scholarly journals Furazolidone- and Nitrofurantoin-ResistantHelicobacter pylori: Prevalence and Role of Genes Involved in Metronidazole Resistance

2001 ◽  
Vol 45 (1) ◽  
pp. 306-308 ◽  
Author(s):  
Dong H. Kwon ◽  
Miae Lee ◽  
J. J. Kim ◽  
J. G. Kim ◽  
F. A. K. El-Zaatari ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Clinical Isolates ◽  
Metronidazole Resistance ◽  
H Pylori

ABSTRACT The prevalence of furazolidone, nitrofurantoin, and metronidazole resistance among Helicobacter pylori strains was assessed with 431 clinical isolates. Fifty-two percent were metronidazole resistant, compared to 2% (7 of 431) with resistance to furazolidone and nitrofurantoin. All seven furazolidone- and nitrofurantoin-resistant isolates were also metronidazole resistant.rdxA, frxA, and fdxB knockouts did not result in furazolidone or nitrofurantoin resistance. These data suggest that furazolidone and nitrofurantoin may be good alternatives to metronidazole for treating H. pylori infection.

scholarly journals Role of the rdxA and frxA genes in oxygen-dependent metronidazole resistance of Helicobacter pylori

2004 ◽  
Vol 53 (11) ◽  
pp. 1123-1128 ◽  
Author(s):  
Monique M Gerrits ◽  
Egbert-Jan van der Wouden ◽  
Dorine A Bax ◽  
Anton A van Zwet ◽  
Arnoud HM van Vliet ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Cell Viability ◽  
Protein Synthesis Inhibitor ◽  
Low Oxygen ◽  
Anaerobic Conditions ◽  
Metronidazole Resistance ◽  
Oxygen Conditions ◽  
H Pylori

Almost 50 % of all Helicobacter pylori isolates are resistant to metronidazole, which reduces the efficacy of metronidazole-containing regimens, but does not make them completely ineffective. This discrepancy between in vitro metronidazole resistance and treatment outcome may partially be explained by changes in oxygen pressure in the gastric environment, as metronidazole-resistant (MtzR) H. pylori isolates become metronidazole-susceptible (MtzS) under low oxygen conditions in vitro. In H. pylori the rdxA and frxA genes encode reductases which are required for the activation of metronidazole, and inactivation of these genes results in metronidazole resistance. Here the role of inactivating mutations in these genes on the reversibility of metronidazole resistance under low oxygen conditions is established. Clinical H. pylori isolates containing mutations resulting in a truncated RdxA and/or FrxA protein were selected and incubated under anaerobic conditions, and the effect of these conditions on the MICs of metronidazole, amoxycillin, clarithromycin and tetracycline, and cell viability were determined. While anaerobiosis had no effect on amoxycillin, clarithromycin and tetracycline resistance, all isolates lost their metronidazole resistance when cultured under anaerobic conditions. This loss of metronidazole resistance also occurred in the presence of the protein synthesis inhibitor chloramphenicol. Thus, factor(s) that activate metronidazole under low oxygen tension are not specifically induced by low oxygen conditions, but are already present under microaerophilic conditions. As there were no significant differences in cell viability between the clinical isolates, it is likely that neither the rdxA nor the frxA gene participates in the reversibility of metronidazole resistance.

scholarly journals Analysis of rdxA and Involvement of Additional Genes Encoding NAD(P)H Flavin Oxidoreductase (FrxA) and Ferredoxin-Like Protein (FdxB) in Metronidazole Resistance of Helicobacter pylori

2000 ◽  
Vol 44 (8) ◽  
pp. 2133-2142 ◽  
Author(s):  
Dong-Hyeon Kwon ◽  
Fouad A. K. El-Zaatari ◽  
Mototsugu Kato ◽  
Michael S. Osato ◽  
Rita Reddy ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Resistant Strain ◽  
Resistance Mechanisms ◽  
Sensitive Strain ◽  
Metronidazole Resistance ◽  
Genes Encoding ◽  
Resistant Strains ◽  
Flavin Oxidoreductase ◽  
H Pylori

