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Valenzuela-Hormazabal P, Sepúlveda RV, Alegría-Arcos M, Valdés-Muñoz E, Rojas-Pérez V, González-Bonet I, Suardíaz R, Galarza C, Morales N, Leddermann V, Castro RI, Benso B, Urra G, Hernández-Rodríguez EW, Bustos D. Unveiling Novel Urease Inhibitors for Helicobacter pylori: A Multi-Methodological Approach from Virtual Screening and ADME to Molecular Dynamics Simulations. Int J Mol Sci 2024; 25:1968. [PMID: 38396647 PMCID: PMC10888695 DOI: 10.3390/ijms25041968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Revised: 01/20/2024] [Accepted: 01/25/2024] [Indexed: 02/25/2024] Open
Abstract
Helicobacter pylori (Hp) infections pose a global health challenge demanding innovative therapeutic strategies by which to eradicate them. Urease, a key Hp virulence factor hydrolyzes urea, facilitating bacterial survival in the acidic gastric environment. In this study, a multi-methodological approach combining pharmacophore- and structure-based virtual screening, molecular dynamics simulations, and MM-GBSA calculations was employed to identify novel inhibitors for Hp urease (HpU). A refined dataset of 8,271,505 small molecules from the ZINC15 database underwent pharmacokinetic and physicochemical filtering, resulting in 16% of compounds for pharmacophore-based virtual screening. Molecular docking simulations were performed in successive stages, utilizing HTVS, SP, and XP algorithms. Subsequent energetic re-scoring with MM-GBSA identified promising candidates interacting with distinct urease variants. Lys219, a residue critical for urea catalysis at the urease binding site, can manifest in two forms, neutral (LYN) or carbamylated (KCX). Notably, the evaluated molecules demonstrated different interaction and energetic patterns in both protein variants. Further evaluation through ADMET predictions highlighted compounds with favorable pharmacological profiles, leading to the identification of 15 candidates. Molecular dynamics simulations revealed comparable structural stability to the control DJM, with candidates 5, 8 and 12 (CA5, CA8, and CA12, respectively) exhibiting the lowest binding free energies. These inhibitors suggest a chelating capacity that is crucial for urease inhibition. The analysis underscores the potential of CA5, CA8, and CA12 as novel HpU inhibitors. Finally, we compare our candidates with the chemical space of urease inhibitors finding physicochemical similarities with potent agents such as thiourea.
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Affiliation(s)
- Paulina Valenzuela-Hormazabal
- Departamento de Farmacología, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción 4030000, Chile;
| | - Romina V. Sepúlveda
- Center for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andres Bello, Av. República 330, Santiago 8370146, Chile;
| | - Melissa Alegría-Arcos
- Núcleo de Investigación en Data Science, Facultad de Ingeniería y Negocios, Universidad de las Américas, Santiago 7500000, Chile;
| | - Elizabeth Valdés-Muñoz
- Doctorado en Biotecnología Traslacional, Facultad de Ciencias Agrarias y Forestales, Universidad Católica del Maule, Talca 3480094, Chile; (E.V.-M.); (V.R.-P.)
| | - Víctor Rojas-Pérez
- Doctorado en Biotecnología Traslacional, Facultad de Ciencias Agrarias y Forestales, Universidad Católica del Maule, Talca 3480094, Chile; (E.V.-M.); (V.R.-P.)
| | - Ileana González-Bonet
- Biomedical Research Labs, Facultad de Medicina, Universidad Católica del Maule, Talca 3480094, Chile;
| | - Reynier Suardíaz
- Departamento de Química Física, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, Spain;
| | - Christian Galarza
- Departamento de Matemáticas, Facultad de Ciencias Naturales y Matemáticas, Escuela Superior Politécnica del Litoral, Guayaquil 090112, Ecuador;
| | - Natalia Morales
- Magíster en Ciencias de la Computación, Universidad Católica del Maule, Talca 3460000, Chile; (N.M.); (V.L.)
| | - Verónica Leddermann
- Magíster en Ciencias de la Computación, Universidad Católica del Maule, Talca 3460000, Chile; (N.M.); (V.L.)
