RESUMO
Helicobacter pylori is a major cause of gastrointestinal disorders such as chronic gastritis, peptic ulcers, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. It is estimated that around half of the world's population is infected with this pathogen, with underdeveloped countries reporting the highest frequencies. The genes cagA, cagM, vacA, and oipA are some of the most important virulence factors of H. pylori; however, there are no recent studies from Recife-PE demonstrating their frequency, and their relationship with severe gastric modifications. This work aims to use qualitative PCR to detect the virulence genes cagA, cagM, vacA, and oipA in H. pylori isolates obtained from patients in a public hospital in Recife (PE). We collected samples from the stomach's body and antrum of 147 patients, from which 71 (48%) tested positive for H. pylori. Among positive samples, the most frequently infected gender was female (44/71, 62%), and the most frequently infected age group was those above the age of 46 (31/71, 44%). Histological examination of H. pylori-positive samples revealed alterations other than chronic gastritis, including metaplasia and atrophy. The frequency of cagA, cagM, and oipA genes were identified in 84%, 56%, and 69% of the samples tested, respectively, as well as the vacA-s1m1 allelic combination (77%). However, there was no statistically significant variation in the occurrence of these genes, therefore they cannot be considered unique markers of severity in our setting. New research with larger samples and investigations of other genetic markers can aid uncover local risk factors and lead to a better understanding of H. pylori's pathogenesis.
Assuntos
Antígenos de Bactérias , Proteínas de Bactérias , Infecções por Helicobacter , Helicobacter pylori , Fatores de Virulência , Humanos , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/patogenicidade , Helicobacter pylori/classificação , Proteínas de Bactérias/genética , Feminino , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto , Brasil/epidemiologia , Fatores de Virulência/genética , Antígenos de Bactérias/genética , Idoso , Adulto Jovem , Prevalência , Adolescente , Idoso de 80 Anos ou mais , Proteínas da Membrana Bacteriana ExternaRESUMO
Helicobacter pylori is the most common cause of gastroduodenal diseases. The concept that cagA-positive H. pylori is a risk factor for gastric cancer appears to be true only for H. pylori strains from Western countries. Other virulent genes may have a synergistic interaction with cagA during pathogenesis. This study aims to investigate H. pylori cagA, vacA, and iceA prevalence, genotypes, and their association to clinical outcomes in Vietnamese patients. The cagA status and vacA and iceA genotypes were determined using the PCR technique on DNA extracted from gastric biopsies of 141 patients with gastroduodenal diseases. After performing molecular analysis for cagA, vacA, and iceA genes, samples with mixed H. pylori strains, positivity, or negativity for both cagA and cagPAI-empty site, or unidentified genotypes were excluded. Finally, 107 samples were examined. The presence of the cagA, vacA, and iceA genes were detected in 77.6%, 100%, and 80.4% of cases, respectively. Notably, cagA( +) with EPIYA-ABD, vacA s1i1m1, vacA s1i1m2, iceA1, and iceA2 accounted for 73.8%, 44.9%, 33.6%, 48.6%, and 31.8% of cases, respectively. Four iceA2 subtypes (24-aa, 59-aa, 94-aa, and 129-aa variants) were found, with the 59-aa variant the most prevalent (70.6%). The cagA( +)/vacAs1i1m1/iceA1 and cagA( +)/vacAs1i1m2/iceA1 combinations were found in 26.2% and 25.1% of cases, respectively. A multivariable logistic regression analysis was performed, after adjusting for age and gender, with the gastritis group was used as a reference control. Statistically significant associations were found between the vacA s1i1m2 genotype, the iceA1 variant, and the cagA( +)/vacAs1i1m2/iceA1 combination and gastric cancer; the adjusted ORs were estimated as 18.02 (95% CI: 3.39-95.81), 4.09 (95% CI: 1.1-15.08), and 16.19 (95% CI: 3.42-76.66), respectively. Interestingly, for the first time, our study found that vacA s1i1m2, but not vacA s1i1m1, was a risk factor for gastric cancer. This study illustrates the genetic diversity of the H. pylori cagA, vacA, and iceA genes across geographical regions and contributes to understanding the importance of these genotypes for clinical outcomes.