ABSTRACT Metronidazole (Mtz) is a critical ingredient of modern multidrug therapies for Helicobacter pylori infection. Mtz resistance reduces the effectiveness of these combinations. Although null mutations in a rdxA gene that encodes oxygen-insensitive NAD(P)H nitroreductase was reported in Mtz-resistant H. pylori, an intact rdxA gene has also been reported in Mtz-resistant H. pylori, suggesting that additional Mtz resistance mechanisms exist in H. pylori. We explored the nature of Mtz resistance among 544 clinical H. pyloriisolates to clarify the role of rdxA inactivation in Mtz resistance and to identify another gene(s) responsible for Mtz resistance in H. pylori. Mtz resistance was present in 33% (181 of 544) of the clinical isolates. There was marked heterogeneity of resistance, with Mtz MICs ranging from 8 to ≥256 μg/ml.rdxA inactivation resulted in Mtz MICs of up to 32 μg/ml for 6 Mtz-sensitive H. pylori strains and 128 μg/ml for one Mtz-sensitive strain. Single or dual (with rdxA) inactivation of genes that encode ferredoxin-like protein (designatedfdxB) and NAD(P)H flavin oxidoreductase (frxA) also increased the MICs of Mtz for sensitive and resistant strains with low to moderate levels of Mtz resistance. fdxB inactivation resulted in a lower level of resistance than that from rdxAinactivation, whereas frxA inactivation resulted in MICs similar to those seen with rdxA inactivation. Further evidence for involvement of the frxA gene in Mtz resistance included the finding of a naturally inactivated frxA but an intact rdxA in an Mtz-resistant strain, complementation of Mtz sensitivity from an Mtz-sensitive strain to an Mtz-resistant strain or vice versa by use of naturally inactivated or functionalfrxA genes, respectively, and transformation of an Mtz-resistant Escherichia coli strain to an Mtz sensitive strain by a naturally functional frxA gene but not an inactivated frxA gene. These results are consistent with the hypothesis that null mutations in fdxB,frxA, or rdxA may be involved in Mtz resistance.

scholarly journals Proton motive force-dependent efflux of tetracycline in clinical isolates of Helicobacter pylori

2009 ◽  
Vol 58 (10) ◽  
pp. 1309-1313 ◽  
Author(s):  
Mona Anoushiravani ◽  
Tahereh Falsafi ◽  
Vahid Niknam
Keyword(s):  
Helicobacter Pylori ◽  
Proton Motive Force ◽  
Motive Force ◽  
Clinical Isolates ◽  
Carbonyl Cyanide ◽  
Agar Dilution ◽  
Resistant Mutants ◽  
H Pylori ◽  
High Level

The aim of this study was to evaluate the role of proton motive force (PMF)-dependent efflux in resistance of Helicobacter pylori to tetracycline (Tet). Tet MIC was determined by agar dilution in the presence and absence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), an inhibitor of PMF. Antibiotic accumulation was conducted in the presence or absence of CCCP and the fluorescence of the accumulated antibiotic was measured by spectrofluorometry. In the presence of CCCP, antibiotic accumulation was increased by 2–17-fold in 17/20 Tetr isolates and by 3–10-fold in four of five high-level-resistant mutants. Correlation was observed between this increase and diminution of MIC with CCCP. PMF-dependent efflux mechanisms therefore appear to play an important role in the resistance of clinical isolates of H. pylori to Tet.

scholarly journals Whole-Genome Sequencing and Comparative Genomics of Three Helicobacter pylori Strains Isolated from the Stomach of a Patient with Adenocarcinoma

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 331
Author(s):  
Montserrat Palau ◽  
Núria Piqué ◽  
M. José Ramírez-Lázaro ◽  
Sergio Lario ◽  
Xavier Calvet ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Virulence Factors ◽  
Outer Membrane Proteins ◽  
Whole Genome ◽  
Flagellar Biosynthesis ◽  
H Pylori ◽  
Restriction Modification

Helicobacter pylori is a common pathogen associated with several severe digestive diseases. Although multiple virulence factors have been described, it is still unclear the role of virulence factors on H. pylori pathogenesis and disease progression. Whole genome sequencing could help to find genetic markers of virulence strains. In this work, we analyzed three complete genomes from isolates obtained at the same point in time from a stomach of a patient with adenocarcinoma, using multiple available bioinformatics tools. The genome analysis of the strains B508A-S1, B508A-T2A and B508A-T4 revealed that they were cagA, babA and sabB/hopO negative. The differences among the three genomes were mainly related to outer membrane proteins, methylases, restriction modification systems and flagellar biosynthesis proteins. The strain B508A-T2A was the only one presenting the genotype vacA s1, and had the most distinct genome as it exhibited fewer shared genes, higher number of unique genes, and more polymorphisms were found in this genome. With all the accumulated information, no significant differences were found among the isolates regarding virulence and origin of the isolates. Nevertheless, some B508A-T2A genome characteristics could be linked to the pathogenicity of H. pylori.

