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1.
Medicine (Baltimore) ; 100(14): e24371, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33832060

RESUMEN

RATIONALE: API2-MALT1 positive gastric mucosa-associated lymphoid tissue (MALT) lymphomas are considered to have favorable prognosis. We report a case of API2-MALT1 positive gastric MALT lymphoma, treated by endoscopic submucosal dissection (ESD). PATIENT CONCERNS: A 51-year-old man underwent esophagogastroduodenoscopy (EGD) for the annual health checkup examination. DIAGNOSES: The EGD showed a reddish depressed lesion with small reddish spots in the lower gastric body. There was no endoscopic atrophy in the entire stomach and Helicobacter pylori (H. pylori) serum test was negative. Infiltration of small lymphocytes was shown in the gastric tissues obtained by the endoscopic biopsy. The fluorescence in situ hybridization using the biopsy samples confirmed the presence of genetic translocation of API2-MALT1, suggesting that the lesion is API2-MALT1 positive MALT lymphoma. INTERVENTIONS: Since endoscopic ultrasound suggested that the lesion was localized within the lamina propria mucosae, we performed ESD to achieve the en bloc resection of the lesion. OUTCOMES: Conclusive diagnosis of gastric MALT lymphoma was made based on the resected specimen. Lateral and vertical margins were negative. No lymphoma cells were detected using endoscopic biopsy after 5 years. LESSONS: Our report suggests that ESD can be considered as alternative treatment for API2-MALT1 positive gastric MALT lymphoma if the lesion was localized within the gastric mucosa.


Asunto(s)
Linfoma de Células B de la Zona Marginal/genética , Neoplasias Gástricas/genética , Translocación Genética , Helicobacter pylori/genética , Humanos , Linfoma de Células B de la Zona Marginal/patología , Linfoma de Células B de la Zona Marginal/cirugía , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica , Neoplasias Gástricas/cirugía
2.
Medicine (Baltimore) ; 100(10): e24915, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33725850

RESUMEN

RATIONALE: Antibiotic resistance poses a challenge for Helicobacter pylori eradication treatment. Current guidelines strongly recommend avoiding repeated treatments with the same antibiotic to prevent the emergence of drug resistance. However, for penicillin-allergic patients with recurrent H. pylori eradication failures, avoiding repeated treatments with the same antibiotic severely limits the choice of treatment. PATIENT CONCERNS: A 47-year-old woman with a penicillin allergy for whom 2 previous levofloxacin and bismuth-based therapies had failed. DIAGNOSIS: H. pylori infection. INTERVENTIONS: Agar dilution susceptibility testing and gene sequence analysis was performed to confirm levofloxacin susceptibility again. Therefore, we treated her with a 14-day regimen consisting of levofloxacin (500 mg once daily), furazolidone (100 mg twice daily), colloidal bismuth pectin (220 mg twice daily), and esomeprazole (20 mg twice daily). OUTCOMES: The patient was successfully treated with a third levofloxacin and bismuth-based regimen. LESSONS: Antibiotics included in previous failed therapies need not be eliminated if no antibiotic resistance is found on antimicrobial susceptibility testing.


Asunto(s)
Antibacterianos/farmacología , Gastritis/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Levofloxacino/farmacología , Antibacterianos/uso terapéutico , Bismuto/uso terapéutico , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/inmunología , Farmacorresistencia Bacteriana/genética , Quimioterapia Combinada/métodos , Esomeprazol/uso terapéutico , Femenino , Furazolidona/uso terapéutico , Mucosa Gástrica/patología , Gastritis/diagnóstico , Gastritis/microbiología , Gastritis/patología , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/genética , Helicobacter pylori/aislamiento & purificación , Humanos , Levofloxacino/uso terapéutico , Persona de Mediana Edad , Penicilinas/inmunología , Penicilinas/uso terapéutico , Recurrencia , Retratamiento/métodos , Resultado del Tratamiento
3.
Nat Commun ; 12(1): 1146, 2021 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-33608531

RESUMEN

Genetic factors are recognized to contribute to peptic ulcer disease (PUD) and other gastrointestinal diseases, such as gastro-oesophageal reflux disease (GORD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Here, genome-wide association study (GWAS) analyses based on 456,327 UK Biobank (UKB) individuals identify 8 independent and significant loci for PUD at, or near, genes MUC1, MUC6, FUT2, PSCA, ABO, CDX2, GAST and CCKBR. There are previously established roles in susceptibility to Helicobacter pylori infection, response to counteract infection-related damage, gastric acid secretion or gastrointestinal motility for these genes. Only two associations have been previously reported for duodenal ulcer, here replicated trans-ancestrally. The results highlight the role of host genetic susceptibility to infection. Post-GWAS analyses for PUD, GORD, IBS and IBD add insights into relationships between these gastrointestinal diseases and their relationships with depression, a commonly comorbid disorder.


