[Argentinean registry on the management of Helicobacter pylori infection: effectiveness and safety of first line treatment]. / Registro argentino para el manejo de la infección por Helicobacter pylori: efectividad y seguridad de los esquemas de primera línea de tratamiento.

INTRODUCTION: The optimal management of Helicobacter pylori (H pylori) infection remains unclear. Updated information concerning local data is needed to design the best strategy to treat H. pylori infection to reach high eradication rates. The Argentinean Registry (Hp-ArgReg) on H. pylori management was launched to monitor the eradication practices of gastroenterologists. The objective was to assess the effectiveness and safety of firstline H. pylori treatment in Argentina. MATERIALS AND METHODS: A multicenter prospective registry of the clinical practice of the Argentinean gastroenterologists concerning H. pylori infection (Hp-ArgReg) was developed. Variables included: patient demographic information, previous eradication attempts, prescribed treatment, adverse events, compliance and outcome. RESULTS: Overall, 800 patients were included and 727 patients received first-line empirical treatment. The most frequent treatment indications were dyspepsia (78%) and gastroduodenal ulcer (12%). Among first-line treatments, quadruple therapies (with or without bismuth) achieved eradication rates of 94.9%, while triple therapies achieved eradication rates of 78.9%. Quadruple therapies were significantly more effective than triple therapies (P < 0.01, OR 5, CI 2.95-8.6). Sequential therapy with zinc showed an effectiveness of 95.6%. Adverse events were reported in 29% of the cases (mainly mild) and tolerance was quite similar among therapies. CONCLUSION: in Argentina, Quadruple therapies with or without bismuth and sequential therapy with zinc showed an H. pylori eradication effectiveness of over 90% in real clinical practice. Local Registries for H pylori management could help to control the spread of antibiotic resistance.

Introducción: El óptimo manejo de la infección por Helicobacter pylori (H. pylori) es objeto de debate. Contar con datos locales ayudaría a lograr altas tasas de erradicación. El Registro Argentino H. pylori (RegArg-Hp) se estableció con el objetivo de monitorear el manejo local de la infección. El objetivo fue describir la efectividad y seguridad de las terapias empíricas de primera línea para la erradicación del H. pylori utilizadas en Argentina. Materiales y métodos: Registro prospectivo, multicéntrico, de la práctica clínica de los gastroenterólogos argentinos. Se incluyeron datos demográficos de pacientes con infección por H. pylori, intentos previos de erradicación, tratamiento indicado, eventos adversos, cumplimiento y erradicación. Resultados: De 800 pacientes incluidos, 727 recibieron un tratamiento empírico de primera línea. Las indicaciones de tratamiento más frecuentes fueron dispepsia (78%) y úlcera gastroduodenal (12%). Entre los tratamientos de primera línea, las terapias cuádruples (con o sin bismuto) lograron tasas de erradicación del 94.9% mientras las terapias triples tasas de erradicación del 78.9%. Las terapias cuádruples fueron significativamente más efectivas que las triples (P < 0.01, OR 5, IC 2.95-8.6). La terapia secuencial con zinc mostró una efectividad del 95.6%. Se reportaron eventos adversos en el 29% de los pacientes, generalmente leves y con una tolerancia similar entre las diferentes terapias. Conclusiones: En Argentina, las terapias cuádruples con o sin bismuto y la secuencial con zinc presentaron una efectividad de erradicación de H. pylori superior al 90%. La implementación de registros locales podría contribuir al control de la resistencia a los antibióticos.

Relationship between obesity severity and Helicobacter pylori eradication in patients undergoing bariatric and metabolic surgery: A post hoc analysis.

BACKGROUND: The global prevalence of obesity is increasing and represents a major public health challenge. However, there is a paucity of data regarding Helicobacter pylori (H pylori) eradication in people with obesity. The aim of the study is to examine the influence of obesity degree on H. pylori eradication in patients undergoing bariatric and metabolic surgery. METHODS: A post hoc analysis was conducted in a cohort of 204 adults patients (129 individuals diagnosed with obesity, 75 normal weight) H. pylori positive, included in two multicenter, prospective studies. Patients underwent a 14-day quadruple concomitant treatment, and H. pylori eradication was assessed using the 13C-urea breath test. The cohort was stratified according to body mass index (BMI), and statistical analyses were performed using chi-squared test, Kruskal-Wallis test, and logistic regression. RESULTS: Eradication rates were significantly lower in patients with obesity compared with normal weight individuals (68.2% vs. 88.0%, OR 0.29, 95% CI 0.13-0.63, p < 0.01). Furthermore, within the population diagnosed with obesity, the degree of obesity correlated with decreased eradication rates, with class 3 (BMI 40.0-49.9) and class 4 (BMI ≥ 50.0) obesity showing the lowest rates (67% and 51%, with an OR 0.28 and 0.15 respectively, p < 0.01). CONCLUSIONS: Our results indicate that obesity may influence H. pylori eradication, especially among severe obesity patients undergoing bariatric surgery, which could have implications for the development of ulcers and gastritis as well as the risk of gastric cancer. Tailored eradication strategies may be necessary to improve treatment efficacy in this population.

