Bismuth-mediated disruption of the glycocalyx- cell wall of Helicobacter pylori:ultrastructural evidence for a mechanism of action for bismuth salts

Stratton, Charles W.; Warner, R.R.; Coudron, P E; Lilly, North A.

doi:10.1093/jac/43.5.659

Cited by 38 publications

(26 citation statements)

References 36 publications

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“…However, our hypothesis that the antimicrobial action of bismuth was due to the inhibition of iron uptake was challenged by unchanged intracellular iron levels in two of the three H. pylori strains following culturing in the presence of this bismuth compound. Bismuth-induced changes in H. pylori morphology have been seen before (11,45,47), but our observations of accompanying changes in outer membrane protein and LPS profiles are new. The bismuth-induced changes included the up-regulation of a 12-kDa protein and two proteases and diminished LPS expression and are identical to those observed in other studies in which H. pylori was grown under iron-limiting conditions (9,29).…”

Section: Discussionmentioning

confidence: 53%

The Action of Bismuth against Helicobacter pylori Mimics but Is Not Caused by Intracellular Iron Deprivation

Bland

Ismail

Heinemann

et al. 2004

Antimicrob Agents Chemother

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Helicobacter pylori is highly susceptible to bismuth, a heavy metal with antimicrobial activity linked to its effect on bacterial iron uptake. Three strains of H. pylori were analyzed for indicators of iron limitation following exposure to the MIC of colloidal bismuth subcitrate (MIC CBS ). Similar morphologic and outer membrane changes were observed following growth in iron-limiting medium and at the MIC CBS that inhibited the growth of all three strains. These changes, which were also observed for iron-limited bacteria, were alleviated by the addition of iron to the cultures. H. pylori ATP levels, reduced in iron-limiting medium, were below the limits of detection in two of the three strains following exposure to bismuth. The addition of iron partially restored bacterial ATP levels in these two strains, although not to normal concentrations. In contrast, exposure of the same strains to the MIC CBS failed to deplete intracellular levels of iron, which were significantly reduced by culturing in iron-limiting medium. Thus, the antimicrobial effect of bismuth and of iron limitation on H. pylori may be similar. However, the respective mechanisms of intracellular action would appear to be mediated by different pathways within the cell.Prior to the discovery of the link between Helicobacter pylori and peptic ulcer disease (10), ulcers were thought to result from abnormal levels of gastric acid secretion. Bismuth compounds, commonly prescribed for ulcers, were initially thought to act as a barrier to the digestive effects of stomach acid by coating the ulcer site (31). Instead, it appears that H. pylori is highly susceptible to bismuth compounds (39), and treatment with colloidal bismuth subcitrate (CBS) is associated with a reduction in bacterial numbers and a concurrent reduction in gastritis in vivo (37). Despite these findings, bismuth monotherapy often fails to completely eradicate these bacteria (13,43), an observation that correlates with increasing ulcer relapse rates over time (34).The oldest regimen, an extremely effective one for clearing H. pylori infection, uses bismuth in combination with certain antibiotics (2, 51). Bismuth "triple therapy" consists of a bismuth compound (usually CBS or bismuth subsalicylate) in combination with metronidazole and tetracycline or amoxicillin (16) and reportedly cures 87.9% of patients within 1 week of treatment and 89.2% of patients within 2 weeks of treatment (49). H. pylori strains resistant to bismuth have not been reported and presumably arise at a lower frequency than strains resistant to antimicrobial agents such as nitroimidazoles, macrolides, and tetracycline (40). Bismuth compounds may reduce the development of resistance to coadministered antibiotics (27) and are also effective at treating H. pylori strains with established resistance to other antibiotics (3, 40). How bismuth is toxic to H. pylori is not known. A number of studies have linked the antimicrobial activities of many heavy metals, including bismuth, to their effects on iron uptake by bacteria (1,21,...

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Section: Discussionmentioning

confidence: 53%

The Action of Bismuth against Helicobacter pylori Mimics but Is Not Caused by Intracellular Iron Deprivation