Asunto(s)
Depresión , Enfermedades Gastrointestinales/genética , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo/métodos , Infecciones por Helicobacter/genética , Helicobacter pylori/genética , Úlcera Péptica/genética , Sistema del Grupo Sanguíneo ABO/genética , Antígenos de Neoplasias/genética , Factor de Transcripción CDX2/genética , Úlcera Duodenal , Femenino , Fucosiltransferasas/genética , Proteínas Ligadas a GPI , Galactosiltransferasas , Reflujo Gastroesofágico , Infecciones por Helicobacter/complicaciones , Humanos , Enfermedades Inflamatorias del Intestino , Masculino , Mucina-1/genética , Mucina 6/genética , Proteínas de Neoplasias , Úlcera Péptica/complicaciones
4.
J Infect Public Health ; 14(2): 271-275, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33508684

RESUMEN

BACKGROUND: Chronic infection with Helicobacter pylori, specifically cagA-positive strains, is associated with gastric cancer. Thus, measures to prevent H. pylori infection are required. This study was conducted to clarify the prevalence of H. pylori in the community to identify the infection source and comprehensively assess the risk of H. pylori infection. METHODS: We collected 90 human faecal samples and 73 environmental samples (water, vegetable, and animal faecal samples) from the residents in an area with a high incidence of gastric cancer in Japan. Polymerase chain reaction assay was performed to detect the glmM housekeeping gene and the cagA virulence gene of H. pylori. A questionnaire survey was conducted, and the responses were analyzed statistically. RESULTS: The glmM gene was detected in 18 of 90 (20%) faecal samples obtained from residents; among them, the cagA gene was detected in 33.3% (6/18), and in all who had undergone eradication therapy. H. pylori was not detected in environmental samples. However, contact with dogs (OR 3.89, 95% CI 1.15-13.15, P < 0.05) was associated with higher odds for glmM gene positivity in the questionnaire survey. CONCLUSIONS: The prevalence of H. pylori and cagA-positive strains among the residents was low. However, the study results suggest a correlation between recurrent infection and cagA-positive H. pylori strains. Although H. pylori genes were not detected in living environments, an association between contact with dogs and a glmM positive status was revealed. Further investigations targeting community-dwelling healthy people and their living environments would be required for H. pylori infection control.


Asunto(s)
Proteínas Bacterianas/genética , Heces/microbiología , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/genética , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antígenos Bacterianos/genética , Perros , Femenino , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/aislamiento & purificación , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Prevalencia
5.
Life Sci ; 267: 118921, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33358913

RESUMEN

AIMS: Helicobacter pylori (Hp) infection plays an important role in the development of gastric cancer. Hp can secrete gamma-glutamyltransferase (GGT), however, the impact of GGT of Hp on the human gastric cells is not clear. Although it has been demonstrated that ten-eleven translocation 1 (TET1) is overexpressed in gastric cancer, the relationship between the GGT of Hp and TET1 has not been studied. The aim of this study was to explore the relationship between GGT and TET1, and the role of TET1 in the development of gastric cancer induced by Hp was also explored. MATERIALS AND METHODS: The correlation between TET1 and prognosis of gastric adenoma cancer was analyzed by bioinformatics. The GGT gene of Hp26695 was knocked out by electroporation with plasmid to construct the GGT knockout strain of Hp (Hp-KS-1). The shTET1 lentivirus transfected GES-1, MGC-803 and SGC-7901 cell lines were constructed. The biological characteristics of the three kind of cells were detected. KEY FINDINGS: TET1 was overexpressed in gastric tissues of Hp infected patients and mice. Bioinformatics analysis showed that in patients with gastric cancer, higher TET1 expression would result in poorer prognosis. The GGT gene of Hp can lead to overexpression of TET1 in GES-1, MGC-803 and SGC-7901 cells, along with the activation of Wnt/ß-catenin signaling pathway, and then promoting tumorigenesis. After silencing TET1, the Wnt/ß-catenin signaling pathway which was activated by GGT of Hp was inhibited. SIGNIFICANCE: GGT of Helicobacter pylori can promote gastric carcinogenesis by activating Wnt/ß-catenin signaling pathway trough up-regulating TET1.


Asunto(s)
Infecciones por Helicobacter/microbiología , Helicobacter pylori/enzimología , Helicobacter pylori/genética , Oxigenasas de Función Mixta/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Neoplasias Gástricas/microbiología , Vía de Señalización Wnt , gamma-Glutamiltransferasa/genética , Pólipos Adenomatosos/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Transformación Celular Neoplásica , Mucosa Gástrica/metabolismo , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/patología , Helicobacter pylori/metabolismo , Humanos , Masculino , Ratones , Ratones Desnudos , Oxigenasas de Función Mixta/genética , Proteínas Proto-Oncogénicas/genética , Neoplasias Gástricas/metabolismo , Activación Transcripcional , beta Catenina/metabolismo , gamma-Glutamiltransferasa/metabolismo
6.
PLoS Pathog ; 16(12): e1008686, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33370399