Helicobacter pylori in oral cavity: current knowledge.

The oral cavity may play a role as a reservoir and in the transmission and colonization of Helicobacter pylori. The route of transmission for H. pylori is not fully understood. The prevalence of this pathogen varies globally, affecting half of the world's population, predominantly in developing countries. Here, we review the prevalence of H. pylori in the oral cavity, the characteristics that facilitate its colonization and dynamics in the oral microbiome, the heterogeneity and diversity of virulence of among strains, and noninvasive techniques for H. pylori detection in oral samples. The prevalence of H. pylori in the oral cavity varies greatly, being influenced by the characteristics of the population, regions where samples are collected in the oral cavity, and variations in detection methods. Although there is no direct association between the presence of H. pylori in oral samples and stomach infection, positive cases for gastric H. pylori frequently exhibit a higher prevalence of the bacterium in the oral cavity, suggesting that the stomach may not be the sole reservoir of H. pylori. In the oral cavity, H. pylori can cause microbiome imbalance and remodeling of the oral ecosystem. Detection of H. pylori in the oral cavity by a noninvasive method may provide a more accessible diagnostic tool as well as help prevent transmission and gastric re-colonization. Further research into this bacterium in the oral cavity will offer insights into the treatment of H. pylori infection, potentially developing new clinical approaches.

Genomic insights into the antimicrobial resistance and virulence of Helicobacter pylori isolates from gastritis patients in Pereira, Colombia.

BACKGROUND: Helicobacter pylori infects the stomach and/or small intestines in more than half of the human population. Infection with H. pylori is the most common cause of chronic gastritis, which can lead to more severe gastroduodenal pathologies such as peptic ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. H. pylori infection is particularly concerning in Colombia in South America, where > 80% of the population is estimated to be infected with H. pylori and the rate of stomach cancer is one of the highest in the continent. RESULTS: We compared the antimicrobial susceptibility profiles and short-read genome sequences of five H. pylori isolates obtained from patients diagnosed with gastritis of varying severity (chronic gastritis, antral erosive gastritis, superficial gastritis) in Pereira, Colombia sampled in 2015. Antimicrobial susceptibility tests revealed the isolates to be resistant to at least one of the five antimicrobials tested: four isolates were resistant to metronidazole, two to clarithromycin, two to levofloxacin, and one to rifampin. All isolates were susceptible to tetracycline and amoxicillin. Comparative genome analyses revealed the presence of genes associated with efflux pump, restriction modification systems, phages and insertion sequences, and virulence genes including the cytotoxin genes cagA and vacA. The five genomes represent three novel sequence types. In the context of the Colombian and global populations, the five H. pylori isolates from Pereira were phylogenetically distant to each other but were closely related to other lineages circulating in the country. CONCLUSIONS: H. pylori from gastritis of different severity varied in their antimicrobial susceptibility profiles and genome content. This knowledge will be useful in implementing appropriate eradication treatment regimens for specific types of gastritis. Understanding the genetic and phenotypic heterogeneity in H. pylori across the geographical landscape is critical in informing health policies for effective disease prevention and management that is most effective at local and country-wide scales. This is especially important in Colombia and other South American countries that are poorly represented in global genomic surveillance studies of bacterial pathogens.

Association between the presence of Helicobacter pylori and the development of de novo anemia in adults undergoing sleeve gastrectomy.