scholarly journals Systems Modeling of the Role of Interleukin-21 in the Maintenance of Effector CD4+ T Cell Responses during Chronic Helicobacter pylori Infection

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Adria Carbo ◽  
Danyvid Olivares-Villagómez ◽  
Raquel Hontecillas ◽  
Josep Bassaganya-Riera ◽  
Rupesh Chaturvedi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
T Cell ◽  
Wild Type ◽  
Content Type ◽  
Interleukin 21 ◽  
H Pylori ◽  
Deficient Mice

ABSTRACTThe development of gastritis duringHelicobacter pyloriinfection is dependent on an activated adaptive immune response orchestrated by T helper (Th) cells. However, the relative contributions of the Th1 and Th17 subsets to gastritis and control of infection are still under investigation. To investigate the role of interleukin-21 (IL-21) in the gastric mucosa duringH. pyloriinfection, we combined mathematical modeling of CD4+T cell differentiation within vivomechanistic studies. We infected IL-21-deficient and wild-type mice withH. pyloristrain SS1 and assessed colonization, gastric inflammation, cellular infiltration, and cytokine profiles. ChronicallyH. pylori-infected IL-21-deficient mice had higherH. pyloricolonization, significantly less gastritis, and reduced expression of proinflammatory cytokines and chemokines compared to these parameters in infected wild-type littermates. Thesein vivodata were used to calibrate anH. pyloriinfection-dependent, CD4+T cell-specific computational model, which then described the mechanism by which IL-21 activates the production of interferon gamma (IFN-γ) and IL-17 during chronicH. pyloriinfection. The model predicted activated expression of T-bet and RORγt and the phosphorylation of STAT3 and STAT1 and suggested a potential role of IL-21 in the modulation of IL-10. Driven by our modeling-derived predictions, we found reduced levels of CD4+splenocyte-specifictbx21androrcexpression, reduced phosphorylation of STAT1 and STAT3, and an increase in CD4+T cell-specific IL-10 expression inH. pylori-infected IL-21-deficient mice. Our results indicate that IL-21 regulates Th1 and Th17 effector responses during chronicH. pyloriinfection in a STAT1- and STAT3-dependent manner, therefore playing a major role controllingH. pyloriinfection and gastritis.IMPORTANCEHelicobacter pyloriis the dominant member of the gastric microbiota in more than 50% of the world’s population.H. pyloricolonization has been implicated in gastritis and gastric cancer, as infection withH. pyloriis the single most common risk factor for gastric cancer. Current data suggest that, in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonization and chronic infection. This study uses a combined computational and experimental approach to investigate how IL-21, a proinflammatory T cell-derived cytokine, maintains the chronic proinflammatory T cell immune response driving chronic gastritis duringH. pyloriinfection. This research will also provide insight into a myriad of other infectious and immune disorders in which IL-21 is increasingly recognized to play a central role. The use of IL-21-related therapies may provide treatment options for individuals chronically colonized withH. pylorias an alternative to aggressive antibiotics.

Frequency of rdx A Deletion Mutation Conferring Metronidazole Resistance in Helicobacter pylori

2020 ◽  
Vol 29 (3) ◽  
pp. 59-64
Author(s):  
Hanaa M. El Maghraby ◽  
Samar Mohaseb
Keyword(s):  
Helicobacter Pylori ◽  
Epigastric Pain ◽  
Deletion Mutation ◽  
Rapid Urease Test ◽  
Rrna Gene ◽  
University Hospitals ◽  
Metronidazole Resistance ◽  
Urease Test ◽  
Gastric Biopsies ◽  
H Pylori

Background: Metronidazole is one of the antimicrobial drugs that can be used in combination with other drugs for eradication of Helicobacter pylori (H. pylori).Unfortunately, metronidazole resistance in H. plori is an increasing health problem which may be attributed to inactivation of many genes as rdx A gene. Objective: To determine the frequency of rdx A deletion mutation in H. pylori detected in infected patients attending at the Gastroenterology Unit, Zagazig University Hospitals. Methodology: Two gastric biopsies were taken from each enrolled patient by endoscopy. H.pylori detection was done by rapid urease test and polymerase chain reaction (PCR) amplification of 16S rRNA gene. Deletion mutation in rdx A gene was detected by conventional PCR. Results: Out of 134 doubled gastric biopsies obtained from 134 patients, 52.2% were positive for H. pylori. Epigastric pain, vomiting and gastritis were significantly associated with detection of H. pylori infection (p˂ 0.05). Deletion mutation of rdx A gene was detected in 28.6% of H. pylori positive specimens obtained from infected patients. Conclusion: Deletion mutation of rdx A gene is a frequent determinant of rdx A inactivation conferring metronidazole resistance among H. pylori.

