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Li C, He L, Wang A, Chen S, Fu P, Wang C. Antibiotic resistance and virulence genes in Helicobacter pylori strains isolated from children in Shanghai, China (2019-2022). Int J Med Microbiol 2024; 315:151622. [PMID: 38776570 DOI: 10.1016/j.ijmm.2024.151622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 05/07/2024] [Accepted: 05/20/2024] [Indexed: 05/25/2024] Open
Abstract
BACKGROUND The increasing prevalence of antibiotic-resistant Helicobacter pylori strains poses a significant threat to children's health. This study investigated antibiotic resistance rates in Helicobacter pylori strains isolated from children in Shanghai and analyzed the presence of virulence genes in these strains. METHODS We obtained 201 Helicobacter pylori strains from pediatric patients with upper gastrointestinal symptoms who underwent gastrointestinal endoscopy between 2019 and 2022. Subsequently, we performed antibiotic susceptibility tests and virulence gene PCR assays on these strains. RESULTS Helicobacter pylori resistance rates of 45.8%, 15.4%, 1.0%, and 2.5% were detected for metronidazole, clarithromycin, amoxicillin, and levofloxacin, respectively. Among all isolates, 64.7% exhibited resistance to at least one antibiotic. Resistance to metronidazole and clarithromycin increased from 2019 to 2022. The predominant vacA gene subtype was vacA s1a/m2. The prevalence of vacA m2 and dupA exhibited an upward trend, while oipA presented a decreasing trend from 2019 to 2022. The prevalence of dupA was significantly higher in gastritis than peptic ulcer disease, and in non-treatment compared to treatment groups. CONCLUSIONS Helicobacter pylori antibiotic resistance remains high in children and has risen in recent years. Therefore, the increasing use of metronidazole and clarithromycin requires increased monitoring in children. No association was observed between antibiotic resistance and virulence gene phenotypes.
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Affiliation(s)
- Chunling Li
- Lab of Microbiology, Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Leiyan He
- Lab of Microbiology, Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Aimin Wang
- Lab of Microbiology, Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Saige Chen
- Lab of Microbiology, Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Pan Fu
- Lab of Microbiology, Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China; Nosocomial Infection Control Department, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Chuanqing Wang
- Lab of Microbiology, Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China; Nosocomial Infection Control Department, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
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Keikha M, Karbalaei M. Correlation between the geographical origin of Helicobacter pylori homB-positive strains and their clinical outcomes: a systematic review and meta-analysis. BMC Gastroenterol 2021; 21:181. [PMID: 33879080 PMCID: PMC8056685 DOI: 10.1186/s12876-021-01764-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 04/09/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND In general, all virulence factors of Helicobacter pylori (H. pylori) are involved in its infections. However, recent studies have shown that the homB gene is one of the virulence genes that affects the severity of the clinical results of this bacterium. METHODS The main purpose of this study was to investigate the relationship between the presence of homB gene in H. pylori and the progression of its infection to peptic ulcer and gastric cancer. In the present study, we conducted a systematic search to collect all articles related to the effect of homB-positive strains on clinical outcomes. Finally, 12 eligible studies according to our criteria were included in this meta-analysis and the effect of homB gene on gastric ulcer and gastric cancer diseases was evaluated by summary odds ratio (OR). RESULTS Current results showed that the homB-positive strains significantly increase the risk of peptic ulcer (OR 1.36; 1.07-1.72 with 95% CIs), especially in western countries (OR 1.61; 1.20-2.14 with 95% CIs). Moreover, we observed a positive association between the homB gene and risk of gastric cancer (OR 2.16; 1.37-3.40 with 95% CIs). In addition, based on subgroup analysis, it was found that the presence of this gene in H. pylori strains increases the risk of gastric cancer in the Asian population (OR 3.71; 1.85-7.45 with 95% CIs). CONCLUSIONS Overall, in the present study we found that homB gene is responsible for the progressing of primary infection to severe complications, in particular peptic ulcer in western countries and gastric cancer in Asian countries.
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Affiliation(s)
- Masoud Keikha
- Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Karbalaei
- Department of Microbiology and Virology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran.
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Crowley E, Hussey S. Helicobacter pylori in Childhood. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2021:275-292.e12. [DOI: 10.1016/b978-0-323-67293-1.00027-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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In Vivo Genome and Methylome Adaptation of cag-Negative Helicobacter pylori during Experimental Human Infection. mBio 2020; 11:mBio.01803-20. [PMID: 32843556 PMCID: PMC7448279 DOI: 10.1128/mbio.01803-20] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Exceptional genetic diversity and variability are hallmarks of Helicobacter pylori, but the biological role of this plasticity remains incompletely understood. Here, we had the rare opportunity to investigate the molecular evolution during the first weeks of H. pylori infection by comparing the genomes and epigenomes of H. pylori strain BCS 100 used to challenge human volunteers in a vaccine trial with those of bacteria reisolated from the volunteers 10 weeks after the challenge. The data provide molecular insights into the process of establishment of this highly versatile pathogen in 10 different human individual hosts, showing, for example, selection for changes in host-interaction molecules as well as changes in epigenetic methylation patterns. The data provide important clues to the early adaptation of H. pylori to new host niches after transmission, which we believe is vital to understand its success as a chronic pathogen and develop more efficient treatments and vaccines. Multiple studies have demonstrated rapid bacterial genome evolution during chronic infection with Helicobacter pylori. In contrast, little was known about genetic changes during the first stages of infection, when selective pressure is likely to be highest. Using single-molecule, real-time (SMRT) and Illumina sequencing technologies, we analyzed genome and methylome evolution during the first 10 weeks of infection by comparing the cag pathogenicity island (cagPAI)-negative H. pylori challenge strain BCS 100 with pairs of H. pylori reisolates from gastric antrum and corpus biopsy specimens of 10 human volunteers who had been infected with this strain as part of a vaccine trial. Most genetic changes detected in the reisolates affected genes with a surface-related role or a predicted function in peptide uptake. Apart from phenotypic changes of the bacterial envelope, a duplication of the catalase gene was observed in one reisolate, which resulted in higher catalase activity and improved survival under oxidative stress conditions. The methylomes also varied in some of the reisolates, mostly by activity switching of phase-variable methyltransferase (MTase) genes. The observed in vivo mutation spectrum was remarkable for a very high proportion of nonsynonymous mutations. Although the data showed substantial within-strain genome diversity in the challenge strain, most antrum and corpus reisolates from the same volunteers were highly similar to each other, indicating that the challenge infection represents a major selective bottleneck shaping the transmitted population. Our findings suggest rapid in vivo selection of H. pylori during early-phase infection providing adaptation to different individuals by common mechanisms of genetic and epigenetic alterations.
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Prevalence of the Helicobacter pylori babA2 Gene in Children Mainly Depends on the PCR Primer Set Used. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2020; 2020:4080248. [PMID: 32855749 PMCID: PMC7443014 DOI: 10.1155/2020/4080248] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 07/20/2020] [Accepted: 07/28/2020] [Indexed: 02/07/2023]
Abstract
Various polymerase chain reaction- (PCR-) based methods with varying positivity rates were designed to detect the Helicobacter pylori babA2 gene. To compare different primer sets, babA2 prevalence was determined in 279 H. pylori-positive pediatric samples using the 832 bp, 139 bp, and 271 bp PCR primer sets, resulting in 34.0%, 51.3%, and 79.6% prevalence of the babA2 gene, respectively. The babA2 status determined using the 832 bp and 139 bp PCR primer sets significantly correlated with bacterial density and activity of inflammation, whereas no such correlations were found using the 271 bp PCR primer set. The 139 and 832 bp PCR primer sets concordantly detected the babA2 gene in 93 cases; however, in comparison to the 832 bp PCR primer set, the 139 bp PCR primer set detected additional 50 babA2 cases, whereas only two 832 bp positive cases were missed. The 271 bp PCR primer set missed 32 babA2 cases that were 832 bp and/or 139 bp PCR positive, but tested solely positive in 109 cases. Interestingly, cloning of a subset of 271 bp PCR positive samples revealed amplification of the babA/B gene chimera. Hence, in our opinion, the 271 bp PCR protocol is not a reliable diagnostic tool for detecting the babA2 gene in children. Our results reaffirm previous observations that the use of certain babA2 PCR primer sets can significantly impact estimation of the prevalence and clinical relevance of the H. pylori babA2 gene in children, suggesting babA2 detection methods should be carefully selected.