Assuntos
Antígenos de Bactérias , Proteínas de Bactérias , Genótipo , Infecções por Helicobacter , Helicobacter pylori , Humanos , Proteínas de Bactérias/genética , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/classificação , Helicobacter pylori/patogenicidade , Vietnã/epidemiologia , Antígenos de Bactérias/genética , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/epidemiologia , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Proteínas da Membrana Bacteriana Externa/genética , Idoso , Adulto Jovem , Prevalência , Fatores de Virulência/genéticaRESUMO
Helicobacter pylori is the etiological agent of chronic gastritis, peptic ulcer, and gastric cancer. The duodenal ulcer-promoting gene dupA, which is located in the plasticity region of the H. pylori genome, is homologous to the virB gene which encodes a type IV secretion protein in Agrobacterium tumefaciens. Studies have shown associations between H. pylori dupA-positive strains and gastroduodenal diseases. However, whether dupA acts as a risk factor or protective factor in these diseases remains unclear. Therefore, in this study, we aimed to verify the presence of the dupA gene in infectious H. pylori strains in the Brazilian mid-west and to investigate its association with the clinical outcomes of patients with dyspepsia. Additionally, the phylogenetic origin of the strains was determined. Gastric biopsies from 117 patients with dyspepsia were analyzed using histological and molecular techniques. The hpx gene (16S rRNA) was used to screen for H. pylori infection, and positive samples were then subjected to dupA gene detection and sequencing. The estimated prevalence of H. pylori infection was 64.1%, with the dupA gene being detected in a high proportion of infectious strains (70.7%). Furthermore, a risk analysis revealed that for women, a dupA-positive H. pylori infection increased the chance of developing gastritis by twofold. The partial dupA sequences from isolated infectious strains in this work are similar to those of strains isolated in westerns countries. This study provides useful insights for understanding the role of the H. pylori dupA gene in disease development.
Assuntos
Proteínas de Bactérias , Infecções por Helicobacter , Helicobacter pylori , Fatores de Virulência , Proteínas de Bactérias/genética , Brasil/epidemiologia , Dispepsia/complicações , Dispepsia/epidemiologia , Dispepsia/microbiologia , Feminino , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/classificação , Helicobacter pylori/genética , Helicobacter pylori/patogenicidade , Humanos , Masculino , Filogenia , Fatores de Proteção , RNA Ribossômico 16S/genética , Fatores de Risco , Fatores de Virulência/genéticaRESUMO
Aim:Helicobacter pylori is usually detected based on hematoxylin-eosin (H-E) features, but, immunohistochemistry (IHC) and real-time PCR (RT-PCR) are more precise in chronic-gastritis. We evaluated the relevance of these tests in Peruvian gastric cancer samples. Materials & methods: We performed and evaluated H-E, IHC staining and RT-PCR in 288 gastric tumors. Slides were independently evaluated by three pathologists. Results:H. pylori was detected in 167/287 through H-E, 140/288 through IHC and 175/288 through RT-PCR, and positive-status were associated (p < 0.001). H. pylori detection by H-E had a good concordance with IHC (kappa index = 0.632) but poor with RT-PCR (kappa index = 0.317). Higher median gene-copies were found in high H. pylori density through H-E or IHC (p < 0.001). Conclusion: H-E evaluation is accurate in gastric cancer, and IHC and RT-PCR can complement its results.
Assuntos
Helicobacter pylori/isolamento & purificação , Técnicas Histológicas/métodos , Imuno-Histoquímica/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Helicobacter pylori/classificação , Helicobacter pylori/genética , Humanos , MasculinoRESUMO
There is a lack of evidence of genetic variation in the Helicobacter pylori cag-PAI in Thailand, a region with the low incidence of gastric cancer. To clarify this issue, variation in the H. pylori cag-PAI in strains detected in Thailand was characterized and simultaneously compared with strains isolated from a high-risk population in Korea. The presence of ten gene clusters within cag-PAI (cagA, cagE, cagG, cagH, cagL, cagM, cagT, orf13, virB11, and orf10) and IS605 was characterized in H. pylori strains detected from these two countries. The cagA genotypes and EPIYA motifs were analyzed by DNA sequencing. The overall proportion of the ten cag-PAI genes that were detected ranged between 66 and 79%; additionally, approximately 48% of the strains from Thai patients contained an intact cag-PAI structure, while a significantly higher proportion (80%) of the strains from Korean patients had an intact cag-PAI. A significantly higher proportion of IS605 was detected in strains from Thai patients (55%). Analysis of cagA genotypes and EPIYA motifs revealed a higher frequency of Western-type cagA in Thai patients (87%) relative to Korean patients (8%) who were predominately associated with the East Asian-type cagA (92%). Variations in the Western-type cagA in the Thai population, such as EPIYA-BC patterns and EPIYA-like sequences (EPIYT), were mainly detected as compared with the Korean population (p < 0.05). In summary, H. pylori strains that colonize the Thai population tend to be associated with low virulence due to distinctive cag-PAI variation, which may partially explain the Asian paradox phenomenon in Thailand.