Background: Sleeve gastrectomy has gained prominence in obesity treatment, yet it is not without complications, such as the development of anemia in the medium term. Given the high prevalence of Helicobacter pylori infection in Peru, it is imperative to explore its potential association with this postoperative complication. Objective: To evaluate the association between the presence of Helicobacter pylori and the development of anemia 12 months after sleeve gastrectomy. Methods: A retrospective cohort study was carried out based on an analysis of secondary data from a private clinic in Lima, Peru, which included two groups of people over 18 years of age who had undergone sleeve gastrectomy between 2010 and 2020. We considered the subjects who had the previous diagnosis of Helicobacter pylori as well as those who did not have the infection, according to the detection of the bacteria by endoscopy before surgery. Results: A total 313 individuals were analyzed, and it was found that the prevalence of Helicobacter pylori was 46.0% and the incidence of anemia 12 months after sleeve gastrectomy was 18.2%. The presence of Helicobacter pylori increased the risk of de novo anemia (Relative Risk = 1.56; 95% confidence intervals: 1.02-2.41; p = 0.043). When stratifying by sex, the association was maintained only for the male group (Relative Risk = 2.84; 95% confidence intervals: 1.02-7.02; p = 0.047). Conclusions: It was identified that the presence of Helicobacter pylori had a significant association with the development of de novo anemia, mainly in male subjects, 1 year after undergoing sleeve gastrectomy.

Synthesis of Chalcones, Screening In silico and In vitro and Evaluation of Helicobacter pylori Adhesion by Molecular Docking.

AIMS: We synthetized 10 hydroxylated and methoxylated chalcones and evaluated them targeting MMP-9 inhibition, looking for the rate of adhesion of H. pylori in gastric cells, and then, reduction of the inflammatory response as alternative therapeutic agents for controlling the infection. BACKGROUND: Helicobacter pylori is a Gram-negative bacterium that chronically infects the human stomach, a risk factor for the development of inflammatory gastrointestinal diseases, including cancer, and is classified as a group I carcinogen. It is estimated that it infects around 45% of the global population and that the persistence of the infection is related to the adhesion of the bacteria in the gastric epithelium. The progression of gastric lesions to cancer is connected to the activation of the NF-κB and MAPK pathways, especially in cagA+ strains, which are related to increased expression of MMP-9. The activation of these metalloproteinases (MMPs) contributes to the adhesion of the bacterium in gastric cells and the evolving stages of cancer, such as enabling metastasis. Due to the increasing resistance to the current therapy protocols, the search for alternative targets and candidate molecules is necessary. In this way, controlling adhesion seems to be a suitable option since it is a crucial step in the installation of the bacterium in the gastric environment. OBJECTIVE: Synthetize ten hydroxylated and methoxylated chalcones. Assess their anti-H. pylori potential, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). Evaluate their cytotoxicity in AGS cells and selectivity with L-929 cells. Analyze the results and correlate them with in silico predictions to evaluate potential anti-adhesive properties for the chalcones against H. pylori. METHODS: The chalcones were synthetized by Claisen-Schmidt condensation using Ba(OH)2 or LiOH as catalysts. Predictive in silico assays in PASS Online, tanimoto similarity, ADME properties and molecular docking in MMP-9 (PDB code: 6ESM) were performed. The in vitro assays carried out were the cell viability in gastric adenocarcinoma cells (AGS) and fibroblasts (L-929) by the MMT method and anti-H. pylori, by the broth microdilution method, through the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). RESULTS: Ten chalcones were synthesized through Claisen-Schimdt condensation with yields of 10 to 52% and characterized by 1H and 13C nuclear magnetic resonance (NMR) and mass spectrometry (MS). in silico data revealed the possibility of anti-H. pylori, anti-inflammatory, and MMP-9 inhibition for the chalcones. Chalcone 9 showed the best growth inhibition values for MIC and MBC, at 1 µg/mL and 2 µg/mL, respectively. Chalcones 14 and 15 likewise demonstrated excellent inhibitory results, being 2 µg/mL for both MIC and MBC. Additionally, 15 had the best MMP-9 inhibition score. Despite not corroborating the in silico findings, chalcones 10, 13, and 18 showed good cytotoxicity and the best selectivity indices. CONCLUSION: All compounds exhibited strong activity against H. pylori, specially 15. The predicted MMP-9 inhibition by molecular docking added to the reasonable SI and CI50 values for 15 and the satisfactory reduction in the rate of survival of the bacteria, reveals that it may be acting synergically to reduce the inflammatory response and the possibilities for developing a tumor by inhibiting both bacteria and malignant cells.

Association between Helicobacter pylori antibodies and otolaryngological diseases.