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Šterbenc A, Jarc E, Poljak M, Homan M. Helicobacter pylori virulence genes. World J Gastroenterol 2019; 25:4870-4884. [PMID: 31543679 PMCID: PMC6737321 DOI: 10.3748/wjg.v25.i33.4870] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 07/29/2019] [Accepted: 08/07/2019] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is one of the most important human pathogens, infecting approximately half of the global population. Despite its high prevalence, only a subset of H. pylori infected individuals develop serious gastroduodenal pathology. The pathogenesis of H. pylori infection and disease outcome is thus thought to be mediated by an intricate interplay between host, environmental and bacterial virulence factors. H. pylori has adapted to the harsh milieu of the human stomach through possession of various virulence genes that enable survival of the bacteria in the acidic environment, movement towards the gastric epithelium, and attachment to gastric epithelial cells. These virulence factors enable successful colonization of the gastric mucosa and sustain persistent H. pylori infection, causing chronic inflammation and tissue damage, which may eventually lead to the development of peptic ulcers and gastric cancer. Numerous studies have focused on the prevalence and role of putative H. pylori virulence genes in disease pathogenesis. While several virulence factors with various functions have been identified, disease associations appear to be less evident, especially among different study populations. This review presents key findings on the most important H. pylori virulence genes, including several bacterial adhesins and toxins, in children and adults, and focuses on their prevalence, clinical significance and potential relationships.
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Affiliation(s)
- Anja Šterbenc
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Erika Jarc
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Mario Poljak
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Matjaž Homan
- Department of Gastroenterology, Hepatology and Nutrition, University Children’s Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
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Quintana-Hayashi MP, Rocha R, Padra M, Thorell A, Jin C, Karlsson NG, Roxo-Rosa M, Oleastro M, Lindén SK. BabA-mediated adherence of pediatric ulcerogenic H. pylori strains to gastric mucins at neutral and acidic pH. Virulence 2019; 9:1699-1717. [PMID: 30298790 PMCID: PMC7000205 DOI: 10.1080/21505594.2018.1532243] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Helicobacter pylori infection can result in non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), adenocarcinoma, and gastric lymphoma. H. pylori reside within the gastric mucus layer, mainly composed of mucins carrying an array of glycan structures that can serve as bacterial adhesion epitopes. The aim of the present study was to characterize the binding ability, adhesion modes, and growth of H. pylori strains from pediatric patients with NUD and PUD to gastric mucins. Our results showed an increased adhesion capacity of pediatric PUD H. pylori strains to human and rhesus monkey gastric mucins compared to the NUD strains both at neutral and acidic pH, regardless if the mucins were positive for Lewis b (Leb), Sialyl-Lewis x (SLex) or LacdiNAc. In addition to babA positive strains being more common among PUD associated strains, H. pylori babA positive strains bound more avidly to gastric mucins than NUD babA positive strains at acidic pH. Binding to Leb was higher among babA positive PUD H. pylori strains compared to NUD strains at neutral, but not acidic, pH. PUD derived babA-knockout mutants had attenuated binding to mucins and Leb at acidic and neutral pH, and to SLex and DNA at acidic pH. The results highlight the role of BabA-mediated adherence of pediatric ulcerogenic H. pylori strains, and points to a role for BabA in adhesion to charged structures at acidic pH, separate from its specific blood group binding activity.
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Affiliation(s)
- Macarena P Quintana-Hayashi
- a Department of Biomedical Chemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy , University of Gothenburg , Gothenburg , Sweden
| | - Raquel Rocha
- b Department of Infectious Diseases , National Institute of Health Dr. Ricardo Jorge , Lisbon , Portugal
| | - Médea Padra
- a Department of Biomedical Chemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy , University of Gothenburg , Gothenburg , Sweden
| | - Anders Thorell
- c Department for Clinical Science and Department of Surgery, Ersta Hospital , Karolinska Institutet , Stockholm , Sweden
| | - Chunsheng Jin
- a Department of Biomedical Chemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy , University of Gothenburg , Gothenburg , Sweden
| | - Niclas G Karlsson
- a Department of Biomedical Chemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy , University of Gothenburg , Gothenburg , Sweden
| | - Mónica Roxo-Rosa
- b Department of Infectious Diseases , National Institute of Health Dr. Ricardo Jorge , Lisbon , Portugal
| | - Mónica Oleastro
- d Centro de Estudo de Doenças Crónicas, Nova Medical School/Faculdade de Ciências Médicas , Universidade Nova de Lisboa , Lisbon , Portugal
| | - Sara K Lindén
- a Department of Biomedical Chemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy , University of Gothenburg , Gothenburg , Sweden
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Braga LLBC, Batista MHR, de Azevedo OGR, da Silva Costa KC, Gomes AD, Rocha GA, Queiroz DMM. oipA "on" status of Helicobacter pylori is associated with gastric cancer in North-Eastern Brazil. BMC Cancer 2019; 19:48. [PMID: 30630444 PMCID: PMC6327388 DOI: 10.1186/s12885-018-5249-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 12/26/2018] [Indexed: 12/15/2022] Open
Abstract
Background Although, outer membrane protein OipA of Helicobacter pylori has been associated with gastric mucosal damage and gastroduodenal diseases, studies evaluating gastric cancer patients are scarce. We investigated whether the functional oipA “on” status was associated with gastric cancer in the North-eastern Brazil, region with high prevalence of gastric cancer. Methods We included samples from 95 H. pylori positive subjects (23 patients with gastritis, 24 with gastric cancer, 32 first-degree relatives of gastric cancer patients and 16 children). oipA was assayed by polymerase chain reaction (PCR) and DNA sequencing. cagA and vacA status were evaluated by PCR. Results Overall 81.1% of the H. pylori strains had functional oipA. In adults, the oipA “on” status (OR = 9.20; 95%CI = 1.45–58.48, P = 0.02) and increasing age (OR = 1.08; 95%CI = 1.03–1.14; P = 0.003) were independently associated with gastric cancer in a logistic model. The oipA “on” status (OR = 14.75; 95%CI: 2.53–86.13, P = 0.003) was also associated with first-degree relatives of gastric cancer patients when compared with gastritis. The frequency of oipA “on” status did not differ between children and adults (P = 0.87). The oipA “on” status was significantly correlated with the presence of cagA and vacA s1 m1. Conclusion oipA “on” status was independently associated with gastric cancer and first-degree relatives of gastric cancer patients in North-eastern Brazil.
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Affiliation(s)
- Lúcia Libanez Bessa Campelo Braga
- Clinical Research Unit, University Hospital Walter Cantídio/Department of Internal Medicine, Universidade Federal do Ceará, Fortaleza, Brazil
| | | | | | | | - Adriana Dias Gomes
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190 - Sala 216, Belo Horizonte, CEP: 30130-100, Brazil
| | - Gifone Aguiar Rocha
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190 - Sala 216, Belo Horizonte, CEP: 30130-100, Brazil
| | - Dulciene Maria Magalhães Queiroz
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190 - Sala 216, Belo Horizonte, CEP: 30130-100, Brazil.