| | - Ricardo I. Castro
- Multidisciplinary Agroindustry Research Laboratory, Instituto de Ciencias Aplicadas, Facultad de Arquitectura, Construcción y Medio Ambiente, Universidad Autónoma de Chile, Cinco Pte. N°1670, Talca 3467987, Chile;
| | - Bruna Benso
- School of Dentistry, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 7810000, Chile;
| | - Gabriela Urra
- Laboratorio de Bioinformática y Química Computacional, Departamento de Medicina Traslacional, Facultad de Medicina, Universidad Católica del Maule, Talca 3480094, Chile;
| | - Erix W. Hernández-Rodríguez
- Laboratorio de Bioinformática y Química Computacional, Departamento de Medicina Traslacional, Facultad de Medicina, Universidad Católica del Maule, Talca 3480094, Chile;
- Unidad de Bioinformática Clínica, Centro Oncológico, Facultad de Medicina, Universidad Católica del Maule, Talca 3480094, Chile
| | - Daniel Bustos
- Laboratorio de Bioinformática y Química Computacional, Departamento de Medicina Traslacional, Facultad de Medicina, Universidad Católica del Maule, Talca 3480094, Chile;
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Paresi CJ, Liu Q, Li YM. Benzimidazole covalent probes and the gastric H(+)/K(+)-ATPase as a model system for protein labeling in a copper-free setting. MOLECULAR BIOSYSTEMS 2017; 12:1772-80. [PMID: 26952080 DOI: 10.1039/c6mb00024j] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Affinity probes are useful tools for determining molecular targets and elucidating mechanism of action for novel, bioactive compounds. In the case of covalent inhibitors, activity based probes are particularly valuable for ensuring acceptable selectivity margins. However, there is a variety of bioorthogonal chemistry reactions available for modifying compounds of interest with clickable tags. Here, we describe a direct comparison of tetrazine ligation and strain promoted azide-alkyne cycloaddition using benzimidazole based probes to bind their known target, the gastric proton pump, ATP4A. This study validates the use of chemical probes for target identification and illustrates the superior efficiency of tetrazine ligation for copper-free click systems. In addition, we have identified several novel binding partners of benzimidazole probes: Isoform 2 of deleted in malignant brain tumors 1 protein (DMBT1) and three uncharacterized proteins.
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Affiliation(s)
- Chelsea J Paresi
- Chemical Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. and Program of Pharmacology, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021, USA
| | - Qi Liu
- Chemical Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
| | - Yue-Ming Li
- Chemical Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. and Program of Pharmacology, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021, USA
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Tong YF, Lv J, Ying LY, Xu F, Qin B, Chen MT, Meng F, Tu MY, Yang NM, Li YM, Zhang JZ. Seven-day triple therapy is a better choice for Helicobacter pylori eradication in regions with low antibiotic resistance. World J Gastroenterol 2015; 21:13073-13079. [PMID: 26672777 PMCID: PMC4674725 DOI: 10.3748/wjg.v21.i46.13073] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2015] [Revised: 09/10/2015] [Accepted: 10/20/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate whether 7-d triple therapies are still valid in populations with low levels of resistance.
METHODS: A total of 1106 Helicobacter pylori (H. pylori)-positive patients were divided into three groups, each of which received one type of 7-d triple therapy. Therapeutic outcomes of the patients were assessed by the 13C-urea breath test at 8 wk after treatment. The susceptibility of H. pylori to antibiotics was determined by an agar-dilution method. Data analysis was performed by χ2 tests.
RESULTS: The eradication rates in groups A, B and C were 90.71% (332/366), 90.46% (313/346) and 90.87% (189/208), respectively (P = 0.986). The resistance rates were 8.91% for clarithromycin, 14.78% for levofloxacin and 0% for amoxicillin. The eradication rate was significantly different between clarithromycin- and levofloxacin-resistant patients (P < 0.05) in group A. Patients whose treatment failed in group A also had a higher clarithromycin resistance rate than did successive patients (P = 0.034). However, levofloxacin resistance had no obvious influence on the eradication rate. Furthermore, three main antibiotics (clarithromycin, levofloxacin and amoxicillin) had lower DID (defined daily dose per 1000 inhabitants per day) in this city.
CONCLUSION: Clarithromycin resistance is the main reason for the failure of 7-d triple therapy. In populations with low levels of resistance, a 7-d triple therapy is a viable choice. The choice of therapy should not be influenced by conditions in high antibiotic resistance regions.
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Kim SY, Choi DJ, Chung JW. Antibiotic treatment for Helicobacter pylori: Is the end coming? World J Gastrointest Pharmacol Ther 2015; 6:183-198. [PMID: 26558152 PMCID: PMC4635158 DOI: 10.4292/wjgpt.v6.i4.183] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 08/01/2015] [Accepted: 09/28/2015] [Indexed: 02/06/2023] Open
Abstract
Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori) has been associated with gastro-duodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacillus. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication.