OBJECTIVE: Observational studies have shown that Helicobacter pylori is related to some otolaryngological diseases. However, it is unclear if H. pylori infection causally affects these diseases. To elucidate H. pylori role in 12 common otolaryngological diseases, we conducted two-sample Mendelian randomization analysis. METHODS: Single-nucleotide polymorphisms associated with 7 H. pylori antibodies (IgG, CagA, Catalase, GroEL, OMP, UREA and Vac A) served as instrumental variables. We primarily employed random-effects inverse variance weighting for causal estimation, supplemented by MR Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses, including heterogeneity, pleiotropy, and leave-one-out tests, validated robustness. RESULTS: MR analysis using inverse variance weighting (random effects) revealed genetically predicted H. pylori CagA antibodies correlated with increased risk of nonsuppurative otitis media (OR = 1.0778, 95% CI 1.0114-1.1487, p-value = 0.021). No causal relationship was observed between H. pylori antibodies and other common otolaryngological diseases. Sensitivity analyses found no pleiotropy or heterogeneity, affirming result reliability. CONCLUSION: This study suggests that the levels of H. pylori CagA antibodies may contribute to the development of nonsuppurative otitis media. Further studies are needed in the future to elucidate the specific mechanism of H. pylori in this disease. LEVEL OF EVIDENCE: Level III.

Helicobacter pylori cagA/vacAs1-m1 strain is associated with high risk of fibrosis in metabolic-dysfunction-associated steatotic liver disease.

INTRODUCTION AND OBJECTIVES: Recent studies have suggested an association between H. pylori and metabolic dysfunction associated steatotic liver disease (MASLD). We aim to evaluate the association of H. pylori virulence genes with non-invasive markers of liver injury and fibrosis in MASLD subjects. PATIENTS AND METHODS: A total of 362 dyspeptic patients who underwent gastroscopy were selected. Biochemical, clinical parameters, ultrasound, FIB-4 score, liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE), gastric biopsies, and H. pylori virulence genes (cagA, vacA) were evaluated. RESULTS: A cohort comprised of 61 % women and 39 % men with a median age of 52 (40-60) years. MASLD was observed in 42 %, and H. pylori-positive in 45 %. No differences were observed regarding H. pylori status at co-morbid metabolic conditions. In MASLD cohort, H. pylori-positive was associated with higher AST, ALT, FIB-4 and LSM. Indeed, carriers of cagA/vacA-s1/m1-positive allelic combination were associated with higher AST, ALT, FIB-4 and LSM but not cagA/vacA-s1/m1-negative. The OR for high-risk of significant/advanced- fibrosis by VCTE (≥8 kPa) with H. pylori-positive was 2.56 (95 % CI, 1.2-5.75) and for cagA/vacA-s1/-m1-positive allelic carriers was 4.01 (95 % CI, 1.38-11.56), but non-significant association in cagA/vacA-s1/-m1-negative. After adjusting for age, gender, diabetes, BMI and hypertension the OR for VCTE ≥8 kPa with H. pylori-positive was 2.43 (95 % CI, 1.88-12.44), and cagA/vacA-s1/m1-positive allelic carriers was 4.06 (95 % CI, 1.22-14.49). CONCLUSIONS: In our cohort of functional dyspepsia (FD) patients with MASLD, H. pylori was associated with non-invasive markers of liver injury and fibrosis. Carriers of cagA/vacA-s1/m1-positive allelic combination showed an independent risk of significant/advanced fibrosis by VCTE.

Synthesis and anti-ureolitic activity of Biginelli adducts derived from formylphenyl boronic acids.

Urease is a metalloenzyme that contains two Ni(II) ions in its active site and catalyzes the hydrolysis of urea into ammonia and carbon dioxide. The development of effective urease inhibitors is crucial not only for mitigating nitrogen losses in agriculture but also for offering an alternative treatment against infections caused by resistant pathogens that utilize urease as a virulence factor. This study focuses on synthesizing and investigating the urease inhibition potential of Biginelli Adducts bearing a boric acid group. An unsubstituted or hydroxy-substituted boronic group in the Biginelli adducts structure enhances the urease inhibitory activity. Biophysical and kinetics studies revealed that the best Biginelli adduct (4e; IC50 = 132 ± 12 µmol/L) is a mixed inhibitor with higher affinity to the urease active site over an allosteric one. Docking studies confirm the interactions of 4e with residues essential for urease activity and demonstrate its potential to coordinate with the nickel atoms through the oxygen atoms of carbonyl or boronic acid groups. Overall, the Biginelli adduct 4e shows great potential as an additive for developing enhanced efficiency fertilizers and/or for medical applications.

Quadruple therapies show a higher eradication rate compared to standard triple therapy for Helicobacter pylori infection within the LEGACy consortium. A multicenter observational study in European and Latin American countries.