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Whitmire JM, Merrell DS. Helicobacter pylori Genetic Polymorphisms in Gastric Disease Development. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1149:173-194. [DOI: 10.1007/5584_2019_365] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Šterbenc A, Poljak M, Zidar N, Luzar B, Homan M. Prevalence of the Helicobacter pylori homA and homB genes and their correlation with histological parameters in children. Microb Pathog 2018; 125:26-32. [PMID: 30195645 DOI: 10.1016/j.micpath.2018.09.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 09/03/2018] [Accepted: 09/05/2018] [Indexed: 12/16/2022]
Abstract
The significance of Helicobacter pylori (H. pylori) virulence genes such as cagA and vacA has been extensively studied in children; however, data regarding the significance of homA and homB genes are scarce. The aim of our study was to evaluate the prevalence and clinical relevance of these genes in Slovenian children. All children diagnosed with H. pylori infection between 1993 and 2013 were included in the study (n = 343). DNA was extracted from biopsy specimens previously used for the rapid urease test. Five histological parameters were evaluated and the presence of the vacA, cagA, iceA, babA2, and homA and homB genes was determined by PCR amplification. The homA and homB genes were detected in 174/285 (61.1%) and 116/285 (40.7%) strains, respectively. The presence of the homA gene was significantly associated with the absence of the homB gene (P < 0.001); however, no associations were found between the presence of either the homA or homB genes and any of the other investigated virulence genes. Similarly, there were no correlations between the presence of the homA and homB genes and any of the histological parameters. In contrast, genotype profiles vacA s1m1/cagA+/babA2+/homB+, vacA s1m2/cagA+/babA2+/homA+, vacA s1m1/cagA+/babA2+/homA+, vacA s1m1/cagA+/babA2-/homA+, vacA s1m2/cagA-/babA2-/homA+, and vacA s2m2/cagA-/babA2-/homB+ were associated with a higher degree of gastric mucosal damage. Thus, although the homA and homB genes did not represent important individual virulence markers in this population, they may act synergistically with other H. pylori virulence genes, causing severe gastritis in children.
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Affiliation(s)
- Anja Šterbenc
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Mario Poljak
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Nina Zidar
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Boštjan Luzar
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Matjaž Homan
- Department of Gastroenterology, Hepatology, and Nutrition, University Children's Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
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Pormohammad A, Ghotaslou R, Leylabadlo HE, Nasiri MJ, Dabiri H, Hashemi A. Risk of gastric cancer in association with Helicobacter pylori different virulence factors: A systematic review and meta-analysis. Microb Pathog 2018; 118:214-219. [PMID: 29510208 DOI: 10.1016/j.micpath.2018.03.004] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2017] [Revised: 02/28/2018] [Accepted: 03/02/2018] [Indexed: 02/07/2023]
Abstract
INTRODUCTION It has been proposed that specific analysis of Helicobacter pylori virulence factors can be suitable for predicting of post H. pylori infection disorders like gastric cancer (GC). The present study was designed to evaluate the association between different virulence factors of H. pylori and GC. METHODS Studies investigated the association between virulence factors of H. pylori and GC were collected from the several databases. All analysis was performed by Comprehensive Meta-Analysis V2.2 software (Biostat, Englewood, NJ, USA). RESULTS Based on a comprehensive literature search, 25 eligible studies were included for meta-analyses. Infection with cagA- and vacA s1m1-positive H. pylori strains were significantly associated with increased risk of GC (OR of [2.82 (95% CI 1.96-4.06), P < 0.001]) and ([1.75 (95% CI 1.04-2.96), P 0.034)], respectively. CONCLUSIONS Infection by H. pylori strains with positive vacA s1m1 and the cagA genes can significantly increase the risk of GC. The association between the vacA s1m1 and the cagA and GC, suggests that screening of these genes may be helpful for identifying populations at higher risk for GC.
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Affiliation(s)
- Ali Pormohammad
- Student Research Committee, Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Reza Ghotaslou
- Infectious and Tropical Diseases Research Center and Department of Medical Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
| | | | - Mohammad Javad Nasiri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Dabiri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Hashemi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Subsomwong P, Miftahussurur M, Uchida T, Vilaichone RK, Ratanachu-Ek T, Mahachai V, Yamaoka Y. Prevalence, risk factors, and virulence genes of Helicobacter pylori among dyspeptic patients in two different gastric cancer risk regions of Thailand. PLoS One 2017; 12:e0187113. [PMID: 29084246 PMCID: PMC5662176 DOI: 10.1371/journal.pone.0187113] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Accepted: 10/13/2017] [Indexed: 12/16/2022] Open
Abstract
Gastric cancer risk is varied among different regions of Thailand. We examined the characteristics of Helicobacter pylori infection in two regions of Thailand. The H. pylori status of 273 dyspeptic patients (136 from the South and 137 from the North; a low and high incidence of gastric cancer region, respectively) was evaluated, and virulence genotypes (cagA, vacA, hrgA and jhp0562-positive/β-(1,3)galT) were determined. The overall H. pylori infection rate was 34.1% (93/273). The prevalence was higher in the North than in the South (50.4% vs. 17.6%, P <0.001) and was significantly higher among individuals with the following characteristics: low income, birthplace in the Northeast or North regions, agricultural employment, or consumption of alcohol or unboiling water. Among these socio-demographic determinants, region was an independent risk factor for H. pylori infection (odds ratio = 6.37). Patients including both H. pylori infected and uninfected cases who lived in the North had significantly more severe histological scores than those in the South. In contrast, among H. pylori-positive cases, patients in the South had significantly more severe histological scores than those in the North. Of the 74 strains cultured, 56.8% carried Western-type cagA, with a higher proportion in the South than in the North (76.2% vs. 49.1%, P = 0.05). In disagreement with the current consensus, patients infected with the Western-type cagA strains had more severe inflammation scores in the antrum than those infected with the East Asian-type cagA strains (P = 0.027). Moreover, Western-type cagA strains induced more severe histological scores in patients from the South than those of either genotype from the North. Other virulence genes had no influence on histological scores. The incidence of gastric cancer in Thailand was different among regions and corresponded to differences in the prevalence of H. pylori infection. More careful follow-up for patients in the South will be required, even if they are infected with H. pylori carrying Western-type cagA.