E-Test or Agar Dilution for Metronidazole Susceptibility Testing of Helicobacter Pylori: Importance of the Prevalence of Metronidazole Resistance

2021 ◽  
Author(s):  
Jinnan Chen ◽  
Yu Huang ◽  
Zhaohui Ding ◽  
Xiao Liang ◽  
Hong Lu
Keyword(s):  
Helicobacter Pylori ◽  
Susceptibility Testing ◽  
Resistance Rate ◽  
Test Method ◽  
Major Error ◽  
Metronidazole Resistance ◽  
Agar Dilution ◽  
H Pylori ◽  
High Level ◽  
Level Resistance

Abstract Background: A number of studies have shown that E-test overestimated the presence of Helicobacter pylori (H. pylori) resistance compared to agar dilution.Objective: The purpose of this study was to explore whether E-test could be an alternative for agar dilution to detect the metronidazole susceptibility of H. pylori.Method: E-test and agar dilution were used to assess susceptibility of H. pylori to metronidazole, clarithromycin and levofloxacin in 281 clinical isolates obtained from China where resistance was high. Cohen kappa analysis, McNemar test, essential and categorical agreement analysis were performed for these two methods. Results: Overall, the result of E-test showed similar prevalence of resistance rate to all antibiotics compared with agar dilution. The essential agreement (EA) of E-test method and agar dilution in the evaluation susceptibility of H. pylori to clarithromycin and levofloxacin were moderate, with 89.0% and 79.7% respectively, but only 45.9% for metronidazole. Results showed categorical agreement (CA) between E-test and agar dilution were 100% for both clarithromycin and levofloxacin. As for metronidazole, the CA was 98.7%, no major error was identified, and rate of very major error was 1.8%.Conclusion: E-test can be an alternative method to detect the metronidazole susceptibility of H. pylori in regions where high-level resistance is common.

scholarly journals Genotyping pattern of the vacuolating cytotoxin A and cytotoxin associated gene A of the Helicobacter pylori strains detected in fecal samples of household dogs

2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Asieh Bolandi ◽  
Saam Torkan ◽  
Iman Alavi
Keyword(s):  
Helicobacter Pylori ◽  
16S Rrna ◽  
16S Rrna Gene ◽  
Pcr Amplification ◽  
Rrna Gene ◽  
Fecal Samples ◽  
The Status ◽  
Cytotoxin Associated Gene A ◽  
H Pylori

In despite of the high clinical impact of Helicobacter pylori, its exact sources and routes of transmission are unknown. Dogs may play an imperative role in the transmission of H. pylori to humans. The current investigation was done to study the status of vacA and cagA genotypes in the H. pylori strains of dogs. One-hundred and fifty fecal samples were collected from healthy and complicated household dogs. Genomic DNA was extracted from fecal samples and presence of 16S rRNA gene was studied using the PCR amplification. Distribution of vacA and cagA genotypes were studied by the multiplex PCR. Thirteen out of 150 fecal samples (8.66%) were positive for H. pylori 16S rRNA gene. Prevalence of H. pylori in healthy and complicated dogs were 5.55% and 8.57%, respectively. Male had the higher prevalence of H. pylori (P=0.038). The most commonly detected genotypes among the H. pylori strains were vacAs1A (61.53%), cagA (38.46%), vacAm1a (38.46%), vacAs2 (30.76%) and vacAm2 (30.76%). The most commonly detected combined genotypes were s1aCagA (30.76%), s1am1a (23.07%), s2m1a (23.07%) and s2CagA (23.07%). Iranian household dogs harbor H. pylori in their fecal samples similar in genotypes of the vacA and cagA alleles which suggest that complicated and even healthy dogs may be the latent host of the H. pylori and its genotypes. However, supplementary studies are required to found the exact role of dogs as a definitive host of the H. pylori.