Assuntos
Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Úlcera Péptica/microbiologia , Variação Genética , Ilhas Genômicas , Genótipo , Helicobacter pylori/classificação , Helicobacter pylori/isolamento & purificação , Humanos , República da Coreia , Análise de Sequência de DNA , TailândiaRESUMO
BACKGROUND: Helicobacter pylori, a bacterium that infects the human stomach, has high genetic diversity. Because its evolution is parallel to human, H. pylori is used as a tool to trace human migration. However, there are few studies about the relationship between phylogeography of H. pylori and its host human. METHODS: We examined both H. pylori DNA and the host mitochondrial DNA and Y-chromosome DNA obtained from a total 119 patients in the Dominican Republic, where human demography consists of various ancestries. DNA extracted from cultured H. pylori were analyzed by multi locus sequence typing. Mitochondrial DNA and Y-chromosome DNA were evaluated by haplogroup analyses. RESULTS: H. pylori strains were divided into 2 populations; 68 strains with African group (hpAfrica1) and 51 strains with European group (hpEurope). In Y-chromosomal haplogroup, European origin was dominant, whereas African origin was dominant both in H. pylori and in mtDNA haplogroup. These results supported the hypothesis that mother-to-child infection is predominant in H. pylori infection. The Amerindian type of mtDNA haplogroup was observed in 11.8% of the patients; however, Amerindian type (hspAmerind) of H. pylori was not observed. Although subpopulation type of most hpAfrica1 strains in Central America and South America were hybrid (hspWAfrica/hpEurope), most Dominican Republic hpAfrica1 strains were similar to those of African continent. CONCLUSIONS: Genetic features of H. pylori, mtDNA, and Y haplogroups reflect the history of colonial migration and slave trade in the Dominican Republic. Discrepancy between H. pylori and the host human genotypes support the hypothesis that adaptability of hspAmerind H. pylori strains are weaker than hpEurope strains. H. pylori strains in the Dominican Republic seem to contain larger proportion of African ancestry compared to other American continent strains.
Assuntos
Helicobacter pylori/genética , Migração Humana , Adulto , Idoso , Cromossomos Humanos Y , DNA Mitocondrial/genética , República Dominicana , Feminino , Genótipo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/classificação , Genética Humana , Humanos , Transmissão Vertical de Doenças Infecciosas , Masculino , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Filogeografia , Adulto JovemRESUMO
BACKGROUND: Helicobacter pylori recurrence after successful eradication is an important problem. Children are particularly vulnerable to reinfection, by intrafamilial transmission which facilitates the acquisition or recombination of new genetic information by this bacterium. We investigated the evolutionary dynamics of 80 H. pylori strains isolated from two paediatric patients with recurrent infection (recrudescence and reinfection). RESULTS: We characterized the virulence genes vacA (s1, m1, s2, and m2), cagA, cagE, and babA2 and performed multilocus sequence typing (MLST) on 7 housekeeping genes (atpA, efp, ureI, ppa, mutY, trpC, and yphC) to infer the evolutionary dynamics of the H. pylori strains through phylogenetic and genealogic inference analyses, genetic diversity analysis and the exploration of recombination events during recurrent infections. The virulence genotype vacAs1m1/cagA+/cagE+/babA2 was present at a high frequency, as were the EPIYA motifs EPIYA-A, -B and -C. Furthermore, the housekeeping genes of the H. pylori strains exhibited high genetic variation, comprising 26 new alleles and 17 new Sequence Type (ST). In addition, the hpEurope (76.5%) and hspWAfrica (23.5%) populations predominated among the paediatric strains. All strains, regardless of their ancestral affiliation, harboured western EPIYA motifs. CONCLUSIONS: This study provides evidence of the evolutionary dynamics of the H. pylori strains in two paediatric patients during recrudescence and reinfection events. In particular, our study shows that the strains changed during these events, as evidenced by the presence of different STs that emerged before and after treatment; these changes may be due to the accumulation of mutations and recombination events during the diversification process and recolonization of the patients by different genotypes.