Bland

Ismail

Heinemann

et al. 2004

Antimicrob Agents Chemother

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“…Furthermore, it possess antibacterial effects by inhibiting various enzymes produced by H. py Data are presented as n (%) with 95% CI. See Table 1 lori (including urease, catalase, and lipase/phospholipase), preventing adhesion of H. pylori to surface epithelial cells, and inhibiting ATP synthesis and some membrane functions in H. pylori [20][21][22]. It has been reported that the addition of bismuth to standard triple therapy improved the eradication rate [23,24].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Helicobacter pylori Eradication Rates of 2-Week Levofloxacin-Containing Triple Therapy, Levofloxacin-Containing Bismuth Quadruple Therapy, and Standard Bismuth Quadruple Therapy as a First-Line Regimen

et al. 2017

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i.d, levofloxacin 500 mg, once daily). The primary outcome was the eradication rate in the intention-to-treat (ITT) and per protocol (PP) analysis. Results: The eradication rates of the above 3 groups using ITT analysis were RBAL 83.8%, RBMT 88.3%, and RAL 74.8% compared with 91.2, 92.5, and 79.2%, respectively, using PP analysis. The eradication rate using RBMT was significantly higher than that of RAL (p = 0.029 in ITT analysis and p = 0.017 in PP analysis). Several side effects occurred in 156 patients (54.1%) KeywordsHelicobacter pylori infection · Bismuth-containing quadruple therapy · Levofloxacin-containing triple therapy · Eradication rate Abstract Objective: The aim of this study was to compare the efficacy and safety of 2-week levofloxacin-containing triple therapy, levofloxacin-containing bismuth quadruple therapy, and standard bismuth-containing quadruple therapy as a firstline regimen for the eradication of Helicobacter pylori. Methods: A total of 329 patients with H. pylori infection were randomly divided into 3 groups to receive one of the following regimens: (a) levofloxacin-containing bismuth quadruple Significance of the Study• This study compared the efficacy of 3 Helicobacter pylori eradication regimens, 2 of which contained levofloxacin, as the first line of treatment. Both quadruple regimens (standard bismuth quadruple therapy or levofloxacin-containing bismuth quadruple therapy) were highly effective in eradicating the infection and significantly superior to levofloxacin-containing triple therapy. Quadruple therapies should be used as first-line therapy for H. pylori infection.

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“…Manhar18 reported that Bi 3+ possesses antimicrobial activity against a wide range of bacteria, particularly Helicobacter pylori. When exposed to bismuth salts H. pylori cells become swollen and distorted and exhibit membrane–cell wall blebbing 31, 32. Therefore, it seems reasonable to employ bismuth as an antimicrobial component in pulp‐capping cement.…”

Section: Discussionmentioning

confidence: 99%

An in vitro investigation of the mechanical–chemical and biological properties of calcium phosphate/calcium silicate/bismutite cement for dental pulp capping

Shen

Sun

et al. 2010

J Biomed Mater Res

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The properties of new calcium phosphate/calcium silicate/bismutite (CPCSBi) cement were compared with those of calcium hydroxide (CH) and Dycal cements in dental pulp-capping applications. CPCSBi is composed of hydroxyapatite, tetracalcium phosphate, bismutite, and calcium silicate, which was analyzed by SEM, FTIR, and XRD. The results of ion release from CPCSBi showed that the concentrations of Bi(3+), Ca(2+), PO4(2-), and Si(4+) increased with time in deionized water solutions. The setting time of CPCSBi and Dycal was 13 min 50 s and 2 min 25 s, respectively. There were no statistical differences in compressive strength and solubility between CPCSBi and Dycal (p > 0.05). The pH of CPCSBi (10.9) was lower than that of CH (11.6) and Dycal (12.5) after immersion for 24 h. Only slight cytotoxicity appeared for CPCSBi, whereas both CH and Dycal produced moderate discoloration and lysis. In antimicrobial tests against Sm, Av, La, and Sa, the antimicrobial potency of the CPCSBi was approximately 5-10 times greater than that of Dycal and CH groups. The dissoluble dentin matrix components (DDMCs) extracted from CPCSBi exposed to dentin powder demonstrated increased expression of dentin sialophosphoprotein (DSPP) and soteocalcin (OCN) dramatically in human pulp cells by RT-PCR. These results suggest that CPCSBi will be a good candidate for use as a dental pulp-capping agent in future.

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Bismuth-mediated disruption of the glycocalyx- cell wall of Helicobacter pylori:ultrastructural evidence for a mechanism of action for bismuth salts

Cited by 38 publications

References 36 publications

The Action of Bismuth against Helicobacter pylori Mimics but Is Not Caused by Intracellular Iron Deprivation

The Action of Bismuth against Helicobacter pylori Mimics but Is Not Caused by Intracellular Iron Deprivation

Comparison of Helicobacter pylori Eradication Rates of 2-Week Levofloxacin-Containing Triple Therapy, Levofloxacin-Containing Bismuth Quadruple Therapy, and Standard Bismuth Quadruple Therapy as a First-Line Regimen

An in vitro investigation of the mechanical–chemical and biological properties of calcium phosphate/calcium silicate/bismutite cement for dental pulp capping

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