scholarly journals Effect of Helicobacter pylori on Polymorphonuclear Leukocyte Migration across Polarized T84 Epithelial Cell Monolayers: Role of Vacuolating Toxin VacA and cagPathogenicity Island

2000 ◽  
Vol 68 (9) ◽  
pp. 5225-5233 ◽  
Author(s):  
Véronique Hofman ◽  
Vittorio Ricci ◽  
Antoine Galmiche ◽  
Patrick Brest ◽  
Patrick Auberger ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Polymorphonuclear Leukocyte ◽  
Broth Culture ◽  
Intestinal Cell ◽  
T84 Cells ◽  
Vacuolating Cytotoxin ◽  
Intestinal Cell Line ◽  
H Pylori

ABSTRACT Helicobacter pylori infection can induce polymorphonuclear leukocyte (PMNL) infiltration of the gastric mucosa, which characterizes acute chronic gastritis. The mechanisms underlying this process are poorly documented. The lack of an in vitro model has considerably impaired the study of transepithelial migration of PMNL induced by H. pylori. In the present work, we used confluent polarized monolayers of the human intestinal cell line T84 grown on permeable filters to analyze the epithelial PMNL response induced by broth culture filtrates (BCFs) and bacterial suspensions from different strains of H. pylori. We have evaluated the role of the vacuolating cytotoxin VacA and of the cagpathogenicity island (PAI) of H. pylori in PMNL migration via their effects on T84 epithelial cells. We noted no difference in the rates of PMNL transepithelial migration after epithelial preincubation with bacterial suspensions or with BCFs of VacA-negative or VacA-positive H. pylori strains. In contrast, PMNL transepithelial migration was induced after incubation of the T84 cells with cag PAI-positive and cagE-positiveH. pylori strains. Finally, PMNL migration was correlated with a basolateral secretion of interleukin-8 by T84 cells, thus creating a subepithelial chemotactic gradient for PMNL. These data provide evidence that the vacuolating cytotoxin VacA is not involved in PMNL transepithelial migration and that the cag PAI, with a pivotal role for the cagE gene, provokes a transcellular signal across T84 monolayers, inducing a subepithelial PMNL response.

scholarly journals Antibiotic Resistance Prevalence and Trends in Patients Infected with Helicobacter pylori in the Period 2013–2020: Results of the European Registry on H. pylori Management (Hp-EuReg)

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1058
Author(s):  
Luis Bujanda ◽  
Olga P. Nyssen ◽  
Dino Vaira ◽  
Ilaria M. Saracino ◽  
Giulia Fiorini ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Antimicrobial Susceptibility ◽  
Susceptibility Testing ◽  
Resistance Rate ◽  
Antimicrobial Susceptibility Testing ◽  
Metronidazole Resistance ◽  
Infected Adult ◽  
H Pylori ◽  
European Registry

Background: Bacterial antibiotic resistance changes over time depending on multiple factors; therefore, it is essential to monitor the susceptibility trends to reduce the resistance impact on the effectiveness of various treatments. Objective: To conduct a time-trend analysis of Helicobacter pylori resistance to antibiotics in Europe. Methods: The international prospective European Registry on Helicobacter pylori Management (Hp-EuReg) collected data on all infected adult patients diagnosed with culture and antimicrobial susceptibility testing positive results that were registered at AEG-REDCap e-CRF until December 2020. Results: Overall, 41,562 patients were included in the Hp-EuReg. Culture and antimicrobial susceptibility testing were performed on gastric biopsies of 3974 (9.5%) patients, of whom 2852 (7%) were naive cases included for analysis. The number of positive cultures decreased by 35% from the period 2013–2016 to 2017–2020. Concerning naïve patients, no antibiotic resistance was found in 48% of the cases. The most frequent resistances were reported against metronidazole (30%), clarithromycin (25%), and levofloxacin (20%), whereas resistances to tetracycline and amoxicillin were below 1%. Dual and triple resistances were found in 13% and 6% of the cases, respectively. A decrease (p < 0.001) in the metronidazole resistance rate was observed between the 2013–2016 (33%) and 2017–2020 (24%) periods. Conclusion: Culture and antimicrobial susceptibility testing for Helicobacter pylori are scarcely performed (<10%) in Europe. In naïve patients, Helicobacter pylori resistance to clarithromycin remained above 15% throughout the period 2013–2020 and resistance to levofloxacin, as well as dual or triple resistances, were high. A progressive decrease in metronidazole resistance was observed.

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