Assuntos
Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Genótipo , Helicobacter pylori/classificação , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Humanos , Lactente , Masculino , Pediatria , Filogenia , Recidiva , Fatores de Virulência/genéticaRESUMO
BACKGROUND: Antimicrobial resistance is a global public health problem, particularly in low- and middle-income countries (LMICs), where antibiotics are often obtained without a prescription. H. pylori antimicrobial resistance patterns are informative for patient care and gastric cancer prevention programs, have been shown to correlate with general antimicrobial consumption, and may guide antimicrobial stewardship programs in LMICs. We report H. pylori resistance and antimicrobial utilization patterns for western Honduras, representative of rural Central America. METHODS: In the context of the western Honduras gastric cancer epidemiology initiative, gastric biopsies from 189 patients were studied for culture and resistance patterns. Antimicrobial utilization was investigated for common H. pylori treatment regimens from regional public (7 antimicrobials) and national private (4 antimicrobials) data, analyzed in accordance with WHO anatomical therapeutic chemical defined daily doses (DDD) method and expressed as DDD/1000 inhabitants per day (DID) and per year (DIY). RESULTS: H. pylori was successfully cultured from 116 patients (56% males, mean age: 54), and nearly all strains were cagA+ and vacAs1m1+ positive (99% and 90.4%, respectively). Unexpectedly, high resistance was noted for levofloxacin (20.9%) and amoxicillin (10.7%), while metronidazole (67.9%) and clarithromycin (11.2%) were similar to data from Latin America. Significant associations with age, gender, or histology were not noted, with the exception of levofloxacin (28%, P = 0.01) in those with histology limited to non-atrophic gastritis. Total antimicrobial usage in western Honduras of amoxicillin (17.3 DID) and the quinolones had the highest relative utilizations compared with other representative nations. CONCLUSIONS: We observed significant H. pylori resistance to amoxicillin and levofloxacin in the context of high community antimicrobial utilization. This has implications in Central America for H. pylori treatment guidelines as well as antimicrobial stewardship programs.
Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Adulto , Idoso , Amoxicilina/uso terapêutico , América Central , Feminino , Infecções por Helicobacter/microbiologia , Helicobacter pylori/classificação , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Levofloxacino/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-IdadeRESUMO
Despite extensive studies on the gastric microbiota, including Helicobacter pylori and non-H. pylori, the bacterial composition in children remains unknown. In this study, we analyzed the culturable gastric bacteria in stomach biopsies from 346 children aged 1-15 years affected by gastric diseases. H. pylori and non-H. pylori were identified by specific PCR and 16S rDNA sequencing, respectively. Antibiotic susceptibilities of H. pylori and non-H. pylori were tested by the E-test and disk diffusion methods, respectively. Rapid diagnosis was also performed by H. pylori-specific PCR. Twenty-two H. pylori strains were obtained from culture, and 92 biopsies were positive by H. pylori-specific PCR. The positive rate was higher in boys (40.3%) than in girls (23.3%) (P = 0.001). Resistance rates of 22 H. pylori strains were as follows: metronidazole, 86.4%; tetracycline, 22.7%; amoxicillin, 22.7%; levofloxacin, 31.8%; clarithromycin, 36.4%. Ten isolates were multidrug-resistant. Additionally, among 366 non-H. pylori strains, 204 exhibited urease activity. Non-H. pylori resistance rates were as follows: metronidazole, 94.8%; tetracycline, 26.2%; amoxicillin, 42.6%; levofloxacin, 15.3%; clarithromycin, 46.7%. Our results showed that children with gastric disorders harbor stomach bacteria with urease activity or nitrate reductase activity. Further studies will determine the effects of non-H. pylori bacteria in gastric diseases.
Assuntos
Antibacterianos/farmacologia , Microbioma Gastrointestinal , Gastropatias/microbiologia , Estômago/microbiologia , Adolescente , Criança , Pré-Escolar , Farmacorresistência Bacteriana Múltipla , Feminino , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/classificação , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Filogenia , Estômago/patologia , Gastropatias/patologiaRESUMO
Introducción: la infección por Helicobacter pylori es un problema de salud pública, dada su relación con cáncer gástrico. El incremento de la resistencia bacteriana limita la erradicación efectiva, a pesar del empleo de diferentes esquemas de tratamiento. Métodos: revisión de la literatura en la base de datos Pubmed/Medline entre el 1 de enero de 2015 y el 31 de diciembre de 2016 sobre el manejo del Helicobacter pylori. Resultados: se incluyeron 26 artículos. La terapia secuencial sobresale como opción de tratamiento de primera línea para escenarios como Colombia. La implementación de coadyuvantes puede influir en las tasas de erradicación. Los estudios de epidemiología local y costo-efectividad son escasos. Conclusiones: el uso y conocimiento adecuado de los esquemas de manejo puede disminuir los costos para el sistema, la resistencia antimicrobiana y favorecer la erradicación de patógenos. Se requieren estudios para generar recomendaciones locales.