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Zullo A, Ridola L, Francesco VD, Gatta L, Hassan C, Alvaro D, Bellesia A, de Nucci G, Manes G. High-dose esomeprazole and amoxicillin dual therapy for first-line Helicobacter pylori eradication: a proof of concept study. Ann Gastroenterol 2015; 28:448-51. [PMID: 26423014 PMCID: PMC4585390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND The prevalence of resistance to clarithromycin and metronidazole has considerably increased, with a corresponding decrease in the eradication rate for Helicobacter pylori (H. pylori) infection. Primary resistance to amoxicillin is extremely low, and esomeprazole was found to exert a noteworthy antimicrobial activity in vitro against H. pylori. A dual therapy with high-dose of esomeprazole coupled with high-dose amoxicillin might be therefore an ideal first-line treatment for H. pylori eradication. We aimed to assess the efficacy of a first-line 10-day, high-dose dual therapy consisting of amoxicillin and esomeprazole to eradicate H. pylori infection. METHODS Consecutive naïve H. pylori-infected patients, who underwent an upper endoscopy in 4 Italian hospitals due to dyspeptic symptoms and found to be infected at routine histological assessment, were invited to participate. Patients enrolled received a 10-day, high-dose dual therapy comprising esomeprazole (40 mg t.i.d) and amoxicillin (1 g t.i.d.). At least 4 weeks after the end of the treatment a (13)C-urea breath test was performed to evaluate the eradication. RESULTS A total of 56 patients agreed to participate in the study and were all followed-up. The overall eradication was 87.5% (95% CI=78.8•96.2), without a statistically significant difference among centres. Overall, 5 (8.9%; 1.5•16.4%) patients complained of side-effects. CONCLUSIONS The 10-day, high-dose dual therapy with esomeprazole and amoxicillin might be an effective and safe first-line regimen. The efficacy of a longer 14-day regimen should be tested.
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Affiliation(s)
- Angelo Zullo
- Gastroenterology and Digestive Endoscopy, ‘Nuovo Regina Margherita’ Hospital, Rome (Angelo Zullo, Cesare Hassan), Italy,
Correspondence to: Dr. Angelo Zullo, Gastroenterologia ed Endoscopia Digestiva, PTP Nuovo Regina Margherita, Via E. Morosini 30, 00153 Rome, Italy, Tel.: +39 06 5844 6608, Fax: +39 06 58446533, e-mail:
| | - Lorenzo Ridola
- Gastroenterology Unit, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome (Lorenzo Ridola), Italy
| | - Vincenzo De Francesco
- Gastroenterology Unit, ‘Riuniti’ Hospital, Foggia (Vincenzo De Francesco, Annamaria Bellesia), Italy
| | - Luigi Gatta
- Gastroenterology and Endoscopy Unit, Versilia Hospital, Lido di Camaiore (Luigi Gatta), Italy
| | - Cesare Hassan
- Gastroenterology and Digestive Endoscopy, ‘Nuovo Regina Margherita’ Hospital, Rome (Angelo Zullo, Cesare Hassan), Italy
| | - Domenico Alvaro
- Gastroenterology Unit, Sapienza University of Rome “Polo Pontino” Hospital, Latina (Domenico Alvaro), Italy
| | - Annamaria Bellesia
- Gastroenterology Unit, ‘Riuniti’ Hospital, Foggia (Vincenzo De Francesco, Annamaria Bellesia), Italy
| | - Germana de Nucci
- Department of Gastroenterology “Salvini” Hospital, Garbagnate, Milan (Germana de Nucci, Gianpiero Manes), Italy
| | - Gianpiero Manes
- Department of Gastroenterology “Salvini” Hospital, Garbagnate, Milan (Germana de Nucci, Gianpiero Manes), Italy
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Emami MH, Zobeiri M, Rahimi H, Arjomandi F, Daghagzadeh H, Adibi P, Hashemi J. N-acetyl cysteine as an adjunct to standard anti-Helicobacter pylori eradication regimen in patients with dyspepsia: A prospective randomized, open-label trial. Adv Biomed Res 2014; 3:189. [PMID: 25298958 PMCID: PMC4189211 DOI: 10.4103/2277-9175.140403] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2012] [Accepted: 12/12/2012] [Indexed: 12/29/2022] Open
Abstract