INTRODUCTION: Gastric cancer (GC) is one of the most lethal malignancies worldwide. Helicobacter pylori is the primary cause of GC; therefore, its eradication reduces the risk of developing this neoplasia. There is extensive evidence regarding quadruple therapy with relevance to the European population. However, in Latin America, data are scarce. Furthermore, there is limited information about the eradication rates achieved by antibiotic schemes in European and Latin American populations. OBJECTIVE: To compare the effectiveness of standard triple therapy (STT), quadruple concomitant therapy (QCT), and bismuth quadruple therapy (QBT) in six centers in Europe and Latin America. METHODS: A retrospective study was carried out based on the LEGACy registry from 2017 to 2022. Data from adult patients recruited in Portugal, Spain, Chile, Mexico, and Paraguay with confirmed H. pylori infection who received eradication therapy and confirmatory tests at least 1 month apart were included. Treatment success by each scheme was compared using a mixed multilevel Poisson regression, adjusting for patient sex and age, together with country-specific variables, including prevalence of H. pylori antibiotic resistance (clarithromycin, metronidazole, and amoxicillin), and CYP2C19 polymorphisms. RESULTS: 772 patients were incorporated (64.64% females; mean age of 52.93 years). The total H. pylori eradication rates were 75.20% (255/339) with STT, 88.70% (159/178) with QCT, and 91.30% (191/209) with QBT. Both quadruple therapies (QCT-QBT) showed significantly higher eradication rates compared with STT, with an adjusted incidence risk ratio (IRR) of 1.25 (p: <0.05); and 1.24 (p: <0.05), respectively. The antibiotic-resistance prevalence by country, but not the prevalence of CYP2C19 polymorphism, showed a statistically significant impact on eradication success. CONCLUSIONS: Both QCT and QBT are superior to STT for H. pylori eradication when adjusted for country-specific antibiotic resistance and CYP2C19 polymorphism in a sample of individuals residing in five countries within two continents.

The Antibacterial Potential of Brazilian Red Propolis against the Formation and Eradication of Biofilm of Helicobacter pylori.

Helicobacter pylori is associated with gastrointestinal diseases, and its treatment is challenging due to antibiotic-resistant strains, necessitating alternative therapies. Brazilian red propolis (BRP), known for its diverse bioactive compounds with pharmaceutical properties, was investigated for its anti-H. pylori activity, focusing on biofilm formation inhibition and eradication. BRP was tested against H. pylori (ATCC 43526) using several assays: time-kill, nucleotide leakage, biofilm formation inhibition (determining the minimum inhibitory concentration of biofilm of 50%-MICB50, and cell viability), and biofilm eradication (determining the minimum eradication concentration of biofilm of 99.9%-MBEC). Standardization of H. pylori biofilm formation was also conducted. In the time-kill assay, BRP at 50 µg/mL eliminated all H. pylori cells after 24 h. The nucleotide leakage assay showed no significant differences between control groups and BRP-treated groups at 25 µg/mL and 50 µg/mL. H. pylori formed biofilms in vitro at 109 CFU/mL after 72 h. The MICB50 of BRP was 15.6 µg/mL, and at 500, 1000, and 2000 µg/mL, BRP eradicated all bacterial cells. The MBEC was 2000 µg/mL. These findings suggest that BRP has promising anti-H. pylori activity, effectively inhibiting and eradicating biofilms. Further studies are necessary to elucidate BRP's mechanisms of action against H. pylori.

Association between Helicobacter pylori infection, mismatch repair, HER2 and tumor-infiltrating lymphocytes in gastric cancer.

BACKGROUND: The influence of Helicobacter-pylori (H. pylori) infection and the characteristics of gastric cancer (GC) on tumor-infiltrating lymphocyte (TIL) levels has not been extensively studied. Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information. AIM: To determine the rates of deficient mismatch-repair (dMMR), HER2-status and H. pylori infection and their association with TIL levels in GC. METHODS: Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral (IT), stromal (ST) and invasive-border (IB) compartments. The density of CD3, CD8 and CD163 immune cells, and dMMR and HER2-status were determined by immunohistochemistry (IHC). H. pylori infection was evaluated by routine histology and quantitative PCR (qPCR) in a subset of samples. RESULTS: dMMR was found in 34.4%, HER2+ in 5% and H. pylori-positive in 55.7% of samples. High IT-TIL was associated with grade-3 (P = 0.038), while ST-TIL with grade-1 (P < 0.001), intestinal-histology (P < 0.001) and no-recurrence (P = 0.003). dMMR was associated with high TIL levels in the ST (P = 0.019) and IB (P = 0.01) compartments, and ST-CD3 (P = 0.049) and ST-CD8 (P = 0.05) densities. HER2- was associated with high IT-CD8 (P = 0.009). H. pylori-negative was associated with high IT-TIL levels (P = 0.009) when assessed by routine-histology, and with high TIL levels in the 3 compartments (P = 0.002-0.047) and CD8 density in the IT and ST compartments (P = 0.001) when assessed by qPCR. A longer overall survival was associated with low IT-CD163 (P = 0.003) and CD8/CD3 (P = 0.001 in IT and P = 0.002 in ST) and high IT-CD3 (P = 0.021), ST-CD3 (P = 0.003) and CD3/CD163 (P = 0.002). CONCLUSION: TIL levels were related to dMMR and H. pylori-negativity. Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