Introduction: Helicobacter pylori (H. pylori) infection is a public health problem due to its relationship with gastric cáncer The escalation of antibiotic resistance hampers an effective eradication, despite the availability of treatment options. Methods: A review of the literature was performed in the database PubMed between 01/01/2015 and 31/31/2016. Results: Twenty six articles were included. Sequential therapy stands out as a first line therapy for scenarios such as Colombia. The implementation of adjuvants may have a positive impact on eradication rates. Local epidemiólogo- and cost-effectiveness studies are scarce. The results were analized by erradication therapies, coadyuvant treatment, guidelines and outcomes non mentioned in the guidelines. Conclusions: The correct use and knowledge of the different treatment options could reduce the costs for the health systems, the antibiotics resistance and could favor pathogen eradication. Further studies are required for establishing local recommendations.
Assuntos
Helicobacter pylori/classificação , Guias de Prática Clínica como Assunto , Terapia Combinada/métodos , Tratamento Farmacológico/métodos , Antibacterianos/análiseRESUMO
Helicobacter pylori (Hp) is the primary cause of gastric cancer but we know little of its relative abundance and other microbes in the stomach, especially at the time of gastric cancer diagnosis. Here we characterized the taxonomic and derived functional profiles of gastric microbiota in two different sets of gastric cancer patients, and compared them with microbial profiles in other body sites. Paired non-malignant and tumor tissues were sampled from 160 gastric cancer patients with 80 from China and 80 from Mexico. The 16S rRNA gene V3-V4 region was sequenced using MiSeq platform for taxonomic profiles. PICRUSt was used to predict functional profiles. Human Microbiome Project was used for comparison. We showed that Hp is the most abundant member of gastric microbiota in both Chinese and Mexican samples (51 and 24%, respectively), followed by oral-associated bacteria. Taxonomic (phylum-level) profiles of stomach microbiota resembled oral microbiota, especially when the Helicobacter reads were removed. The functional profiles of stomach microbiota, however, were distinct from those found in other body sites and had higher inter-subject dissimilarity. Gastric microbiota composition did not differ by Hp colonization status or stomach anatomic sites, but did differ between paired non-malignant and tumor tissues in either Chinese or Mexican samples. Our study showed that Hp is the dominant member of the non-malignant gastric tissue microbiota in many gastric cancer patients. Our results provide insights on the gastric microbiota composition and function in gastric cancer patients, which may have important clinical implications.
Assuntos
Bactérias/isolamento & purificação , Microbioma Gastrointestinal , Neoplasias Gástricas/microbiologia , Estômago/microbiologia , Adulto , Idoso , Bactérias/classificação , Bactérias/genética , China , Feminino , Helicobacter pylori/classificação , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , México , Pessoa de Meia-Idade , Adulto JovemRESUMO
Abstract The severity of Helicobacter pylori-related disease is correlated with the presence and integrity of a cag pathogenicity island (cagPAI). cagPAI genotype may have a modifying effect on the pathogenic potential of the infecting strain. After analyzing the sequences of cagPAI genes, some strains with the East Asian-type cagPAI genes were selected for further analysis to examine the association between the diversity of the cagPAI genes and the virulence of H. pylori. The results showed that gastric mucosal inflammatory cell infiltration was significantly higher in patients with East Asian-type cagPAI genes H. pylori strain compared with mosaicism cagPAI genes H. pylori strain (p < 0.05). H. pylori strains with the East Asian-type cagPAI genes were closely associated with IL-8 secretion in vitro and in vivo compared with H. pylori strains with the mosaicism cagPAI genes (p < 0.01). H. pylori strains with East Asian-type cagPAI genes are able to strongly translocate CagA to host cells. These results suggest that H. pylori strains with East Asian-type cagPAI genes are more virulent than the strains of cagPAI gene/genes that are Western type.