Background: Increasing antibiotic resistance of Helicobacter pylori (H. pylori) which is associated with diseases of the upper gastrointestinal tract, has made alternative treatments necessary. This study compares the efficacy of adding N-acetyl cysteine (NAC) to standard regimen for H. pylori eradication. Materials and Methods: We conducted a randomized, open-label trial, comparing the efficacy of 14 days of quadruple therapy with Amoxicillin, Bismuth citrate, Omeprazole, Clarithromycin (group A) versus 14 days of above regimen plus NAC (group B) in adult patients with dyspepsia. Primary objective was H. pylori eradication. Compliance and side effects were determined by questionnaires. Our analysis was by intention-to-treat (ITT) and per-protocol. This study is registered with www.IRCT.ir, number: IRCT201201078634N1. Result: A total of 121 participants aged 21-76 years with a mean age of 44.5 ± 14.1, and 52.9% female, were randomly allocated a treatment: 60 with 14-day standard therapy and 61 with 14-day standard therapy with NAC. The eradication rate in groups A and B with ITT analyses was 49/60 (81.7%; 95% [confidence intervals] CI = 71.6-91.8%) and 50/61 (82%; 95% CI = 72-91.9%), respectively (P = 0.96). In per-protocol analysis, the rate of H. pylori eradication in groups A and B was 45/54 (83.3%; 95% CI = 73.1-93.6%) and 45/53 (84.9%; 95% CI = 74.9-94.9%), respectively (P = 0.82). Minor well tolerated side effects were reported in 15 (34.9%) and 21 (35.6%) patients of groups A and B, respectively, and only one therapy cessation in group A was created. Conclusion: Standard 14-day triple-drug therapy with NAC is not preferable to standard drug regimens for H. pylori infection.
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Affiliation(s)
- Mohammad Hassan Emami
- Poursina Hakim Research Center Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehdi Zobeiri
- Kermanshah University of Medical Sciences, Kermanshah, Iran
| | | | - Fariba Arjomandi
- Department of Community Medicine, Islamic Azad University, Najafabad Branch, Iran
| | - Hamed Daghagzadeh
- Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Peyman Adibi
- Poursina Hakim Research Center Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Jalal Hashemi
- Department of Gastroenterology and Liver Disease, Ahvaz University of Medical Sciences, Ahvaz, Iran
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Zullo A, Ridola L, Efrati C, Giorgio F, Nicolini G, Cannaviello C, Alvaro D, Hassan C, Gatta L, Francesco VD. First- and second-line Helicobacter pylori eradication with modified sequential therapy and modified levofloxacin-amoxicillin-based triple therapy. Ann Gastroenterol 2014; 27:357-361. [PMID: 25330819 PMCID: PMC4188933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2014] [Accepted: 05/07/2014] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) treatment remains a challenge for physicians. Although highly effective, the standard sequential therapy fails in a certain number of patients. Moreover, the cure rate following a levofloxacin-amoxicillin second-line triple therapy seems to be decreasing. We tested the efficacy of modified 10-day sequential therapy, and an intensified levofloxacin-amoxicillin regimen as first- and second-line therapy respectively. METHODS In this prospective, open label, multicenter, pilot study H. pylori-infected patients received a first-line modified 10-day sequential therapy regimen including rabeprazole 20 mg, and amoxicillin 1 g for the first 3 days, followed by rabeprazole 20 mg, clarithromycin 250 mg, and metronidazole 250 mg, for the remaining 7 days, all drugs given thrice daily. An 8-day therapy regimen with rabeprazole 20 mg, levofloxacin 250 mg, and amoxicillin 1 g, all thrice daily, was administered a second-line therapy. RESULTS A total of 99 and 15 patients were enrolled for first- and second-line therapy. The eradication rates were 85.9% (95% CI 80-93) and 93.4% (95% CI 88-98) according to ITT and PP analyses following modified sequential therapy, and 60% (95% CI 35-86) and 64.3% (95% CI 39-89) following the intensified second-line therapy. CONCLUSION A modified sequential 3- plus 7-day regimen with thrice daily drug administration failed to achieve very high eradication rate at ITT analysis. The intensified second-line regimen achieved disappointingly low eradication rate. Novel levofloxacin-free second-line therapies are urged in Italy.