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Affiliation(s)
- Phawinee Subsomwong
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
| | - Muhammad Miftahussurur
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan.,Gastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine-Dr. Soetomo Teaching Hospital-Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.,Department of Gastroenterology and Hepatology, Baylor College of Medicine and Michael DeBakey Veterans Affairs Medical Center, Houston, Texas, United States of America
| | - Tomohisa Uchida
- Department of Molecular Pathology, Faculty of Medicine, Oita University, Hasama-machi, Yufu-City, Oita, Japan
| | - Ratha-Korn Vilaichone
- Gastroenterology Unit, Department of Medicine, Thammasat University Hospital, Pathum Thani, Thailand
| | | | | | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan.,Department of Gastroenterology and Hepatology, Baylor College of Medicine and Michael DeBakey Veterans Affairs Medical Center, Houston, Texas, United States of America
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Sharma RP, Miftahussurur M, Shrestha PK, Subsomwong P, Uchida T, Yamaoka Y. Nepalese Helicobacter pylori Genotypes Reflects a Geographical Diversity than a True Virulence Factor. Asian Pac J Cancer Prev 2017; 18:2637-2641. [PMID: 29072057 PMCID: PMC5747382 DOI: 10.22034/apjcp.2017.18.10.2637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Background: The data about the association between Helicobacter pylori putative virulence factors; iceA and jhp0562/β-(1,3)galT with clinical outcomes are still controversial. We identified and analyzed two putative H. pylori virulence factors in Nepalese strains. Methods: The iceA and jhp0562/β-(1,3)galT allelic types were determined by polymerase chain reaction amplification. Histological analysis were classified according to the updated Sydney system and the Operative Link on Gastritis Assessment (OLGA) system. Results: Among 49 strains, iceA1 negative/iceA2 positive (iceA2-positive) was predominant type (57.1%, 28/49) and 20 (40.8%) were iceA1 positive/iceA2 negative. The remaining one (2.0%) was positive for both iceA1 and iceA2 (iceA1/iceA2-mixed). Patients infected with iceA1-positive strains tended to be higher OLGA score than iceA2-positive strains [1.45 [1] vs. 0.07 [0.5], P = 0.09, respectively). The jhp0562 negative/β-(1,3)galT positive was predominant type (25/51, 49.0%), followed by double positive for jhp0562/β-(1,3)galT (15/51, 29.4%) and jhp0562 positive/β-(1,3)galT negative (11/51, 21.6%). Activity in the corpus was significantly higher in jhp0562 negative/β-(1,3)galT positive than double positive of jhp0562/β-(1,3)galT positive [mean (median); 1.24 (1) vs. 0.73 (1), P = 0.03]. There was association between iceA and subtype of vacA signal region (e.g., s1a, s1b or s1c) and combination subtypes of signal and middle regions (e.g., s1a-m1c) (P = 0.02, r = 0.29; and P = 0.002, r = 0.42, respectively). In addition, jhp0562/β-(1,3)galT genotypes associated with cagA pre-EPIYA type (e.g., 6 bp-, 18 bp-, or no deletion-type) (P = 0.047, r = 0.15). Conclusion: The inconsistency results of the association between iceA, jhp0562/β-(1,3)galT and histological scores suggesting that these genes may associate with genetic heterogeneity rather than as a true virulence factor.
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Divergence between the Highly Virulent Zoonotic Pathogen Helicobacter heilmannii and Its Closest Relative, the Low-Virulence "Helicobacter ailurogastricus" sp. nov. Infect Immun 2015; 84:293-306. [PMID: 26527212 DOI: 10.1128/iai.01300-15] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2015] [Accepted: 10/26/2015] [Indexed: 12/21/2022] Open
Abstract
Helicobacter heilmannii naturally colonizes the stomachs of dogs and cats and has been associated with gastric disorders in humans. Nine feline Helicobacter strains, classified as H. heilmannii based on ureAB and 16S rRNA gene sequences, were divided into a highly virulent and a low-virulence group. The genomes of these strains were sequenced to investigate their phylogenetic relationships, to define their gene content and diversity, and to determine if the differences in pathogenicity were associated with the presence or absence of potential virulence genes. The capacities of these helicobacters to bind to the gastric mucosa were investigated as well. Our analyses revealed that the low-virulence strains do not belong to the species H. heilmannii but to a novel, closely related species for which we propose the name Helicobacter ailurogastricus. Several homologs of H. pylori virulence factors, such as IceA1, HrgA, and jhp0562-like glycosyltransferase, are present in H. heilmannii but absent in H. ailurogastricus. Both species contain a VacA-like autotransporter, for which the passenger domain is remarkably larger in H. ailurogastricus than in H. heilmannii. In addition, H. ailurogastricus shows clear differences in binding to the gastric mucosa compared to H. heilmannii. These findings highlight the low-virulence character of this novel Helicobacter species.
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da Costa DM, Pereira EDS, Rabenhorst SHB. What exists beyond cagA and vacA? Helicobacter pylori genes in gastric diseases. World J Gastroenterol 2015; 21:10563-72. [PMID: 26457016 PMCID: PMC4588078 DOI: 10.3748/wjg.v21.i37.10563] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Revised: 06/13/2015] [Accepted: 08/25/2015] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is present in more than half the world's population and has been associated with several gastric disorders, such as gastritis, peptic ulceration, and gastric adenocarcinoma. The clinical outcome of this infection depends on host and bacterial factors where H. pylori virulence genes seem to play a relevant role. Studies of cagA and vacA genes established that they were determining factors in gastric pathogenesis. However, there are gastric cancer cases that are cagA-negative. Several other virulence genes have been searched for, but these genes remain less well known that cagA and vacA. Thus, this review aimed to establish which genes have been suggested as potentially relevant virulence factors for H. pylori-associated gastrointestinal diseases. We focused on the cag-pathogenicity island, genes with adherence and motility functions, and iceA based on the relevance shown in several studies in the literature.
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Miftahussurur M, Syam AF, Makmun D, Nusi IA, Zein LH, Zulkhairi, Akil F, Uswan WB, Simanjuntak D, Uchida T, Adi P, Utari AP, Rezkitha YAA, Subsomwong P, Nasronudin, Yamaoka Y. Helicobacter pylori virulence genes in the five largest islands of Indonesia. Gut Pathog 2015; 7:26. [PMID: 26442711 PMCID: PMC4594740 DOI: 10.1186/s13099-015-0072-2] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Accepted: 09/07/2015] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND It remains unclear whether the low incidence of gastric cancer in Indonesia is due to low infection rates only or is also related to low Helicobacter pylori pathogenicity. We collected H. pylori strains from the five largest islands in Indonesia and evaluated genetic virulence factors. METHODS The genotypes of H. pylori virulence factors were determined by polymerase chain reaction (PCR)-based sequencing. Histological severity of the gastric mucosa was classified into 4 grades, according to the updated Sydney system. RESULTS A total of 44 strains were analyzed. Forty-three (97.7 %) were cagA-positive: 26 (60.5 %) were East-Asian-type-cagA, 9 (20.9 %) were Western-type-cagA, and 8 (18.6 %) were novel ABB-type, most of which were obtained from Papuan. EPIYT sequences were more prevalent than EPIYA sequences (P = 0.01) in the EPIYA-B motif of all types of cagA. The majority of cagA-positive strains (48.8 %, 21/43) had a 6-bp deletion in the first pre-EPIYA region. Subjects infected with East-Asian-type-cagA strains with a 6-bp deletion had significantly lower inflammation and atrophy scores in the corpus than those infected with Western-type-cagA strains (both P = 0.02). In total, 70.4 % of strains possessed the vacA s1m1 genotype and 29.5 % were m2. All strains from peptic ulcer patients were of the iceA1 genotype, which occurred at a significantly higher proportion in peptic ulcer patients than that in gastritis patients (55.3 %, P = 0.04). The double positive genotype of jhp0562/β-(1,3)galT was predominant (28/44, 63.6 %), and subjects infected with this type had significantly higher inflammation scores in the corpus than those with the jhp0562 negative/β-(1,3)galT positive genotype (mean [median]; 1.43 [1] vs. 0.83 [1], P = 0.04). There were significant differences in cagA and pre-EPIYA cagA type, oipA status, and jhp0562/β-(1,3)galT type among different ethnic groups (P < 0.05). CONCLUSIONS In addition to a low H. pylori infection rate, the low incidence of gastric cancer in Indonesia might be attributed to less virulent genotypes in predominant strains, which are characterized by the East-Asian-type-cagA with a 6-bp deletion and EPIYT motif, a high proportion of m2, dupA negative or short type dupA, and the jhp0562/β-(1,3)galT double positive genotype.