Assuntos
Humanos , Helicobacter pylori/classificação , Helicobacter pylori/genética , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Ilhas Genômicas , Genótipo , Filogenia , Virulência , Análise por Conglomerados , Helicobacter pylori/isolamento & purificação , Fatores de Virulência/genética , Mucosa Gástrica/patologia , Histocitoquímica , MicroscopiaRESUMO
AIM: To evaluate effect of treatment failure on cagA and vacA genotypes in Helicobacter pylori (H. pylori) isolates from Colombia. METHODS: One hundred and seventy-six participants infected with H. pylori from Colombia were treated during 14 d with the triple-standard therapy. Six weeks later, eradication was evaluated by 13C-Urea breath test. Patients with treatment failure were subjected to endoscopy control; biopsies obtained were used for histopathology and culture. DNA from H. pylori isolates was amplified using primers specific for cagA and vacA genes. The phylogenetic relationships among isolates obtained before and after treatment were established by conglomerate analysis based on random amplified polymorphic DNA (RAPD) fingerprinting. RESULTS: Treatment effectiveness was at 74.6%. Of the participants with treatment failure, 25 accepted subjected to a second endoscopy. Prevalence of post-treatment infection was 64% (16/25) and 40% (10/25) by histology and culture, respectively. Upon comparing the cagA and vacA genotypes found before and after therapy, multiple cagA genotypes (cagA-positive and cagA-negative) were found before treatment; in contrast, cagA-negative genotypes decreased after treatment. vacA s1m1 genotype was highly prevalent in patients before and after therapy. The 3'cagA region was successfully amplified in 95.5% (21/22) of the isolates obtained before and in 81.8% (18/22) of the isolates obtained after treatment. In the isolates obtained from patients with treatment failure, it was found that 72.7% (16/22) presented alterations in the number of EPIYA motifs, compared to isolates found before treatment. CONCLUSION: Unsuccessful treatment limits colonization by low-virulence strains resulting in partial and selective eradication in mixed infections, and acts on the cagA-positive strains inducing genetic rearrangements in cagA variable region that produces a loss or gain of EPIYA repetitions.
Assuntos
Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/genética , Helicobacter pylori/patogenicidade , Fatores de Virulência/genética , Adulto , Motivos de Aminoácidos , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Antígenos de Bactérias/isolamento & purificação , Proteínas de Bactérias/isolamento & purificação , Biópsia , Testes Respiratórios , Claritromicina/uso terapêutico , Colômbia/epidemiologia , Quimioterapia Combinada , Endoscopia Gastrointestinal , Feminino , Genótipo , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/classificação , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Omeprazol/uso terapêutico , Filogenia , Prevalência , Inibidores da Bomba de Prótons/uso terapêutico , Técnica de Amplificação ao Acaso de DNA Polimórfico , Falha de Tratamento , Resultado do Tratamento , Fatores de Virulência/isolamento & purificaçãoRESUMO
BACKGROUND: The human gastric colonizer Helicobacter pylori is useful to track human migrations given the agreement between the bacterium phylogeographic distribution and human migrations. As Portugal was an African and Brazilian colonizer for over 400 years, we hypothesized that Portuguese isolates were likely genetically closer with those from countries colonized by Portuguese in the past. We aimed to characterize the population structure of several Portuguese-speaking countries, including Portugal, Brazil, Angola, and Cape Verde. MATERIALS AND METHODS: We included strains isolated in Portugal from Portuguese and from former Portuguese colonies. These strains were typed by multilocus sequence typing (MLST) for seven housekeeping genes. We also retrieved from Multi Locus Sequence Typing Web site additional housekeeping gene sequences, namely from Angola and Brazil. RESULTS: We provided evidence that strains from Portuguese belong to hpEurope and that the introgression of hpEurope in non-European countries that speak Portuguese is low, except for Brazil and Cape Verde, where hpEurope accounted for one quarter and one half of the population, respectively. We found genetic similarity for all strains from Portuguese-speaking countries that belong to hpEurope population. Moreover, these strains showed a predominance of ancestral Europe 2 (AE2) over ancestral Europe 1 (AE1), followed by ancestral Africa 1. CONCLUSIONS: H. pylori is a useful marker even for relative recent human migration events and may become rapidly differentiated from founder populations. H. pylori from Portuguese-speaking countries assigned to hpEurope appears to be a hybrid population resulting from the admixture of AE1, AE2 and ancestral hpAfrica1.
Assuntos
Variação Genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/classificação , Helicobacter pylori/genética , Angola , Brasil , Cabo Verde , Genética Populacional , Genótipo , Helicobacter pylori/isolamento & purificação , Migração Humana , Humanos , Tipagem de Sequências Multilocus , PortugalRESUMO
The severity of Helicobacter pylori-related disease is correlated with the presence and integrity of a cag pathogenicity island (cagPAI). cagPAI genotype may have a modifying effect on the pathogenic potential of the infecting strain. After analyzing the sequences of cagPAI genes, some strains with the East Asian-type cagPAI genes were selected for further analysis to examine the association between the diversity of the cagPAI genes and the virulence of H. pylori. The results showed that gastric mucosal inflammatory cell infiltration was significantly higher in patients with East Asian-type cagPAI genes H. pylori strain compared with mosaicism cagPAI genes H. pylori strain (p<0.05). H. pylori strains with the East Asian-type cagPAI genes were closely associated with IL-8 secretion in vitro and in vivo compared with H. pylori strains with the mosaicism cagPAI genes (p<0.01). H. pylori strains with East Asian-type cagPAI genes are able to strongly translocate CagA to host cells. These results suggest that H. pylori strains with East Asian-type cagPAI genes are more virulent than the strains of cagPAI gene/genes that are Western type.