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Affiliation(s)
- Angelo Zullo
- Gastroenterology and Digestive Endoscopy, “Nuovo Regina Margherita” Hospital Rome (Angelo Zullo, Cesare Hassan), Italy
| | - Lorenzo Ridola
- Gastroenterology Unit, Sapienza University of Rome, “Polo Pontino” Hospital, Latina (Lorenzo Ridola, Domenico Alvaro), Italy
| | - Cesare Efrati
- Gastroenterology and Digestive Endoscopy, Israelitic Hospital, Rome (Cesare Efrati, Giorgia Nikolini, Claudio Cannaviello), Italy
| | - Floriana Giorgio
- Endoscopy Unit, Ruiniti Hospital, Foggia (Floriana Giorgio, Vincenzo De Francesco), Italy
| | - Giorgia Nicolini
- Gastroenterology and Digestive Endoscopy, Israelitic Hospital, Rome (Cesare Efrati, Giorgia Nikolini, Claudio Cannaviello), Italy
| | - Claudio Cannaviello
- Gastroenterology and Digestive Endoscopy, Israelitic Hospital, Rome (Cesare Efrati, Giorgia Nikolini, Claudio Cannaviello), Italy
| | - Domenico Alvaro
- Gastroenterology Unit, Sapienza University of Rome, “Polo Pontino” Hospital, Latina (Lorenzo Ridola, Domenico Alvaro), Italy
| | - Cesare Hassan
- Gastroenterology and Digestive Endoscopy, “Nuovo Regina Margherita” Hospital Rome (Angelo Zullo, Cesare Hassan), Italy
| | - Luigi Gatta
- Gastroenterology and Digestive Endoscopy; “Versilia” Hospital, Lido di Camaiore (Luigi Gatta), Italy
| | - Vincenzo De Francesco
- Endoscopy Unit, Ruiniti Hospital, Foggia (Floriana Giorgio, Vincenzo De Francesco), Italy
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Gazi S, Karameris A, Christoforou M, Agnantis N, Rokkas T, Stefanou D. Real-Time PCR detection and quantitation of Helicobacter pylori clarithromycin-resistant strains in archival material and correlation with Sydney classification. Ann Gastroenterol 2013; 26:226-232. [PMID: 24714278 PMCID: PMC3959441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2012] [Accepted: 01/25/2013] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori), infects gastric mucosa causing gastritis. Treatment failure is mainly due to certain genetic changes in the peptidyltransferase loop of 23S rRNA of the microorganism. The aim of the study was to evaluate genetic changes in gastric biopsies of H. pylori (+) patients that lead to clarithromycin resistance and to correlate them with histology data. METHODS A total of 150 H. pylori (+) gastric biopsies were studied, taken before and after eradication therapy from 75 dyspeptic patients divided in 2 groups: group A consisted of 25 H. pylori (+) triple-therapy resistant patients and group B consisted of 50 H. pylori (+) successfully treated patients. Histological classification of the H. pylori (+) gastritis was done according to the Sydney criteria. Genetic material was analyzed with the ClariRes™ RT-PCR bi-probe based assay for the determination of point mutations in the 23S rRNA gene and with a Quantitative-RT-PCR (Q-RT-PCR) method for the quantitation of H. pylori. RESULTS We showed that in 18/ 25 group A patients certain point mutations of 23S rRNA at sites A2142C, A2142G and A2143G had occurred. Nine of these 18 mutated cases (50%) were characterized as mixed infections. Mixed infections in 2/50 patients of group B were also observed. Using Q-RT-PCR, we found that gastric mucosal density of H. pylori correlates well with bacterial colonization. There was a statistically significant association (P<0.005) between the presence of the detected H. pylori genetic alterations and inflammation, activity and H. pylori density as histologically determined. CONCLUSION Certain point mutations in H. pylori genome that affect susceptibility to clarithromycin correlate with histological features of gastritis.
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Affiliation(s)
- Sofia Gazi
- National Organization for Medicines, Micobiology Lab, Athens, Greece (Sofia Gazi)
| | - Andreas Karameris
- Department of Pathology, NIMTS Hospital, Athens, Greece (Andreas Karameris),
Correspondence to: Andreas Karameris, MD, PhD, Dept. of Pathology, NIMTS Hospital, Athens, Greece, Tel.: +30 210 7288357, Fax: +30 210 7297977, e-mail:
| | | | - Niki Agnantis
- Department of Pathology, University of Ioannina, Greece (Dimitrios Stefanou, Niki Agnantis)
| | - Theodore Rokkas
- Gastroenterology Unit, Henry Dunant Hospital, Athens, Greece (Theodore Rokkas)
| | - Dimitrios Stefanou
- Department of Pathology, University of Ioannina, Greece (Dimitrios Stefanou, Niki Agnantis)
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