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

2004 ◽  
Vol 48 (6) ◽  
pp. 1983-1988 ◽  
Author(s):  
Michael V. Bland ◽  
Salim Ismail ◽  
Jack A. Heinemann ◽  
Jacqueline I. Keenan
Keyword(s):  
Helicobacter Pylori ◽  
Antimicrobial Effect ◽  
Iron Limitation ◽  
Intracellular Iron ◽  
Colloidal Bismuth Subcitrate ◽  
Iron Deprivation ◽  
Atp Levels ◽  
Bismuth Subcitrate ◽  
Membrane Changes ◽  
H Pylori

ABSTRACT 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 (MICCBS). Similar morphologic and outer membrane changes were observed following growth in iron-limiting medium and at the MICCBS 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 MICCBS 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.

scholarly journals Influence of metronidazole resistance on efficacy of quadruple therapy for Helicobacter pylori eradication

Gut ◽  
1998 ◽  
Vol 42 (2) ◽  
pp. 166-169 ◽  
Author(s):  
R W M van der Hulst ◽  
A van der Ende ◽  
A Homan ◽  
P Roorda ◽  
J Dankert ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Triple Therapy ◽  
Quadruple Therapy ◽  
Colloidal Bismuth Subcitrate ◽  
Intention To Treat ◽  
Group I ◽  
Bismuth Subcitrate ◽  
Metronidazole Resistance ◽  
Group Ii ◽  
H Pylori

Background—Metronidazole-containing eradication therapies are less effective for metronidazole resistantHelicobacter pylori. Although early data suggested improvement of the efficacy of bismuth triple therapy after the addition of acid suppressives, these findings were based on studies with small numbers of patients, incomplete post-eradication follow up, or omission of pretreatment susceptibility testing.Aims—To study the efficacy of quadruple therapy in the Amsterdam area, where the efficacy of bismuth triple therapy has been proved to be affected by metronidazole resistance.Patients and methods—Eighty two consecutive dyspeptic H pylori positive patients with either metronidazole susceptible (group I) or metronidazole resistant H pylori strains (group II) received quadruple therapy for one week: omeprazole 20 mg twice daily; colloidal bismuth subcitrate 120 mg four times a day; tetracycline 500 mg four times a day; metronidazole 500 mg three times a day. Susceptibility to metronidazole was determined by the E-test.Results—Intention to treat analysis showed thatH pylori infection had been cured in 42/43 patients (98%) in group I and 32/39 patients (82%) in group II (p = 0.02).Conclusion—The efficacy of quadruple therapy is significantly impaired in patients infected with metronidazole resistant H pylori. Therefore a non-metronidazole-containing regimen should preferably be used in areas known to have a high prevalence of pretreatment metronidazole resistance.

scholarly journals Small Molecule Inhibitors of the Response Regulator ArsR Exhibit Bactericidal Activity against Helicobacter pylori

2020 ◽  
Vol 8 (4) ◽  
pp. 503 ◽  
Author(s):  
Andrés González ◽  
Javier Casado ◽  
Eduardo Chueca ◽  
Sandra Salillas ◽  
Adrián Velázquez-Campoy ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
High Throughput Screening ◽  
Lithocholic Acid ◽  
Response Regulator ◽  
Bacterial Pathogen ◽  
Antimicrobial Effect ◽  
Chemical Library ◽  
Secondary Bile Acid ◽  
H Pylori

Helicobacter pylori is considered the most prevalent bacterial pathogen in humans. The increasing antibiotic resistance evolved by this microorganism has raised alarm bells worldwide due to the significant reduction in the eradication rates of traditional standard therapies. A major challenge in this antibiotic resistance crisis is the identification of novel microbial targets whose inhibitors can overcome the currently circulating resistome. In the present study, we have validated the use of the essential response regulator ArsR as a novel and promising therapeutic target against H. pylori infections. A high-throughput screening of a repurposing chemical library using a fluorescence-based thermal shift assay identified several ArsR binders. At least four of these low-molecular weight compounds noticeably inhibited the DNA binding activity of ArsR and showed bactericidal effects against antibiotic-resistant strains of H. pylori. Among the ArsR inhibitors, a human secondary bile acid, lithocholic acid, quickly destroyed H. pylori cells and exhibited partial synergistic action in combination with clarithromycin or levofloxacin, while the antimicrobial effect of this compound against representative members of the normal human microbiota such as Escherichia coli and Staphylococcus epidermidis appeared irrelevant. Our results enhance the battery of novel therapeutic tools against refractory infections caused by multidrug-resistant H. pylori strains.

scholarly journals Helicobacter pylori is killed by nitrite under acidic conditions

Gut ◽  
1998 ◽  
Vol 42 (3) ◽  
pp. 334-337 ◽  
Author(s):  
R S Dykhuizen ◽  
A Fraser ◽  
H McKenzie ◽  
M Golden ◽  
C Leifert ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Anaerobic Bacteria ◽  
Antimicrobial Effect ◽  
Human Stomach ◽  
Bacterial Survival ◽  
Novel Host ◽  
Potassium Nitrite ◽  
Acidic Conditions ◽  
H Pylori ◽  
Facultative Anaerobic Bacteria