Assuntos
Ilhas Genômicas , Genótipo , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/classificação , Helicobacter pylori/genética , Fatores de Virulência/genética , Análise por Conglomerados , Mucosa Gástrica/patologia , Helicobacter pylori/isolamento & purificação , Histocitoquímica , Humanos , Microscopia , Filogenia , VirulênciaRESUMO
BACKGROUND: Helicobacter pylori (H. pylori) is one of the most common bacterial infections in humans and this infection can lead to gastric ulcers and gastric cancer. H. pylori is one of the most genetically variable human pathogens and the ability of the bacterium to bind to the host epithelium as well as the presence of different virulence factors and genetic variants within these genes have been associated with disease severity. Nicaragua has particularly high gastric cancer incidence and we therefore studied Nicaraguan clinical H. pylori isolates for factors that could contribute to cancer risk. METHODS: The complete genomes of fifty-two Nicaraguan H. pylori isolates were sequenced and assembled de novo, and phylogenetic and virulence factor analyses were performed. RESULTS: The Nicaraguan isolates showed phylogenetic relationship with West African isolates in whole-genome sequence comparisons and with Western and urban South- and Central American isolates using MLSA (Multi-locus sequence analysis). A majority, 77 % of the isolates carried the cancer-associated virulence gene cagA and also the s1/i1/m1 vacuolating cytotoxin, vacA allele combination, which is linked to increased severity of disease. Specifically, we also found that Nicaraguan isolates have a blood group-binding adhesin (BabA) variant highly similar to previously reported BabA sequences from Latin America, including from isolates belonging to other phylogenetic groups. These BabA sequences were found to be under positive selection at several amino acid positions that differed from the global collection of isolates. CONCLUSION: The discovery of a Latin American BabA variant, independent of overall phylogenetic background, suggests hitherto unknown host or environmental factors within the Latin American population giving H. pylori isolates carrying this adhesin variant a selective advantage, which could affect pathogenesis and risk for sequelae through specific adherence properties.
Assuntos
Adesinas Bacterianas/genética , Helicobacter pylori/classificação , Helicobacter pylori/genética , Adesinas Bacterianas/química , Adolescente , Adulto , Idoso , Sequência de Aminoácidos , Antígenos de Bactérias/genética , Feminino , Variação Genética , Genoma Bacteriano , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Tipagem de Sequências Multilocus , Nicarágua , Filogenia , Fatores de Virulência/química , Fatores de Virulência/genética , Adulto JovemRESUMO
The objectives of the present study were to determine Helicobacter pylori via culture, polymerase chain reaction and histopathological diagnosis in 101 children ranging in age from 4 to 18 years, to identify the association among restriction fragment length polymorphism types and clinical disease and to investigate the relationships among different isolates of H. pylori in different age groups. We observed a high prevalence of H. pylori infections in children between the ages of 13 and 18 (75.8%), while children aged 4 to 6 years had the lowest prevalence of infection (40%). H. pylori was detected in 30.7% (31 of 101), 66.3% (67 of 101) and 63.2% (60 of 95) of children as determined by culture methods, PCR and histological examination, respectively. H. pylori isolates with RFLP types I and III were the most common among children with antral nodularity, whereas RFLP types II and IV were the least detected types. Interestingly, all isolates from peptic ulcer patients were type III. Although our results show a high prevalence of H. pylori infections in the pediatric population in eastern Turkey, no association was identified between H. pylori infection with antral nodularity and recurring abdominal pain. In addition, we found low genetic variation among H. pylori isolates from children and no association between RFLP types and antral nodularity (p > 0.05). Additionally, we found that H. pylori isolates with specific RFLP types were predominant in different age groups.