RESUMEN

Helicobacter pylori chronically infects the stomach of approximately half of the world's population. Manifestation of clinical diseases associated with H. pylori infection, including cancer, is driven by strain properties and host responses; and as chronic infection persists, both are subject to change. Previous studies have documented frequent and extensive within-host bacterial genetic variation. To define how within-host diversity contributes to phenotypes related to H. pylori pathogenesis, this project leverages a collection of 39 clinical isolates acquired prospectively from a single subject at two time points and from multiple gastric sites. During the six years separating collection of these isolates, this individual, initially harboring a duodenal ulcer, progressed to gastric atrophy and concomitant loss of acid secretion. Whole genome sequence analysis identified 1,767 unique single nucleotide polymorphisms (SNPs) across isolates and a nucleotide substitution rate of 1.3x10-4 substitutions/site/year. Gene ontology analysis identified cell envelope genes among the genes with excess accumulation of nonsynonymous SNPs (nSNPs). A maximum likelihood tree based on genetic similarity clusters isolates from each time point separately. Within time points, there is segregation of subgroups with phenotypic differences in bacterial morphology, ability to induce inflammatory cytokines, and mouse colonization. Higher inflammatory cytokine induction in recent isolates maps to shared polymorphisms in the Cag PAI protein, CagY, while rod morphology in a subgroup of recent isolates mapped to eight mutations in three distinct helical cell shape determining (csd) genes. The presence of subgroups with unique genetic and phenotypic properties suggest complex selective forces and multiple niches within the stomach during chronic infection.


Asunto(s)
Úlcera Duodenal/microbiología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/genética , Helicobacter pylori/genética , Gastropatías/microbiología , Animales , Atrofia/microbiología , Enfermedad Crónica , Ácido Gástrico , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Fenotipo , Polimorfismo de Nucleótido Simple , Gastropatías/patología
7.
Rev. Assoc. Med. Bras. (1992) ; 66(11): 1509-1514, Nov. 2020. tab, graf
Artículo en Inglés | LILACS, Sec. Est. Saúde SP | ID: biblio-1143632

RESUMEN

SUMMARY INTRODUCTION: Nearly 73% of the Chilean population is infected with Helicobacter pylori (H. pylori), a factor predisposing for gastric cancer. Recent studies have demonstrated the presence of this pathogen within yeasts, suggesting that this fact can directly influence the failure of a treatment, transmission, and reinfection. AIM: To detect the presence of H. pylori inside oral yeasts isolated from students of the University of Concepción (Chile). METHODS: 72 samples, obtained from the oral cavity using cotton swabs were incubated in YPD broth for 48h at 37°C and posteriorly seeded in Sabouraud Dextrose agar plus chloramphenicol at the same temperature and for the same time. Yeasts isolated were observed microscopically (wet mounting and Gram-stained) and identified using microbiological techniques. Intracellular H. pylori detection was performed by the amplification of 16S rDNA by PCR. RESULTS: Oral yeasts were detected in 24 samples (33.3%), being C. albicans (79.2%) the most frequent species, followed by C. dubliniensis (12.4%), C. krusei (4.2%), and C. tropicalis (4.2%). When analyzed by PCR, 15 of the 24 oral yeasts 62.5 % were positive for H. pylori 16S rDNA. From the 15 individuals positive for yeast harboring H. pylori, 81% of them reported stomach discomfort, and the presence of the bacteria was diagnosed at some moment in 20% of them. CONCLUSION: The intracellular presence of the H. pylori in oral yeasts suggests an endosymbiotic relationship of these microorganisms, which could favor H. pylori transmission and reinfection in the gastrointestinal tract.


RESUMO INTRODUÇÃO: Quase 73% da população chilena estão infectadas pelo Helicobacter pylori (H. pylori), fator predisponente ao câncer gástrico. Estudos recentes demonstraram a presença desse patógeno em leveduras, sugerindo que esse fato pode influenciar diretamente a falha de um tratamento, transmissão e reinfecção. OBJETIVO: Detectar a presença de H. pylori em leveduras orais isoladas de estudantes da Universidade de Concepción (Chile). MÉTODOS: 72 amostras, obtidas da cavidade oral utilizando cotonetes, foram incubadas em caldo YPD por 48h a 37°C e posteriormente sementes em ágar Sabouraud Dextrose mais cloranfenicol na mesma temperatura e ao mesmo tempo. Leveduras isoladas foram observadas microscopicamente (montagem úmida e corada por Gram) e identificadas utilizando técnicas microbiológicas. A detecção intracelular de H. pylori foi realizada pela amplificação do 16S rDNA por PCR. RESULTADOS: Leveduras orais foram detectadas em 24 amostras (33,3%), sendo C. albicans (79,2%), a espécie mais frequente seguida por C. dubliniensis (12,4%), C. krusei (4,2%) e C. tropicalis (4,2 %) Quando analisadas por PCR, 15 das 24 leveduras orais 62,5% foram positivas para o H. pylori 16S rDNA. Dos 15 indivíduos positivos para leveduras que abrigam H. pylori, 81% deles relataram desconforto estomacal e a presença da bactéria foi diagnosticada em algum momento em 20% deles. CONCLUSÃO: A presença intracelular do H. pylori em leveduras orais sugere uma relação endossimbiótica desses microrganismos, o que poderia favorecer a transmissão e a reinfecção do H. pylori no trato gastrointestinal.