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Affiliation(s)
- Muhammad Miftahussurur
- />Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5593 Japan
- />Gastroentero-Hepatology Division, Department of Internal Medicine, Airlangga University Faculty of Medicine, Surabaya, 60131 Indonesia
- />Institute of Tropical Disease, Airlangga University, Surabaya, 60115 Indonesia
| | - Ari Fahrial Syam
- />Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, 10430 Indonesia
| | - Dadang Makmun
- />Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, 10430 Indonesia
| | - Iswan Abbas Nusi
- />Gastroentero-Hepatology Division, Department of Internal Medicine, Airlangga University Faculty of Medicine, Surabaya, 60131 Indonesia
| | - Lukman Hakim Zein
- />Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sumatera Utara, Medan, 20136 Indonesia
| | - Zulkhairi
- />Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sumatera Utara, Medan, 20136 Indonesia
| | - Fardah Akil
- />Department of Internal Medicine, Faculty of Medicine, Center of Gastroentero-Hepatology, Hasanuddin University, Makassar, 90245 Indonesia
| | - Willi Brodus Uswan
- />Department of Internal Medicine, Santo Antonius Hospital, Pontianak, 78115 Indonesia
| | - David Simanjuntak
- />Department of Internal Medicine, Yowari Hospital, Jayapura, 99352 Indonesia
| | - Tomohisa Uchida
- />Department of Molecular Pathology, Oita University Faculty of Medicine, Yufu, 879-5593 Japan
| | - Pangestu Adi
- />Institute of Tropical Disease, Airlangga University, Surabaya, 60115 Indonesia
| | - Amanda Pitarini Utari
- />Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, 10430 Indonesia
| | | | - Phawinee Subsomwong
- />Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5593 Japan
| | - Nasronudin
- />Institute of Tropical Disease, Airlangga University, Surabaya, 60115 Indonesia
| | - Yoshio Yamaoka
- />Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5593 Japan
- />Department of Gastroenterology and Hepatology, Baylor College of Medicine and Michael DeBakey Veterans Affairs Medical Center, Houston, TX 77030 USA
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Saraiva-Pava K, Navabi N, Skoog EC, Lindén SK, Oleastro M, Roxo-Rosa M. New NCI-N87-derived human gastric epithelial line after human telomerase catalytic subunit over-expression. World J Gastroenterol 2015; 21:6526-6542. [PMID: 26074691 PMCID: PMC4458763 DOI: 10.3748/wjg.v21.i21.6526] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Revised: 02/07/2015] [Accepted: 03/31/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To establish a cellular model correctly mimicking the gastric epithelium to overcome the limitation in the study of Helicobacter pylori (H. pylori) infection.
METHODS: Aiming to overcome this limitation, clones of the heterogenic cancer-derived NCI-N87 cell line were isolated, by stably-transducing it with the human telomerase reverse-transcriptase (hTERT) catalytic subunit gene. The clones were first characterized regarding their cell growth pattern and phenotype. For that we measured the clones’ adherence properties, expression of cell-cell junctions’ markers (ZO-1 and E-cadherin) and ability to generate a sustained transepithelial electrical resistance. The gastric properties of the clones, concerning expression of mucins, zymogens and glycan contents, were then evaluated by haematoxylin and eosin staining, Periodic acid Schiff (PAS) and PAS/Alcian Blue-staining, immunocytochemistry and Western blot. In addition, we assessed the usefulness of the hTERT-expressing gastric cell line for H. pylori research, by performing co-culture assays and measuring the IL-8 secretion, by ELISA, upon infection with two H. pylori strains differing in virulence.
RESULTS: Compared with the parental cell line, the most promising NCI-hTERT-derived clones (CL5 and CL6) were composed of cells with homogenous phenotype, presented higher relative telomerase activities, better adhesion properties, ability to be maintained in culture for longer periods after confluency, and were more efficient in PAS-reactive mucins secretion. Both clones were shown to produce high amounts of MUC1, MUC2 and MUC13. NCI-hTERT-CL5 mucins were shown to be decorated with blood group H type 2 (BG-H), Lewis-x (Lex), Ley and Lea and, in a less extent, with BG-A antigens, but the former two antigens were not detected in the NCI-hTERT-CL6. None of the clones exhibited detectable levels of MUC6 nor sialylated Lex and Lea glycans. Entailing good gastric properties, both NCI-hTERT-clones were found to produce pepsinogen-5 and human gastric lipase. The progenitor-like phenotype of NCI-hTERT-CL6 cells was highlighted by large nuclei and by the apical vesicular-like distribution of mucin 5AC and Pg5, supporting the accumulation of mucus-secreting and zymogens-chief mature cells functions.
CONCLUSION: These traits, in addition to resistance to microaerobic conditions and good responsiveness to H. pylori co-culture, in a strain virulence-dependent manner, make the NCI-hTERT-CL6 a promising model for future in vitro studies.
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The Prevalence of Helicobacter pylori Virulence Factors in Bhutan, Vietnam, and Myanmar Is Related to Gastric Cancer Incidence. BIOMED RESEARCH INTERNATIONAL 2015; 2015:830813. [PMID: 26090448 PMCID: PMC4450262 DOI: 10.1155/2015/830813] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/04/2014] [Revised: 01/26/2015] [Accepted: 01/31/2015] [Indexed: 12/24/2022]
Abstract
Gastric cancer is a significant health problem in Asia. Although the prevalence of Helicobacter pylori infection is similar in Bhutan, Vietnam, and Myanmar, the incidence of gastric cancer is highest in Bhutan, followed by Vietnam and Myanmar. We hypothesized that H. pylori virulence factors contribute to the differences. The status of cagA, vacA, jhp0562, and β-(1,3)galT(jhp0563) was examined in 371 H. pylori-infected patients from Bhutan, Vietnam, and Myanmar. Each virulence factor could not explain the difference of the incidence of gastric cancer. However, the prevalence of quadruple-positive for cagA, vacA s1, vacA m1, and jhp0562-positive/β-(1,3)galT-negative was significantly higher in Bhutan than in Vietnam and Myanmar and correlated with gastric cancer incidence. Moreover, gastritis-staging scores measured by histology of gastric mucosa were significantly higher in quadruple-positive strains. We suggest that the cagA, vacA s1, vacA m1, and jhp0562-positive/β-(1,3)galT-negative genotype may play a role in the development of gastric cancer.
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Almeida N, Donato MM, Romãozinho JM, Luxo C, Cardoso O, Cipriano MA, Marinho C, Fernandes A, Sofia C. Correlation of Helicobacter pylori genotypes with gastric histopathology in the central region of a South-European country. Dig Dis Sci 2015; 60:74-85. [PMID: 25142169 DOI: 10.1007/s10620-014-3319-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Accepted: 08/01/2014] [Indexed: 12/30/2022]
Abstract
BACKGROUND Outcome of Helicobacter pylori (H. pylori) infection results from interaction of multiple variables including host, environmental and bacterial-associated virulence factors. AIM This study aimed to investigate the correlation of cagA, cagE, vacA, iceA and babA2 genotypes with gastric histopathology and disease phenotype in the central region of a South-European country. METHODS This prospective study involved 148 infected patients (110 female; mean age 43.5 ± 13.4 years) submitted to endoscopy with corpus and antrum biopsies. H. pylori was cultured and DNA extracted from the isolates. Genotypes were determined by PCR. Histopathological features were graded according to the updated Sydney system and OLGA/OLGIM classification. Only patients with single H. pylori genotypes and complete histopathological results were included. RESULTS Antrum samples presented higher degrees of atrophy, intestinal metaplasia, chronic inflammation and neutrophil activity. Genotype distribution was as follows: cagA-31.8 %; cagE-45.9 %; vacA s1a-24.3 %; vacA s1b-19.6 %; vacA s1c-0.7 %; vacA s2-55.4 %; vacA m1-20.9 %; vacA m2-79.1 %; vacA s1m1-18.9 %; vacA s1m2-25.7 %; vacA s2m1-2 %; vacA s2m2-53.4 %; iceA1-33.8 %; iceA2-66.2 %; babA2-12.2 %. CagA genotype was significantly associated with higher degrees of intestinal metaplasia, neutrophil activity, chronic inflammation and OLGIM stages. BabA2 was linked with higher H. pylori density. Strains with vacA s1m1 or vacA s1m1 + cagA positive genotypes had a significant association with peptic ulcer and vacA s2m2 with iron-deficient anemia. CONCLUSIONS cagA, vacA s1m1 and babA2 genotypes are relatively rare in the central region of Portugal. cagA-positive strains are correlated with more severe histopathological modifications. This gene is commonly associated with vacA s1m1, and such isolates are frequently found in patients with peptic ulcer.
