beta-subunit. An important sequence of 135 amino acids of the beta-subunit was determined from the structure of H. pylori urease and by a homology-based study of the urease of other bacteria and plants. The sequence (UreB) was expressed in Escherichia coli as a recombinant fusion protein with glutathione-S-transferase (GST). Seventeen monoclonal antibodies, UA-1-17, were produced using the UreB-GST as the immunogen. The obtained monoclonal antibodies showed a high specificity to UreB, and some of the MAbs cross-reacted with Jack bean urease. About 70% of the established MAbs displayed an inhibitory effect on the enzymatic activity of the urease. Among them, UA-15 MAb could reduce the activity by 53% and it immunologically binds to the bacterium infecting the human stomach mucosa. The antiserum induced by immunization with a recombinant UreB-GST into rabbits displayed a specific binding to mucosal surfaces of the human stomach infected with the pathogen H. pylori. Moreover, the antiserum suppressed the enzymatic activity of H. pylori urease, while the purified H. pylori urease could not induce such an antiserum.

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“…Ammonia, a principal nitrogenous excretory product of parasites (Barrett 1981), is cytotoxic and inhibits acid secretion in dispersed rabbit gastric glands (Fryklund et al 1990;Hagen et al 1997;Merkelbach et al 2002) and in amphibian gastric mucosa (Hagen et al 2000). The weak base also reduces proliferation of cells in culture (Hassell et al 1991;Schneider et al 1996) and induces cell damage (Barer et al 1988;Smoot et al 1990) and cell vacuolation (De Duve et al 1974;Ohkuma and Poole 1981;Xu et al 1990;Cover et al 1991). To exclude this possible effect of ammonia on HeLa cells, a negative control containing 8-mM NH 4 Cl was carried out.…”

Section: Discussionmentioning

confidence: 94%

Effects of excretory/secretory products of Haemonchus contortus on cell vacuolation

et al. 2005

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Excretory/secretory (ES) products of the gastric nematode, Haemonchus contortus, have been implicated in the inhibition of gastric acid secretion which follows infection. Parietal cell vacuolation has been observed in abomasal sections from parasitised sheep, and ES prepared in vitro has been reported to cause vacuolation and to increase neutral red (NR) uptake in epithelial cell cultures. We have used the latter approach to examine, at the cellular level, the effects of ES prepared from L3 and adult nematodes. Both NR uptake and cellular vacuolation were increased following exposure to larval or adult ES products. ES preparations from adult worms induced more extensive vacuolation then those from L3 worms and, as with VacA treatment, adherent cells remained viable despite high levels of vacuolation. Whereas VacA-induced vacuolation resulted in NR uptake predominantly localised in vacuoles, this appeared not to be the case with ES-induced vacuolation, suggesting that different mechanisms might be involved. Both ES and VacA exposure was associated with an increased rate of cell detachment.

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Cytopathic effects of Campylobacter pylori urease.

Cited by 56 publications

References 4 publications

Nitazoxanide, a Nitrothiazolide Antiparasitic Drug, Is an Anti-<i>Helicobacter pylori</i> Agent with Anti-Vacuolating Toxin Activity

Nitazoxanide, a Nitrothiazolide Antiparasitic Drug, Is an Anti-<i>Helicobacter pylori</i> Agent with Anti-Vacuolating Toxin Activity

Recombinant antigen from Helicobacter pylori urease as vaccine against H. pylori‐associated disease

Effects of excretory/secretory products of Haemonchus contortus on cell vacuolation

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