Asunto(s)
Humanos , Helicobacter pylori/genética , Infecciones por Helicobacter , Estudiantes , Universidades , ADN Bacteriano , Chile/epidemiología
8.
Mol Cell ; 80(2): 210-226.e7, 2020 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-33002424

RESUMEN

Many bacterial pathogens regulate their virulence genes via phase variation, whereby length-variable simple sequence repeats control the transcription or coding potential of those genes. Here, we have exploited this relationship between DNA structure and physiological function to discover a globally acting small RNA (sRNA) regulator of virulence in the gastric pathogen Helicobacter pylori. Our study reports the first sRNA whose expression is affected by a variable thymine (T) stretch in its promoter. We show the sRNA post-transcriptionally represses multiple major pathogenicity factors of H. pylori, including CagA and VacA, by base pairing to their mRNAs. We further demonstrate transcription of the sRNA is regulated by the nickel-responsive transcriptional regulator NikR (thus named NikS for nickel-regulated sRNA), thereby linking virulence factor regulation to nickel concentrations. Using in-vitro infection experiments, we demonstrate NikS affects host cell internalization and epithelial barrier disruption. Together, our results show NikS is a phase-variable, post-transcriptional global regulator of virulence properties in H. pylori.


Asunto(s)
Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , ARN Bacteriano/genética , Secuencias Repetitivas de Ácidos Nucleicos/genética , Factores de Virulencia/metabolismo , Proteínas Bacterianas/metabolismo , Secuencia de Bases , Recuento de Colonia Microbiana , Endocitosis/efectos de los fármacos , Eliminación de Gen , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Helicobacter pylori/efectos de los fármacos , Interacciones Huésped-Patógeno/efectos de los fármacos , Níquel/farmacología , Fenotipo , Regiones Promotoras Genéticas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transcripción Genética/efectos de los fármacos
9.
Mol Cell ; 80(2): 175-177, 2020 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-33065017

RESUMEN

Eisenbart et al. (2020) find an SSR-associated sRNA, NikS, that is subject to variable repeat-controlled expression. NikS regulates H. pylori virulence by post-transcriptionally repressing pathogenicity factors, including CagA and VacA, via base-pairing to their mRNAs.


Asunto(s)
Helicobacter pylori , Factores de Virulencia , ADN , Regulación Bacteriana de la Expresión Génica , Helicobacter pylori/genética , ARN Bacteriano/genética , Virulencia/genética
10.
Acta Gastroenterol Belg ; 83(3): 385-392, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33094584

RESUMEN

INTRODUCTION: As a component of the cag T4SS, the cagL gene is involved in the translocation of CagA into host cells and is essential for the formation of cag PAI-associated pili between H. pylori and gastric epithelial cells. AIM: We aimed to investigate the clinical association of the cagL gene with other virulence factors (VacA, CagA, EPIYA-C, and BabA protein) of H. pylori strains isolated from GC, duodenal ulcer (DU), and non-ulcer dyspepsia (NUD) cases. METHODS: The patient group (PG), including 47 patients (22 GC and 25 DU) and a 25 control group (CG= NUD) were included. Amplification of the H. pylori cagL, cagA, vacA, and babA2 genes and typing of EPIYA motifs were performed by PCR methods. RESULTS: Sixty-one (84.7%) H. pylori strains were detected with cagL (93.6% in SG, 68% in CG). We detected a significant difference between SG and CG for the presence of cagL (p=0.012) but no statistical comparison was done for (≥2) EPIYA-C repeats In the comparison of H. pylori strains with cagA/vacAs1m1 and cagA/ vacAs1m2 and babA2 for the presence of cagL, we could not detect a significant difference (p=1). CONCLUSION: We detected a significant difference between groups for the presence of cagL genotype (p=0.012). The vacAs1m1 (OR: 2.829), genotypes increased the GC and DU risk by 2.8 times, while multiple (≥2) EPIYA-C repeats incresed the GC and DU risk by 3.524 times. Gender (to be female) (OR: 0.454) decreased the GC and DU risk by inversly decreased in the multivariate analysis.