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Affiliation(s)
- Nuno Almeida
- Gastroenterology Department, Coimbra University Hospital Centre, Praceta Mota Pinto e Avenida Bissaya Barreto, 3000-075, Coimbra, Portugal,
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Homan M, Šterbenc A, Kocjan BJ, Luzar B, Zidar N, Orel R, Poljak M. Prevalence of the Helicobacter pylori babA2 gene and correlation with the degree of gastritis in infected Slovenian children. Antonie Van Leeuwenhoek 2014; 106:637-645. [PMID: 25055876 DOI: 10.1007/s10482-014-0234-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Accepted: 07/07/2014] [Indexed: 12/16/2022]
Abstract
The aims of our study were to determine the prevalence of the babA2 gene within Helicobacter pylori strains circulating in the Slovenian pediatric population, to further clarify its significance in causing inflammation of gastric mucosa in children and to verify whether cagA, vacA, iceA and babA genes work independently or synergistically in causing gastritis. A total of 163 H. pylori isolates obtained from the same number of children were tested for the presence of cagA, vacA and iceA genes using previously established methods, while the babA2 gene was determined using novel polymerase chain reaction assay targeting a 139-bp fragment of the central region of babA2. The babA2 gene was detected in 47.9% of H. pylori samples. The presence of the babA2 gene was strongly associated with cagA, vacA s1 and vacA m1 genotype. The babA2 status correlated positively with bacterial density score, activity of inflammation and chronic inflammation of gastric mucosa. No significant correlation was found between the babA2 status and the presence of atrophy or intestinal metaplasia. In addition, the activity of gastric inflammation and density score were significantly associated with the coexpression of the cagA, vacA s1, vacA m1 and babA2 genes. The study, which included the largest number of pediatric H. pylori samples to date, confirmed that babA2 gene plays an important role in the pathogenesis of H. pylori gastritis in children. Furthermore, our results suggest that babA2, cagA and vacA s1 and m1 gene products may work synergistically in worsening the inflammation of gastric mucosa.
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Affiliation(s)
- Matjaž Homan
- Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital, Ljubljana, Slovenia,
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Liu J, He C, Chen M, Wang Z, Xing C, Yuan Y. Association of presence/absence and on/off patterns of Helicobacter pylori oipA gene with peptic ulcer disease and gastric cancer risks: a meta-analysis. BMC Infect Dis 2013; 13:555. [PMID: 24256489 PMCID: PMC4225565 DOI: 10.1186/1471-2334-13-555] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2013] [Accepted: 10/18/2013] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND There are increasing studies examining the relationship between the status of H. pylori oipA gene and peptic ulcer disease (PUD) and gastric cancer (GC) but the results turn out to be controversial. We attempted to clarify whether oipA gene status is linked with PUD and/or GC risks. METHODS A systematically literature search was performed through four electronic databases. According to the specific inclusion and exclusion criteria, seven articles were ultimately available for the meta-analysis of oipA presence/absence with PUD and GC, and eleven articles were included for the meta-analysis of oipA on/off status with PUD and GC. RESULTS For the on/off functional status analysis of oipA gene, the "on" status showed significant associations with increased risks of PUD (OR = 3.97, 95% CI: 2.89, 5.45; P < 0.001) and GC (OR = 2.43, 95% CI: 1.45, 4.07; P = 0.001) compared with gastritis and functional dyspepsia controls. Results of the homogeneity test indicated different effects of oipA "on" status on PUD risk between children and adult subgroups and on GC risk between PCR-sequencing and immunoblot subgroups. For the presence/absence analysis of oipA gene, we found null association of the presence of oipA gene with the risks of PUD (OR = 1.93, 95% CI: 0.60, 6.25; P = 0.278) and GC (OR = 2.09, 95% CI: 0.51, 8.66; P = 0.308) compared with gastritis and functional dyspepsia controls. CONCLUSIONS To be concluded, when oipA exists, the functional "on" status of this gene showed association with increased risks for PUD and GC compared with gastritis and FD controls. However, merely investigating the presence/absence of oipA would overlook the importance of its functional on/off status and would not be reliable to predict risks of PUD and GC. Further large-scale and well-designed studies concerning on/off status of oipA are required to confirm our meta-analysis results.
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Affiliation(s)
- Jingwei Liu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China.
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N-glycosidase treatment with 18O labeling and de novo sequencing argues for flagellin FliC glycopolymorphism in Pseudomonas aeruginosa. Anal Bioanal Chem 2013; 405:9835-42. [PMID: 24220757 DOI: 10.1007/s00216-013-7424-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2013] [Revised: 09/27/2013] [Accepted: 10/07/2013] [Indexed: 10/26/2022]
Abstract
In prokaryote organisms, N-glycosylation of proteins is often correlated to cell-cell recognition and extracellular events. Those glycoproteins are potential targets for infection control. To date, many surface-glycosylated proteins from bacterial pathogens have been described. However, N-linked Pseudomonas surface-associated glycoproteins remain underexplored. We report a combined enrichment and labeling strategy to identify major glycoproteins on the outside of microorganisms. More precisely, bacteria were exposed to a mix of biotinylated lectins able to bind with glycoproteins. The latter were then recovered by avidin beads, digested with trypsin, and submitted to mass spectrometry. The targeted mixture of glycoproteins was additionally deglycosylated in the presence of H2(18)O to incorporate (18)O during PNGase F treatment and were also analyzed using mass spectrometry. This approach allowed us to identify a few tens of potential N-glycoproteins, among which flagellin FliC was the most abundant. To detect the possible sites of FliC modifications, a de novo sequencing step was also performed to discriminate between spontaneous deamidation and N-glycan loss. This approach led to the proposal of three potential N-glycosylated sites on the primary sequence of FliC: N26, N69, and N439, with two of these three asparagines belonging to an N-X-(S/T) consensus sequence. These observations suggest that flagellin FliC is a heterogeneous protein mixture containing both O- and N-glycoforms.
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Chen MY, He CY, Meng X, Yuan Y. Association of Helicobacter pylori babA2 with peptic ulcer disease and gastric cancer. World J Gastroenterol 2013; 19:4242-4251. [PMID: 23864790 PMCID: PMC3710429 DOI: 10.3748/wjg.v19.i26.4242] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2013] [Revised: 04/03/2013] [Accepted: 05/17/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the association between babA2 gene and peptic ulcer disease (PUD) and gastric cancer (GC) in Helicobacter pylori-infected populations.
METHODS: We evaluated the relationship between babA2 and clinical outcomes (PUD and GC) using a meta-analysis. A literature search was performed using the PubMed and Web of Science databases for relevant case-control studies that met the defined inclusion criteria. The ORs and 95%CIs were calculated to estimate the association between babA2 genotype and clinical outcomes. A fixed-effect or random-effect model was performed depending on the absence or presence of significant heterogeneity.