Antimicrobial Resistance of Helicobacter pylori Isolated From Latin American Children and Adolescents (2008-2023): A Systematic Review.

BACKGROUND: Latin America has a high prevalence of Helicobacter pylori in children that may lead to peptic ulcer disease and eventually gastric cancer in adulthood. Successful eradication is hindered by rising antimicrobial resistance. We summarize H. pylori resistance rates in Latin American children from 2008 to 2023. MATERIAL AND METHODS: Systematic review following PRISMA guidelines and National Heart, Lung, and Blood Institute checklist to assess risk of bias (PROSPERO CRD42024517108) that included original cross-sectional observational studies reporting resistance to commonly used antibiotics in Latin American children and adolescents. We searched in PubMed, LILACS, and SciELO databases. RESULTS: Of 51 studies, 45 were excluded. The quality of the six analyzed studies (297 H. pylori-positive samples) was satisfactory. Phenotypic methods (N = 3) reported higher resistance rates than genotypic studies (N = 3). Clarithromycin resistance ranged from 8.0% to 26.7% (6 studies; 297 samples), metronidazole from 1.9% to 40.2% (4 studies; 211 samples), amoxicillin from 0% to 10.4% (3 studies; 158 samples), tetracycline resistance was not detected (3 studies; 158 samples), and levofloxacin resistance was 2.8% (1 study; 36 samples). CONCLUSION: Scarce Latin American studies on H. pylori resistance, along with methodological heterogeneity, hinder conclusive findings. Clarithromycin and metronidazole (first-line drugs) resistance is worrisome, likely impacting lower eradication rates. Urgent systematic surveillance or individual testing before treatment is necessary to enhance eradication.

Point Mutations in Furazolidone and Rifampicin Resistance Genes in Helicobacter pylori Strains from Colombia.

The eradication of Helicobacter pylori is a valid strategy for preventing gastric cancer; however, the therapeutic failure of first-line treatments in Colombia is associated with high resistance to metronidazole and amoxicillin. This study explored alternative antibiotics and analyzed point mutations in resistance genes to furazolidone and rifampicin in order to include them in rescue therapy regimens. A total of 239 complete genomes of Helicobacter pylori Colombian strains were compared to that of the ATCC 26695 strain to identify mutations in the rpoB and porD genes for rifampicin and furazolidinone resistance, respectively. While rifampicin resistance mutations were not found, only 0.84% of the isolates showed the porD gene, suggesting that Helicobacter pylori is sensitive to these antibiotics. A phylogenomic analysis of Helicobacter pylori revealed an independent lineage in Colombia (hspColombia). The absence of point mutations in the rpoB gene, together with the scarce mutations identified in the porD gene of Helicobacter pylori, suggest that the hspColombia isolates are sensitive to rifampicin and furazolidone, which could be key to including these antibiotics in the rescue therapies against Helicobacter pylori.

Whole-genome sequences of Helicobacter pylori isolated from patients with high risk of gastric cancer in the Andes of Nariño, Colombia.

We sequenced the complete genomes of 16 Helicobacter pylori isolates obtained from patients residing in Nariño, Colombia. These isolates were collected from patients presenting various gastric lesions classified according to the Correa cascade classification. The genomic characterization of these isolates provides valuable insights into the structure, composition, and pathogenicity.

Pepsinogen I, pepsinogen II, gastrin-17, and Helicobacter pylori serological biomarkers in the diagnosis of precursor lesions of gastric cancer.