Asunto(s)
Neoplasias Duodenales , Úlcera Duodenal , Dispepsia , Infecciones por Helicobacter , Helicobacter pylori , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Neoplasias Duodenales/genética , Neoplasias Duodenales/microbiología , Úlcera Duodenal/genética , Úlcera Duodenal/microbiología , Dispepsia/genética , Dispepsia/microbiología , Femenino , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/genética , Humanos , Masculino , Úlcera
11.
Anticancer Res ; 40(11): 6387-6398, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33109577

RESUMEN

BACKGROUND/AIM: Helicobacter pylori (Hp) infection affects a substantial proportion of the world population and is a major risk factor of gastric cancer (GC). The caveats of common Hp-tests can be evaded by a serological biomarker test (GastroPanel®, Biohit Oyj, Helsinki), the most comprehensive Hp-test on the market. The clinical validation of Helicobacter pylori IgG ELISA of the new-generation GastroPanel® test is reported. The aim of the study is to validate the clinical performance of the Helicobacter pylori IgG ELISA test in diagnosis of biopsy-confirmed Hp-infection in gastroscopy referral patients. PATIENTS AND METHODS: A cohort of 101 patients (mean age=50.1 years) referred for gastroscopy at the outpatient Department of Gastroenterology (SM Clinic, St. Petersburg) were examined by two test versions to validate the new-generation GastroPanel®. All patients were examined by gastroscopy and biopsies, which were stained with Giemsa for specific identification of Hp in the antrum (A) and corpus (C). RESULTS: Biopsy-confirmed Hp-infection was found in 64% of patients, most often confined to antrum. The overall agreement between Hp IgG ELISA and gastric biopsies in Hp-detection was 91% (95%CI=84.1-95.8%). Hp IgG ELISA diagnosed biopsy-confirmed Hp (A&C) with sensitivity (SE) of 92.3%, specificity (SP) of 88.6%, positive predictive value (PPV) of 93.8% and negative predictive value (NPV) of 86.1%, with AUC=0.904 (95%CI=0.842-0.967). In ROC analysis for Hp detection (A&C), Hp IgG ELISA shows AUC=0.978 (95%CI=0.956-1.000). CONCLUSION: The Hp IgG ELISA test successfully concludes the clinical validation process of the new-generation GastroPanel® test, which retains the unrivalled diagnostic performance of all its four biomarkers, extensively documented for the first-generation test in different clinical settings.


Asunto(s)
Anticuerpos Antibacterianos/aislamiento & purificación , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/aislamiento & purificación , Inmunoglobulina G/aislamiento & purificación , Adolescente , Adulto , Anticuerpos Antibacterianos/genética , Anticuerpos Antibacterianos/inmunología , Biopsia , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Gastrinas/genética , Gastrinas/aislamiento & purificación , Gastritis Atrófica/diagnóstico , Gastritis Atrófica/genética , Gastritis Atrófica/microbiología , Gastritis Atrófica/patología , Gastroscopía/métodos , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Humanos , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Pepsinógeno A/genética , Pepsinógeno A/aislamiento & purificación , Pepsinógeno C/genética , Pepsinógeno C/aislamiento & purificación , Derivación y Consulta , Estómago/microbiología , Estómago/patología , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Adulto Joven
13.
Medicine (Baltimore) ; 99(32): e20761, 2020 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-32769862

RESUMEN

The regimens containing levofloxacin (LVX) have been recommended as an alternate to standard triple therapy to treat Helicobacter pylori infections and H pylori mixed infection always lead to H pylori chronic infection. Although the molecular mechanism of LVX resistance with gyrA gene mutation has been clearly understood in H pylori, other genes involved in antibiotic resistance remain unclear. Efflux pump plays an important role in clinically relevant multidrug resistance. Furthermore, the relationship between the strains with different LVX level-resistances from individuals is also unknown.Helicobacter pylori monoclonal strains were isolated from patients with eradication failure. E test was used to detect the minimal inhibitory concentration of LVX. One lower-level LVX-resistant clone and 2 higher-level LVX-resistant clones from the same patient were selected to sequence the complete genomes. Single-nucleotide variants (SNVs) and mutations were extracted and analyzed from gryA and resistance-nodulation-division family efflux genes.Two clones with higher-level resistance had the mutation pattern of Asn87Lys and one lower-level LVX-resistant clone had an Asp91Asn mutation. Compared to clones with higher-level resistance, the higher genetic variations were found in genes belonging to the resistance-nodulation-division family in H pylori strains with lower-level resistance to LVX. There were significantly more SNVs of Hp0970 (hefE) and Hp1329 (hefI) in the lower-level LVX-resistant clone than those in the higher-level LVX-resistant clones (P = .044).The mutation pattern of the Asn87Lys of the gyrA gene confers a higher resistance to LVX than that of the Asp91Asn in H pylori. Increase in the number of SNVs of the Hp0970 (hefE) and Hp1329 (hefI) genes change the resistance to LVX. Twelve mutations verified by Sanger sequencing in Hp0970 (hefE) and Hp1329 (hefI) may decrease resistant levels to LVX.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Infecciones por Helicobacter/microbiología , Helicobacter pylori/genética , Levofloxacino/farmacología , Mutación/genética , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/aislamiento & purificación , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos
14.
Eur J Clin Microbiol Infect Dis ; 39(10): 1821-1830, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32557327