RESULTS: A total of 25 articles with 38 studies met the inclusion criteria and were finally included in this meta-analysis. The results showed that the babA2 genotype was significantly associated with an increased risk of PUD (OR = 2.069, 95%CI: 1.530-2.794, P < 0.001) and especially in the subgroup of duodenal ulcer (OR = 1.588, 95%CI: 1.141-2.209, P = 0.006). Moreover, a significant association between babA2 gene and PUD and duodenal ulcer (OR = 2.739, 95%CI: 1.860-4.032, P < 0.001; OR = 2.239, 95%CI: 1.468-3.415, P < 0.001, respectively) was observed in western countries but not in Asian countries.
CONCLUSION: We demonstrated that the presence of babA2 may be associated with increased risks for PUD, especially duodenal ulcer, in western countries.
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Altman E, Chandan V, Harrison BA, Panayotopoulou EG, Roma-Giannikou E, Li J, Sgouras DN. Helicobacter pylori isolates from Greek children express type 2 and type 1 Lewis and α1,6-glucan antigens in conjunction with a functional type IV secretion system. J Med Microbiol 2012; 61:559-566. [DOI: 10.1099/jmm.0.038729-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Affiliation(s)
- Eleonora Altman
- Institute for Biological Sciences, National Research Council Canada, Ottawa, ON K1A 0R6, Canada
| | - Vandana Chandan
- Institute for Biological Sciences, National Research Council Canada, Ottawa, ON K1A 0R6, Canada
| | - Blair A. Harrison
- Institute for Biological Sciences, National Research Council Canada, Ottawa, ON K1A 0R6, Canada
| | | | | | - Jianjun Li
- Institute for Biological Sciences, National Research Council Canada, Ottawa, ON K1A 0R6, Canada
| | - Dionyssios N. Sgouras
- Laboratory of Medical Microbiology, Hellenic Pasteur Institute, Athens 11521, Greece
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Sicinschi LA, Correa P, Bravo LE, Peek RM, Wilson KT, Loh JT, Yepez MC, Gold BD, Thompson DT, Cover TL, Schneider BG. Non-invasive genotyping of Helicobacter pylori cagA, vacA, and hopQ from asymptomatic children. Helicobacter 2012; 17:96-106. [PMID: 22404439 PMCID: PMC3305281 DOI: 10.1111/j.1523-5378.2011.00919.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Helicobacter pylori infection is usually acquired in childhood, but little is known about its natural history in asymptomatic children, primarily due to the paucity of non-invasive diagnostic methods. H. pylori strains harboring cagA and specific alleles of hopQ and vacA are associated with increased risk for gastric cancer. Many studies of H. pylori virulence markers in children have the bias that symptomatic subjects are selected for endoscopy, and these children may harbor the most virulent strains. Our aim is to genotype cagA, hopQ, and vacA alleles in stool DNA samples of healthy Colombian children residing in an area with high incidence of gastric cancer, to avoid selection bias resulting from endoscopy. METHODS H. pylori status of 86 asymptomatic children was assessed by (13) C-urea breath test (UBT) and PCR. H. pylori 16S rRNA, cagA, hopQ, and vacA genes were amplified from stool DNA samples and sequenced. RESULTS UBT was positive in 69 (80.2%) of 86 children; in stool DNA analysis, 78.3% were positive by 16S rRNA PCR. cagA, vacA, and hopQ were detected in 66.1%, 84.6%, and 72.3% of stool DNA samples from 16S rRNA-positive children. Of the children's DNA samples, which revealed vacA and hopQ alleles, 91.7% showed vacA s1 and 73.7% showed type I hopQ. Type I hopQ alleles were associated with cagA positivity and vacA s1 genotypes (p < 0.0001). CONCLUSIONS Using stool DNA samples, virulence markers of H. pylori were successfully genotyped in a high percentage of the asymptomatic infected children, revealing a high prevalence of genotypes associated with virulence. Type I hopQ alleles were associated with the presence of cagA and the vacA s1 genotype.
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Affiliation(s)
- Liviu A. Sicinschi
- Division of Gastroenterology, Dept. of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232,Department of Microbiology and Immunology, Holmes Regional Medical Center, Melbourne, FL 32901, USA
| | - Pelayo Correa
- Division of Gastroenterology, Dept. of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232
| | - Luis E. Bravo
- Department of Pathology, School of Medicine, Universidad del Valle, Pasto, Colombia
| | - Richard M. Peek
- Division of Gastroenterology, Dept. of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232
| | - Keith T. Wilson
- Division of Gastroenterology, Dept. of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232,Veterans Affairs Tennessee Valley Health Care System, Nashville, TN 37212, USA
| | - John T. Loh
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
| | - Maria C. Yepez
- Centro de Estudios de Salud, Universidad de Nariño, Pasto, Colombia
| | - Benjamin D. Gold
- Children's Center for Digestive Healthcare, Pediatric Gastroenterology, Hepatology and Nutrition, Atlanta, GA 30342
| | - Dexter T. Thompson
- Division of Gastroenterology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Timothy L. Cover
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA,Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA,Veterans Affairs Tennessee Valley Health Care System, Nashville, TN 37212, USA
| | - Barbara G. Schneider
- Division of Gastroenterology, Dept. of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232
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Novel functions for glycosyltransferases Jhp0562 and GalT in Lewis antigen synthesis and variation in Helicobacter pylori. Infect Immun 2012; 80:1593-605. [PMID: 22290141 DOI: 10.1128/iai.00032-12] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Lewis (Le) antigens are fucosylated oligosaccharides present in the Helicobacter pylori lipopolysaccharide. Expression of these antigens is believed to be important for H. pylori colonization, since Le antigens also are expressed on the gastric epithelia in humans. A galactosyltransferase encoded by β-(1,3)galT is essential for production of type 1 (Le(a) and Le(b)) antigens. The upstream gene jhp0562, which is present in many but not all H. pylori strains, is homologous to β-(1,3)galT but is of unknown function. Because H. pylori demonstrates extensive intragenomic recombination, we hypothesized that these two genes could undergo DNA rearrangement. A PCR screen and subsequent sequence analyses revealed that the two genes can recombine at both the 5' and 3' ends. Chimeric β-(1,3)galT-like alleles can restore function in a β-(1,3)galT null mutant, but neither native nor recombinant jhp0562 can. Mutagenesis of jhp0562 revealed that it is essential for synthesis of both type 1 and type 2 Le antigens. Transcriptional analyses of both loci showed β-(1,3)galT expression in all wild-type (WT) and mutant strains tested, whereas jhp0562 was not expressed in jhp0562 null mutants, as expected. Since jhp0562 unexpectedly displayed functions in both type 1 and type 2 Le synthesis, we asked whether galT, part of the type 2 synthesis pathway, had analogous functions in type 1 synthesis. Mutagenesis and complementation analysis confirmed that galT is essential for Le(b) production. In total, these results demonstrate that galT and jhp0562 have functions that cross the expected Le synthesis pathways and that jhp0562 provides a substrate for intragenomic recombination to generate diverse Le synthesis enzymes.