Background—Due to the expression of urease,Helicobacter pylori is able to establish itself in the human stomach under acidic conditions. A novel host defence mechanism was recently proposed, suggesting that the formation of salivary nitrite in symbiosis with facultative anaerobic bacteria in the oropharynx, is aimed at enhancing the antimicrobial activity of gastric juice.Aims—To investigate whether the addition of nitrite in physiological concentrations influences the resistance ofH pylori to acid.Methods—H pylori cultured from fresh gastric biopsy specimens was exposed for 30 minutes to normal saline and to HCl/KCl buffer (0.2M) at pH 2 with urea (5 mM) added. The influence of potassium nitrite (50–1000 μmol/l) on bacterial survival was determined.Results—Addition of nitrite (1 mM) to acidic solutions (pH 2) resulted in complete kill of H pyloriwithin 30 minutes exposure time whereas acid alone allowed the organism to survive (p<0.001). The antimicrobial effect of nitrite at pH 2 against H pylori was dose dependent and complete kill of organisms occurred at concentrations ⩾500 μmol/l.Conclusion—Acidified nitrite has antibacterial activity against H pylori. This should prompt further research into the effect of salivary nitrite on the survival of H pylori in the human stomach.

Colloidal bismuth subcitrate and omeprazole inhibit alcohol dehydrogenase mediated acetaldehyde production by Helicobacter pylori

Life Sciences ◽  
1992 ◽  
Vol 51 (21) ◽  
pp. PL195-PL200 ◽  
Author(s):  
Risto P. Roine ◽  
Katja S. Salmela ◽  
Johanna Höök-Nikanne ◽  
Timo U. Kosunen ◽  
Mikko Salaspuro
Keyword(s):  
Helicobacter Pylori ◽  
Alcohol Dehydrogenase ◽  
Colloidal Bismuth Subcitrate ◽  
Bismuth Subcitrate ◽  
Acetaldehyde Production ◽  
Colloidal Bismuth

Three Treatment Schemes with Colloidal Bismuth Subcitrate (Q-ULCER) in Peptic Ulcer with Helicobacter pylori

1999 ◽  
Vol 30 (1) ◽  
pp. 55-59 ◽  
Author(s):  
Marcia Samada Suárez ◽  
Juan González Cansino ◽  
Cira Velasco Ilizalde ◽  
Carlos Alfonso Sabatier ◽  
Juan Castillo Hernández
Keyword(s):  
Helicobacter Pylori ◽  
Peptic Ulcer ◽  
Colloidal Bismuth Subcitrate ◽  
Bismuth Subcitrate ◽  
Colloidal Bismuth

scholarly journals Bismuth-Based Quadruple Therapy with Bismuth Subcitrate, Metronidazole, Tetracycline and Omeprazole in the Eradication ofHelicobacter pylori

2001 ◽  
Vol 15 (9) ◽  
pp. 581-585 ◽  
Author(s):  
Raymond Lahaie ◽  
Alain Farley ◽  
Chrystian Dallaire ◽  
André Archambault ◽  
Carlo A Fallone ◽  
...  
Keyword(s):  
Eradication Rate ◽  
Previous Attempt ◽  
Colloidal Bismuth Subcitrate ◽  
Minimal Inhibitory Concentrations ◽  
Bismuth Subcitrate ◽  
Antiulcer Drugs ◽  
Resistant Strains ◽  
H Pylori ◽  
Irritable Bowel ◽  
Intent To Treat

BACKGROUND: A previous study showed that 14 days of qid bismuth-based triple therapy with tetracycline 500 mg, metronidazole 250 mg and colloidal bismuth subcitrate 120 mg resulted in excellentHelicobacter pylorieradication rates (89.5%). The present study looked at a shorter treatment period by adding omeprazole and by reducing the dose of tetracycline.METHODS: One hundred sixty-one patients withH pyloriconfirmed by histology and13carbon urea breath test were included in the study. They were treated for seven days with bismuth subcitrate 120 mg plus metronidazole 250 mg plus tetracycline 250 mg qid plus omeprazole 20 mg bid (OBMT). Patients were 18 to 75 years of age and had dyspepsia with or without a history of peptic ulcer. Patients with irritable bowel syndrome, active ulcer or previous attempt at eradication, or those who had used antibiotics or antiulcer drugs in the previous 30 days were excluded. Eradication was determined by two13carbon urea breath tests done one and three months, respectively, after treatment. Strains with minimal inhibitory concentrations of 8 µg/mL or higher were considered to be resistant to metronidazole.RESULTS: The overall per protocol eradication rate was 84% - 89.5% in metronidazole-sensitive and 70.8% in metronidazole-resistant strains. Modified intent-to-treat analysis resulted in a 80% eradication rate - 82.5% in metronidazole-sensitive and 66.7% in metronidazole-resistant strains. Only one patient discontinued treatment because of adverse events.CONCLUSIONS: The OBMT regimen used in this study is safe and effective against metronidazole-sensitiveH pyloristrains.

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