RESUMEN

Helicobacter pylori (H. pylori) infection is associated with some gastric diseases, such as gastritis, peptic ulcer, and gastric cancer. CagA and VacA are known virulence factors of H. pylori, which play a vital role in severe clinical outcomes. Additionally, the expression of outer membrane proteins (OMPs) helps H. pylori attach to gastric epithelial cells at the primary stage and increases the virulence of H. pylori. In this review, we have summarized the paralogs of H. pylori OMPs, their genomic loci, and the different receptors of OMPs identified so far. We focused on five OMPs, BabA (HopS), SabA (HopP), OipA (HopH), HopQ, and HopZ, and one family of OMPs: Hom. We highlight the coexpression of OMPs with other virulence factors and their relationship with clinical outcomes. In conclusion, OMPs are closely related to the pathogenic processes of adhesion, colonization, persistent infection, and severe clinical consequences. They are potential targets for the prevention and treatment of H. pylori-related diseases.


Asunto(s)
Proteínas de la Membrana Bacteriana Externa/genética , Proteínas de la Membrana Bacteriana Externa/metabolismo , Infecciones por Helicobacter/microbiología , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Factores de Virulencia/metabolismo , Células Epiteliales/microbiología , Expresión Génica , Humanos , Factores de Virulencia/genética
15.
Environ Pollut ; 264: 114768, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32434114

RESUMEN

Wastewater has become one of the most important and least expensive water for the agriculture sector, as well as an alternative to the overexploitation of water resources. However, inappropriate treatment before its reuse can result in a negative impact on the environment, such as the presence of pathogens. This poses an increased risk for environmental safety, which can subsequently lead to an increased risk for human health. Among all the emerging wastewater pathogens, bacteria of the genus Helicobacter are some of the most disturbing ones, since they are directly related to gastric illness and hepatobiliary and gastric cancer. Therefore, the aim of this study was to determine the presence of potentially pathogenic Helicobacter spp. in treated wastewater intended for irrigation. We used a next generation sequencing approach, based on Illumina sequencing in combination with culture and other molecular techniques (qPCR, FISH and DVC-FISH), to analyze 16 wastewater samples, with and without an enrichment step. By culture, one of the direct samples was positive for H. pylori. FISH and DVC-FISH techniques allowed for detecting viable Helicobacter spp., including H. pylori, in seven out of eight samples of wastewater from the tertiary effluents, while qPCR analysis yielded only three positive results. When wastewater microbiome was analyzed, Helicobacter genus was detected in 7 samples. The different molecular techniques used in the present study provided evidence, for the first time, of the presence of species belonging to the genus Helicobacter such as H. pylori, H. hepaticus, H. pullorum and H. suis in wastewater samples, even after disinfection treatment.


Asunto(s)
Helicobacter pylori/genética , Helicobacter , Humanos , Hibridación Fluorescente in Situ , Reacción en Cadena en Tiempo Real de la Polimerasa , Aguas Residuales
16.
Postgrad Med ; 132(6): 512-520, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32281451

RESUMEN

Objectives: Helicobacter pylori (H. pylori) infection caused by antibiotic-resistant strains represents a major public health threat that aggressively promotes gastric cancer progression. Antibiotic resistance evaluation is immensely important to counteract its emergence. Here we merely determine the prevalence of antibiotic resistance in H. pylori isolates and its correlation with cagA motifs and the homB gene. Methods: The antibiotic resistance pattern was investigated on 128 H. pylori isolated strains utilizing the disk diffusion method and study the correlation between it and the presence of pathogenic genes, cagA EPIYA motifs and homB gene, were accurately detected using the PCR. Results: The resistance rates to four antibiotics were 70.1% for metronidazole, 35.5% for amoxicillin, 7.2% for clarithromycin and 8.2% for tetracycline. Resistance phenotypes were separated into two groups, single resistance (63.2%) and multi-resistance (12.5%). The prevalence of cagA-ABCC resistant strains and homB+ resistant strains was significantly higher in cancer (p = 0.04 and p = 0.01, respectively) than those of other diseases. The prevalence of cagA-homB + resistance strains was 21.8% and had a significant correlation with PUD. A significant relationship was observed between amoxicillin resistant rate with ABC-homB (p = 0.0006). Conclusion: The Resistance rate to selected antibiotics in Shiraz is higher than years ago. The presence of cagA-homB + is associated with antibiotic resistance and also homB can be used as a marker to antibiotic resistance status prediction in H. pylori isolated in this area.