Assuntos
Genótipo , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/classificação , Helicobacter pylori/isolamento & purificação , Tipagem Molecular , Polimorfismo de Fragmento de Restrição , Adolescente , Fatores Etários , Técnicas Bacteriológicas , Biópsia , Criança , Pré-Escolar , Feminino , Helicobacter pylori/genética , Humanos , Masculino , Epidemiologia Molecular , Reação em Cadeia da Polimerase , Prevalência , Turquia/epidemiologiaRESUMO
The objectives of the present study were to determine Helicobacter pylori via culture, polymerase chain reaction and histopathological diagnosis in 101 children ranging in age from 4 to 18 years, to identify the association among restriction fragment length polymorphism types and clinical disease and to investigate the relationships among different isolates of H. pylori in different age groups. We observed a high prevalence of H. pylori infections in children between the ages of 13 and 18 (75.8%), while children aged 4 to 6 years had the lowest prevalence of infection (40%). H. pylori was detected in 30.7% (31 of 101), 66.3% (67 of 101) and 63.2% (60 of 95) of children as determined by culture methods, PCR and histological examination, respectively. H. pylori isolates with RFLP types I and III were the most common among children with antral nodularity, whereas RFLP types II and IV were the least detected types. Interestingly, all isolates from peptic ulcer patients were type III. Although our results show a high prevalence of H. pylori infections in the pediatric population in eastern Turkey, no association was identified between H. pylori infection with antral nodularity and recurring abdominal pain. In addition, we found low genetic variation among H. pylori isolates from children and no association between RFLP types and antral nodularity (p > 0.05). Additionally, we found that H. pylori isolates with specific RFLP types were predominant in different age groups.
Assuntos
Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Genótipo , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/classificação , Helicobacter pylori/isolamento & purificação , Tipagem Molecular , Polimorfismo de Fragmento de Restrição , Fatores Etários , Técnicas Bacteriológicas , Biópsia , Helicobacter pylori/genética , Epidemiologia Molecular , Reação em Cadeia da Polimerase , Prevalência , Turquia/epidemiologiaRESUMO
The objectives of the present study were to determine Helicobacter pylori via culture, polymerase chain reaction and histopathological diagnosis in 101 children ranging in age from 4 to 18 years, to identify the association among restriction fragment length polymorphism types and clinical disease and to investigate the relationships among different isolates of H. pylori in different age groups. We observed a high prevalence of H. pylori infections in children between the ages of 13 and 18 (75.8%), while children aged 4 to 6 years had the lowest prevalence of infection (40%). H. pylori was detected in 30.7% (31 of 101), 66.3% (67 of 101) and 63.2% (60 of 95) of children as determined by culture methods, PCR and histological examination, respectively. H. pylori isolates with RFLP types I and III were the most common among children with antral nodularity, whereas RFLP types II and IV were the least detected types. Interestingly, all isolates from peptic ulcer patients were type III. Although our results show a high prevalence of H. pylori infections in the pediatric population in eastern Turkey, no association was identified between H. pylori infection with antral nodularity and recurring abdominal pain. In addition, we found low genetic variation among H. pylori isolates from children and no association between RFLP types and antral nodularity (p > 0.05). Additionally, we found that H. pylori isolates with specific RFLP types were predominant in different age groups.(AU)
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Genótipo , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/classificação , /isolamento & purificação , Tipagem Molecular , Polimorfismo de Fragmento de Restrição , Fatores Etários , Técnicas Bacteriológicas , Biópsia , Helicobacter pylori/genética , Epidemiologia Molecular , Reação em Cadeia da Polimerase , Prevalência , Turquia/epidemiologiaRESUMO
Genotypic differences in Helicobacter pylori play an important role in infection. We characterized the diversity of the cagA, cagE, babA2, and vacA genes in H. pylori strains isolated from pediatric patients and the relationship between these genes and clinical disease. Additionally, we employed the Neighbor-net algorithm to predict the behavior of the genotypes of the strains isolated from patients. Of 93 patients analyzed, 32 were positive for infection. A total of 160 H. pylori strains (five isolates per positive patient) were analyzed. A total of 91% and 83% of strains possessed the cagA and cagE genes, respectively. For the vacA gene, 84% of strains possessed the s1 allele, 15% the s2 allele, 81% the m1 allele and 13.8% the m2 allele. The babA2 gene was present in 79% of strains. Infection with H. pylori strains with the vacA (s1m1) genotype was associated with risk of esophagitis and gastritis (p=0.0001). The combination of cagA and vacA (s1m1) was significantly associated with abdominal pain (p=0.002); however, EPIYA type was not significantly associated with abdominal pain. A total of 16 different genotypes were identified; the most common genotype was vacAs1m1cagA+cagE+babA2+ (47.5%). A total of 84% of pediatric patients were infected by at least two and up to five different genotypes. The network recovered two genotype groups (A: strains with vacAs1 and B: strains with vacAs2). The presence of multiple paths in the network suggests that reticulate events, such as recombination or reinfection, have contributed to the observed genotypic diversity.