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Pohl MA, Zhang W, Shah SN, Sanabria-Valentín EL, Perez-Perez GI, Blaser MJ. Genotypic and phenotypic variation of Lewis antigen expression in geographically diverse Helicobacter pylori isolates. Helicobacter 2011; 16:475-81. [PMID: 22059399 PMCID: PMC3228314 DOI: 10.1111/j.1523-5378.2011.00897.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Helicobacter pylori are a persistent colonizer of the human gastric mucosa, which can lead to the development of peptic ulcer disease and gastric adenocarcinomas. However, H. pylori can asymptomatically colonize a host for years. One factor that has been hypothesized to contribute to such persistence is the production of Lewis (Le) antigens in the lipopolysaccharide layer of the bacterial outer membrane as a form of molecular mimicry, because humans also express these antigens on their gastric mucosa. Humans and H. pylori both are polymorphic for Le expression, which is driven in H. pylori by variation at the Le synthesis loci. In this report, we sought to characterize Le genotypic and phenotypic variation in geographically diverse H. pylori isolates. MATERIALS AND METHODS From patients undergoing endoscopy in 29 countries, we determined Le phenotypes of 78 H. pylori strains and performed genotyping of the galT and β-(1,3)galT loci in 113 H. pylori strains. RESULTS Le antigen phenotyping revealed a significant (p < .0001) association between type 1 (Le(a) and Le(b) ) expression and strains of East Asian origin. Genotyping revealed a significant correlation between strain origin and the size of the promoter region upstream of the Le synthesis gene, galT (p < .0001). CONCLUSION These results indicate that the heterogeneity of human Le phenotypes is reflected in their H. pylori colonizing strains and suggest new loci that can be studied to assess the variation of Le expression.
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Affiliation(s)
- Mary Ann Pohl
- Department of Medicine, New York University School of Medicine, New York, NY, USA.
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Vitoriano I, Saraiva-Pava KD, Rocha-Gonçalves A, Santos A, Lopes AI, Oleastro M, Roxo-Rosa M. Ulcerogenic Helicobacter pylori strains isolated from children: a contribution to get insight into the virulence of the bacteria. PLoS One 2011; 6:e26265. [PMID: 22039453 PMCID: PMC3198394 DOI: 10.1371/journal.pone.0026265] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2011] [Accepted: 09/23/2011] [Indexed: 12/15/2022] Open
Abstract
Infection with Helicobacter pylori is the major cause for the development of peptic ulcer disease (PUD). In children, with no other etiology for the disease, this rare event occurs shortly after infection. In these young patients, habits of smoking, diet, consumption of alcohol and non-steroid anti-inflammatory drugs and stress, in addition to the genetic susceptibility of the patient, represent a minor influence. Accordingly, the virulence of the implicated H. pylori strain should play a crucial role in the development of PUD. Corroborating this, our in vitro infection assays comparing a pool of five H. pylori strains isolated from children with PUD to a pool of five other pediatric clinical isolates associated with non-ulcer dyspepsia (NUD) showed the greater ability of PUD strains to induce a marked decrease in the viability of gastric cells and to cause severe damage in the cells cytoskeleton as well as an impairment in the production/secretion of mucins. To uncover virulence features, we compared the proteome of these two groups of H. pylori strains. Two-dimensional gel electrophoresis followed by mass-spectrometry allowed us to detect 27 differentially expressed proteins between them. In addition to the presence of genes encoding well established virulence factors, namely cagA, vacAs1, oipA “on” status, homB and jhp562 genes, the pediatric ulcerogenic strains shared a proteome profile characterized by changes in the abundance of: motility-associated proteins, accounting for higher motility; antioxidant proteins, which may confer increased resistance to inflammation; and enzymes involved in key steps in the metabolism of glucose, amino acids and urea, which may be advantageous to face fluctuations of nutrients. In conclusion, the enhanced virulence of the pediatric ulcerogenic H. pylori strains may result from a synergy between their natural ability to better adapt to the hostile human stomach and the expression of the established virulence factors.
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Affiliation(s)
- Inês Vitoriano
- Faculdade de Engenharia, Universidade Católica Portuguesa, Rio de Mouro, Portugal
| | | | | | - Andrea Santos
- Departamento de Doenças Infecciosas, Instituto Nacional Saúde Dr. Ricardo Jorge, Lisboa, Portugal
| | - Ana I. Lopes
- Departamento de Pediatria, Hospital Universitário de Santa Maria/Faculdade de Medicina de Lisboa, Lisboa, Portugal
| | - Mónica Oleastro
- Departamento de Doenças Infecciosas, Instituto Nacional Saúde Dr. Ricardo Jorge, Lisboa, Portugal
| | - Mónica Roxo-Rosa
- Faculdade de Engenharia, Universidade Católica Portuguesa, Rio de Mouro, Portugal
- * E-mail:
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Matsuda M, Shiota S, Matsunari O, Watada M, Murakami K, Fujioka T, Yamaoka Y. Prevalence of two homologous genes encoding glycosyltransferases of Helicobacter pylori in the United States and Japan. J Gastroenterol Hepatol 2011; 26:1451-6. [PMID: 21592227 PMCID: PMC3166395 DOI: 10.1111/j.1440-1746.2011.06779.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIM jhp0562 and β-(1,3)galT (jhp0563) of Helicobacter pylori have been suggested as novel virulent factors; however, the clinical associations and functions of these genes remain unclear. We examined the prevalence of jhp0562, β-(1,3)galT, and cagA in the United States (US) and Japanese populations. METHODS A total of 308 strains (171 from the US and 137 from Japan) were examined for the status of jhp0562, β-(1,3)galT, and cagA by polymerase chain reaction. RESULTS There were significant differences in the status of jhp0562, β-(1,3)galT and cagA between the US and Japanese populations (P < 0.001). In the US, the prevalence of β-(1,3)galT was significantly lower in strains isolated from patients with duodenal ulcer (DU) or gastric ulcer (GU) than those with gastritis (47.8% and 32.1% vs 72.0%, P < 0.01), and the absence of β-(1,3)galT was an independent factor discriminating DU and GU from gastritis (adjusted odds ratios, 4.21 and 8.52; 95% confidence intervals, 1.75 to 10.12 and 2.76 to 26.33, respectively). In the US, the prevalence of the jhp0562-positive/β-(1,3)galT-negative genotype was significantly higher in strains from DU and GU patients than in those from gastritis patients (50.0%, 67.9%, and 24.4%, P < 0.01) and the cagA status was significantly correlated with that of jhp0562 and inversely correlated with that of β-(1,3)galT. In contrast, the prevalence of these three genes was not significantly different in Japan. CONCLUSIONS jhp0562 or β-(1,3)galT can be used to discriminate peptic ulcers from gastritis in the US, but not in Japan.
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Affiliation(s)
- Miyuki Matsuda
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan
| | - Seiji Shiota
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan,Department of General Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan
| | - Osamu Matsunari
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan,Department of General Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan
| | - Masahide Watada
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan,Department of General Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan
| | - Kazunari Murakami
- Department of General Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan
| | - Toshio Fujioka
- Department of General Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan,Department of Medicine-Gastroenterology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Blvd. Houston, Texas 77030, United States
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Abstract
This article reviewed the important publications on Helicobacter pylori research with children between April 2010 and March 2011. The most interesting studies in the last year lend further weight to the evidence for vertical transmission of H. pylori. The discovery of a potential role for jhp0562, the gene which encodes for the cell envelope protein glycosyltransferase, in the progression to peptic ulcer disease is also very interesting as it may provide a novel way to distinguish children at risk of peptic ulcer disease from those who are not, and so determine those who requires treatment to eradicate H. pylori. The rise in non-H. pylori-associated ulcers and erosions continues to be reported with no apparent risk factors for these ulcers identified to date. High levels of treatment failure continue to be reported, and there remains an urgent need for more effective treatment regimes for children.
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Affiliation(s)
- Josef Sýkora
- Department of Paediatrics, Charles University in Prague, Faculty of Medicine in Pilsen, Faculty Hospital, Pilsen, Czech Republic.
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