Asunto(s)
Antibacterianos , Antígenos Bacterianos/genética , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas Bacterianas/genética , Farmacorresistencia Microbiana/genética , Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Adulto , Antibacterianos/clasificación , Antibacterianos/farmacología , Femenino , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/genética , Helicobacter pylori/aislamiento & purificación , Humanos , Irán/epidemiología , Masculino , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología
17.
J Nanobiotechnology ; 18(1): 63, 2020 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-32316990

RESUMEN

BACKGROUND: Helicobacter pylori (H. pylori) infect more than half of the world population, and they cause different serious diseases such as gastric carcinomas. This study aims to design a vaccine on the basis of cagW against H. pylori infection. After pcDNA3.1 (+)-cagW-CS-NPs complex is produced, it will be administered into the muscles of healthy BALB/c mice in order to study the effect of this DNA vaccine on the interleukin status of mice, representing its effect on the immune system. After that, the results will be compared with the control groups comprising the administration of cagW-pCDNA3.1 (+) vaccine, the administration of chitosan and the administration of PBS in the muscles of mice. METHODS: The cagW gene of H. pylori was amplified by employing PCR, whose product was then cloned into the pcDNA3.1 (+) vector, and this cloning was confirmed by PCR and BamHI/EcoRV restriction enzyme digestion. CagW gene DNA vaccine was encapsulated in chitosan nanoparticles (pcDNA3.1 (+)-cagW-CS-NPs) using a complex coacervation method. The stability and in vitro expression of chitosan nanoparticles were studied by DNase I digestion and transfection, and the immune responses elicited in specific pathogen-free (SPF) mice by the pcDNA3.1 (+)-cagW-CS-NPs were evaluated. Apart from that, the protective potential pcDNA3.1 (+)-cagW-CS-NPs was evaluated by challenging with H. pylori. RESULTS: The pcDNA3.1 (+)-cagW-CS-NPs comprises cagW gene of H. pylori that is encapsulated in chitosan nanoparticles, produced with good morphology, high stability, a mean diameter of 117.7 nm, and a zeta potential of + 5.64 mV. Moreover, it was confirmed that chitosan encapsulation protects the DNA plasmid from DNase I digestion, and the immunofluorescence assay showed that the cagW gene could express in HDF cells and maintain good bioactivity at the same time. In comparison to the mice immunized with the control plasmid, in vivo immunization revealed that mice immunized with pcDNA3.1 (+)-cagW-NPs showed better immune responses and prolonged release of the plasmid DNA. CONCLUSIONS: This research proves chitosan-DNA nanoparticles as potent immunization candidates against H. pylori infection and paves the way for further developments in novel vaccines encapsulated in chitosan nanoparticles.


Asunto(s)
Proteínas Bacterianas/genética , Infecciones por Helicobacter/prevención & control , Vacunas de ADN/inmunología , Factores de Virulencia/genética , Animales , Anticuerpos Antibacterianos/sangre , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Quitosano/química , Modelos Animales de Enfermedad , Infecciones por Helicobacter/patología , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Inmunidad Celular , Interferón gamma/metabolismo , Ratones , Ratones Endogámicos BALB C , Nanopartículas/química , Plásmidos/genética , Plásmidos/metabolismo , Transfección/métodos
18.
Sci Rep ; 10(1): 6570, 2020 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-32300197

RESUMEN

Helicobacter pylori (HP) colonizes the human stomach and induces acute gastritis, peptic ulcer disease, atrophic gastritis, and gastric adenocarcinoma. Increased virulence in HP isolates derives from harboring the cag (cytotoxin-associated genes) pathogenicity island (cagPAI). We analyzed the microvariants in cagPAI genes with the hypothesis that they may play an important role in determining HP virulence. We tested DNAs from cagA positive patients HP isolates; a total of 74 patients with chronic gastritis (CG, N = 37), intestinal metaplasia (IM, N = 21) or gastric cancer (GC, N = 16) from Mexico and Colombia. We selected 520 non-synonymous variants with at least 7.5% frequency in the original sequence outputs or with a minimum of 5 isolates with minor allele. After adjustment for multiple comparisons, no variants were statistically significantly associated with IM or GC. However, 19 non-synonymous showed conventional P-values < 0.05 comparing the frequency of the alleles between the isolates from subjects with gastritis and isolates from subjects with IM or GC; 12 of these showed a significant correlation with the severity of the disease. The present study revealed that several cagPAI genes from Latin American Western HP strains contains a number of non-synonymous variants in relatively high frequencies which could influence on the clinical outcome. However, none of the associations remained statistically significant after adjustment for multiple comparison.


Asunto(s)
Progresión de la Enfermedad , Variación Genética , Islas Genómicas/genética , Helicobacter pylori/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiología , Gastritis/microbiología , Genoma Bacteriano , Humanos , América Latina , Metaplasia , Motivos de Nucleótidos/genética , Polimorfismo Genético , Análisis de Secuencia de ADN , Neoplasias Gástricas/patología
19.
Braz. j. otorhinolaryngol. (Impr.) ; 86(2): 217-221, March-Apr. 2020. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1132581