Introduction: Atrophic gastritis and intestinal metaplasia are precursor lesions of gastric cancer. The aim of this study was to determine the usefulness of the biomarkers pepsinogen I(PgI), pepsinogen II (PgII), gastrin-17, and H. pylori antibodies in the identification of precursor lesions. Methods: We studied 129 patients with gastric symptoms. The biomarker status was determined using GastroPanel by means of the ELISA-technique. Results: Biomarkers detected atrophy in 14% of the subjects, and 49.6% had positive antibodies for H. pylori. A PgI/PgII ratio < 3 was an important risk biomarker for precursor lesions in our population (OR = 9.171, 95% CI: 1.723-48.799, p = 0.009); however, biomarkers showed low accuracy with histopathological study. Conclusions: In the Western Mexican population, precursor lesions (AG, IM) are common in adults (45%) with dyspepsia but infrequent in children (8%). H. pylori infection was detected in 41.3% of adults and 16.0% of children. Of the studied biomarkers, a PgI/PgII ratio < 3 was an important risk factor for precursor lesions such as AG or IM in our population, with an OR of 9.171 (95% CI: 1.723-48.799, p = 0.009).

In silico prospective analysis of the medicinal plants activity on the CagA oncoprotein from Helicobacter pylori.

BACKGROUND: Colonization with Helicobacter pylori (H. pylori) has a strong correlation with gastric cancer, and the virulence factor CagA is implicated in carcinogenesis. Studies have been conducted using medicinal plants with the aim of eliminating the pathogen; however, the possibility of blocking H. pylori-induced cell differentiation to prevent the onset and/or progression of tumors has not been addressed. This type of study is expensive and time-consuming, requiring in vitro and/or in vivo tests, which can be solved using bioinformatics. Therefore, prospective computational analyses were conducted to assess the feasibility of interaction between phenolic compounds from medicinal plants and the CagA oncoprotein. AIM: To perform a computational prospecting of the interactions between phenolic compounds from medicinal plants and the CagA oncoprotein of H. pylori. METHODS: In this in silico study, the structures of the phenolic compounds (ligands) kaempferol, myricetin, quercetin, ponciretin (flavonoids), and chlorogenic acid (phenolic acid) were selected from the PubChem database. These phenolic compounds were chosen based on previous studies that suggested medicinal plants as non-drug treatments to eliminate H. pylori infection. The three-dimensional structure model of the CagA oncoprotein of H. pylori (receptor) was obtained through molecular modeling using computational tools from the I-Tasser platform, employing the threading methodology. The primary sequence of CagA was sourced from GenBank (BAK52797.1). A screening was conducted to identify binding sites in the structure of the CagA oncoprotein that could potentially interact with the ligands, utilizing the GRaSP online platform. Both the ligands and receptor were prepared for molecular docking using AutoDock Tools 4 (ADT) software, and the simulations were carried out using a combination of ADT and AutoDock Vina v.1.2.0 software. Two sets of simulations were performed: One involving the central region of CagA with phenolic compounds, and another involving the carboxy-terminus region of CagA with phenolic compounds. The receptor-ligand complexes were then analyzed using PyMol and BIOVIA Discovery Studio software. RESULTS: The structure model obtained for the CagA oncoprotein exhibited high quality (C-score = 0.09) and was validated using parameters from the MolProbity platform. The GRaSP online platform identified 24 residues (phenylalanine and leucine) as potential binding sites on the CagA oncoprotein. Molecular docking simulations were conducted with the three-dimensional model of the CagA oncoprotein. No complexes were observed in the simulations between the carboxy-terminus region of CagA and the phenolic compounds; however, all phenolic compounds interacted with the central region of the oncoprotein. Phenolic compounds and CagA exhibited significant affinity energy (-7.9 to -9.1 kcal/mol): CagA/kaempferol formed 28 chemical bonds, CagA/myricetin formed 18 chemical bonds, CagA/quercetin formed 16 chemical bonds, CagA/ponciretin formed 13 chemical bonds, and CagA/chlorogenic acid formed 17 chemical bonds. Although none of the phenolic compounds directly bound to the amino acid residues of the K-Xn-R-X-R membrane binding motif, all of them bound to residues, mostly positively or negatively charged, located near this region. CONCLUSION: In silico, the tested phenolic compounds formed stable complexes with CagA. Therefore, they could be tested in vitro and/or in vivo to validate the findings, and to assess interference in CagA/cellular target interactions and in the oncogenic differentiation of gastric cells.

Trichilia catigua against Helicobacter pylori: An in vitro, molecular and in silico approach.

Helicobacter pylori is a bacterium that is present in the stomach of about 50% of the global population and is associated with several gastric disorders, including cancer. Natural products with antimicrobial activity have been tested against H. pylori, among them Trichilia catigua (catuaba), which is widely distributed in Brazil. This study aimed to evaluate extracts of T. catigua bark against H. pylori via determination of the minimum inhibitory and bactericidal concentrations (MIC and MBC); evaluation of virulence factors by real-time PCR, synergism with standard antimicrobials and morphology by scanning electron microscopy and simulations of the mechanism of action by molecular docking. The ethyl acetate fraction provided the best results, with an MIC50 of 250 µg/mL and a 42.34% reduction in urease activity, along with reduced expression of the CagA and VacA genes, which encode for the main virulence factors. This fraction presented synergistic activity with clarithromycin, reducing the MIC of the drug by four-fold. Docking simulations suggested that the extracts inhibit fatty acid synthesis by the FAS-II system, causing damage to the cell membrane. Therefore, T. catigua extracts have potential as an adjuvant to treatment and are promising for the development of new anti-H. pylori drugs.

Antimicrobial susceptibility of clinical Helicobacter pylori isolates and its eradication by standard triple therapy: a study in west central region of Colombia.

The aim of the present study was first to isolate Helicobacter pylori from gastric biopsy specimens and to test their antibiotic susceptibility. Second, it was to evaluate the efficacy of the standard triple therapy from patients of the west central region of Colombia. H. pylori positive patients received standard triple therapy with proton pump inhibitor (PPI) (40 mg b.i.d.), clarithromycin (500 mg b.i.d.), and amoxicillin (1 g b.i.d.) for 14 days. Thereafter, antibiotic susceptibility of the isolates was assessed by E-Test. From 94 patients enrolled, 67 were positive for H. pylori by histology or culture. Overall resistance to metronidazole, levofloxacin, rifampicin, clarithromycin, and amoxicillin was 81%, 26.2%, 23.9%, 19%, and 9.5%, respectively. No resistance was found for tetracycline. A total of 54 patients received standard triple therapy, 48 attended follow-ups testing, and of them, 30 had resistance test reports. Overall eradication rate was 81.2%. Second-line treatment was given to eight patients, four of whom were followed up with a 13C urea breath test (UBT) and remained positive for H. pylori. Eradication was significantly higher in patients with clarithromycin susceptible than in resistant strains (95.6% vs 42.8% P = 0.001). The updated percentages of resistance to clarithromycin in this geographical area had increased, so this value must be considered when choosing the treatment regimen.IMPORTANCEAntibiotic resistance in Helicobacter pylori has increased worldwide, as has resistance to multiple antimicrobials (MDRs), which seriously hampers the successful eradication of the infection. The ideal success rate in eradicating H. pylori infection (≥90%) was not achieved in this study (81.2%). This is the first time that MDR is reported (14.3%) in the region; the resistance to clarithromycin increased over time (3.8%-19%), and levofloxacin (26.2%) and rifampicin (23%) resistant isolates were detected for the first time. With these results, strain susceptibility testing is increasingly important, and the selection of treatment regimen should be based on local antibiotic resistance patterns.

Reduction of Helicobacter pylori cells in rural water supply using slow sand filtration.

Helicobacter pylori is a microorganism that infects 60% of the population and is considered the main cause of atrophic gastritis, gastric and duodenal ulcers, and gastric cancer. Different emerging pathogens have been found in drinking water and their presence is considered to be an important public health problem. For this reason, it is necessary to carry out the validation of reliable technologies for this type of pathogens and evaluate their performance. This paper reports, for the first time, H. pylori reduction in a drinking water pilot plant of two slow sand filters (SSF). Inlet water was taken from a gravel filtration system of a rural water supply in Colombia and then inoculated with viable cells of H. pylori. By determining the Genomic Units (GU) through quantitative Polymerase Chain Reaction (qPCR), the concentration of GU/sample was measured. In the inlet water amplification for SSF1 and SSF2 were 5.13 × 102 ± 4.48 × 102 and 6.59 × 102 ± 7.32 × 102, respectively, while for the treated water they were 7.0 ± 5.6 and 2.05 × 101 ± 2.9 × 101 GU/sample for SSF1 and SSF2, respectively. The SSF pilot plant reached up to 3 log reduction units of H. pylori; therefore, since there is not an H. pylori contamination indicator and its periodic monitoring is financially complicated, the SSF could guarantee the drinking water quality necessity that exists in rural areas and small municipalities in developing countries, where infection rates and prevalence of this pathogen are high.