RESUMEN

Abstract Introduction: It is proposed that Helicobacter pylori can be responsible for the development of otitis media with effusion. Objective: The aim of this study is to investigate the prevalence of H. pylori in the adenoid tissue and fluid of the middle ear in patients who suffer from adenoid hyperplasia and otitis media with effusion in comparison with those who suffer from adenoid hyperplasia without otitis media with effusion. Methods: This is a case-control study that was carried out in 50 children of age 2-7 years old who were admitted with adenoid hyperplasia. Patients were divided into case and control groups. The study group included 25 patients with adenoid hyperplasia and otitis media with effusion and the control group included 25 patients with adenoid hyperplasia without otitis media with effusion. The patients in both groups underwent surgical adenoidectomy. For the case group we carried out myringotomy and placement of tympanostomy tube, and fluid samples were collected under sterile conditions. The samples were sent to the laboratory for polymerase chain reactions. Results: In the case group H. pylori was found to be positive in 18 samples of the middle ear fluid (70%) and in 1 polymerase chain reaction adenoid tissue sample (4%). In the control group H. pylori was positive in 3 samples of adenoid tissues (12%). There was no gender difference. Conclusion: H. pylori is one of the important bacteria that plays a role in the pathogenesis of otitis media with effusion. Whether adenoid tissue may be a reservoir for H. Pylori is unclear.


Resumo Introdução: Propõe-se que o Helicobacter pylori possa ser responsável pelo desenvolvimento de otite média com efusão. Objetivo: Investigar a prevalência de H. pylori no tecido adenoideano e no fluido da orelha média em pacientes com hiperplasia de adenoide e otite média com efusão em comparação àqueles com hiperplasia de adenoide sem otite média com efusão. Método: Este é um estudo de caso-controle feito em 50 crianças de 2 a 7 anos, com sinais e sintomas de hiperplasia de adenoide. Os pacientes foram divididos em grupo de estudo e grupo controle. O grupo de estudo incluiu 25 pacientes com hiperplasia de adenoide e otite média com efusão e o grupo controle incluiu 25 pacientes com hiperplasia de adenoide sem otite média com efusão. Os pacientes dos dois grupos foram submetidos a adenoidectomia e, no grupo de estudo, realizou-se também miringotomia com colocação de tubo de ventilação e amostras de fluidos foram coletadas sob condições estéreis. As amostras foram enviadas para o laboratório, para investigação por reação de polimerase em cadeia. Resultados: No grupo de estudo, houve positividade para H. pylori em 18 amostras do fluido de orelha média (70%) e uma amostra de tecido adenoideano foi positiva na reação de polimerase em cadeia (4%). No grupo controle, houve positividade para H. pylori em 3 amostras de tecido adenoideano (12%). Não houve diferença entre os gêneros. Conclusão: H. pylori é uma das bactérias importantes que desempenham um papel na patogênese da otite médica com efusão. Se o tecido adenoideano pode ou não representar um reservatório para H. pylori ainda necessita ser esclarecido.


Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Otitis Media con Derrame/microbiología , ADN Bacteriano/genética , Helicobacter pylori/genética , Infecciones por Helicobacter/diagnóstico , Estudios de Casos y Controles , Reacción en Cadena de la Polimerasa , Helicobacter pylori/aislamiento & purificación
20.
Biochem Biophys Res Commun ; 525(3): 806-811, 2020 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-32164943

RESUMEN

Helicobacter pylori, a pathogenic bacterium that colonizes in the human stomach, harbors DNA repair genes to counter the gastric environment during chronic infection. In addition, H. pylori adapts to the host environment by undergoing antigenic phase variation caused by genomic mutations. The emergence of mutations in nucleotide sequences is one of the major factors underlying drug resistance and genetic diversity in bacteria. However, it is not clear how DNA repair genes contribute to driving the genetic change of H. pylori during chronic infection. To elucidate the physiological roles of DNA repair genes, we generated DNA repair-deficient strains of H. pylori (ΔuvrA, ΔuvrB, ΔruvA, Δnth, ΔmutY, ΔmutS, and Δung). We performed susceptibility testing to rifampicin in vitro and found that ΔmutY exhibited the highest mutation frequency among the mutants. The number of bacteria colonizing the stomach was significantly lower with ΔmutY strain compared with wild-type strains in a Mongolian gerbil model of H. pylori infection. Furthermore, we performed a genomic sequence analysis of the strains isolated from the Mongolian gerbil stomachs eight weeks after infection. We found that the isolated ΔmutY strains exhibited a high frequency of spontaneous G:C to T:A mutations. However, the frequency of phase variations in the ΔmutY strain was almost similar to the wild-type strain. These results suggest that MutY may play a role in modes of gastric environmental adaptation distinct from phase variation.


Asunto(s)
Adaptación Fisiológica , ADN Glicosilasas/genética , Helicobacter pylori/genética , Mutación/genética , Estómago/microbiología , Animales , Proteínas Bacterianas/genética , Reparación del ADN/genética , Modelos Animales de Enfermedad , Gerbillinae , Infecciones por Helicobacter/microbiología , Helicobacter pylori/crecimiento & desarrollo , Tasa de Mutación , FN-kappa B/metabolismo
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