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Helicobacter pylori Research

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 August 2018) | Viewed by 34326

Special Issue Editors

1. Department of Medicine-Gastroenterology, Baylor College of Medicine, Houston, TX, USA
2. Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Japan
Interests: Helicobacter pylori; gastric cancer; virulence factors; epidemiology; human migration; antibiotics resistance; signal pathways; next genration sequencing
Special Issues, Collections and Topics in MDPI journals
Department of Internal Medicine, College of Medicine, National Taiwan University, No 7, Chung-Shan S Road, Taipei , Taiwan
Interests: Helicobacter pylori; gastric cancer; gastroenterology; molecular biology; antibiotics resistance; eradication therapy

Special Issue Information

Dear Colleagues,

Helicobacter pylori is still the central focus for many researchers since it was discovered in 1982. This ubiquitous bacterium is etiologically associated to a very large spectrum of diseases, ranging from gastritis to gastric cancer. Although the incidence and mortality of gastric cancer has declined recently, mainly due to H. pylori eradication campaigns, gastric cancer is still a significant public health issue worldwide. Generally acquired in childhood, the infection persists throughout life unless treated. H. pylori is also considered the most diverse pathogenic bacteria, with a well-structural genetic diversity, that, in turn, can be used as a tool to dig into past human history. Although many resources have been used for the understanding of the biology of this bacterium and its relationship with the human host, the colonization mechanisms are still unclear, as is the interaction of the host-bacterial virulence-environment, determination of antibiotic resistance patterns, and the molecular mechanisms for cellular signaling pathways. This Special Issue will center on both reviews and original papers that focus on defining: (1) molecular mechanisms encountered in the pathogenesis of H. pylori; (2) molecular epidemiology of virulence factors for the inference of disease outcomes and new targets for eradication treatment; and (3) molecular evolution and population structure of bacteria.

Prof. Yoshio Yamaoka
Prof. Ming-Shiang Wu
Guest Editors

Manuscript Submission Information

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Keywords

  • Helicobacter pylori
  • gastric cancer
  • virulence factors
  • epidemiology
  • human migration
  • antibiotics resistance
  • eradication therapy
  • signal pathways
  • next genration sequencing

Published Papers (7 papers)

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Research

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11 pages, 818 KiB  
Article
Combined Gastric and Colorectal Cancer Screening—A New Strategy
by Michael Selgrad, Jan Bornschein, Arne Kandulski, Jochen Weigt, Albert Roessner, Thomas Wex and Peter Malfertheiner
Int. J. Mol. Sci. 2018, 19(12), 3854; https://doi.org/10.3390/ijms19123854 - 03 Dec 2018
Cited by 13 | Viewed by 3510
Abstract
Background: Our aim was to evaluate the feasibility of a serological assessment of gastric cancer risk in patients undergoing colonoscopy in countries with low-to-moderate incidence rates. Methods: Serum samples were prospectively collected from 453 patients (>50 years old) undergoing colonoscopies. Of these, 279 [...] Read more.
Background: Our aim was to evaluate the feasibility of a serological assessment of gastric cancer risk in patients undergoing colonoscopy in countries with low-to-moderate incidence rates. Methods: Serum samples were prospectively collected from 453 patients (>50 years old) undergoing colonoscopies. Of these, 279 (61.6%) also underwent gastroscopy to correlate the results for serum pepsinogen I and II (sPG-I and sPG-II), sPG-I/II ratio, and anti-H. pylori antibodies with gastric histopathology findings (graded according to the updated Sydney classification and the Operative Link of Gastritis Assessment (OLGA) and the Operative Link for Gastric Intestinal Metaplasia assessment (OLGIM) systems). Results: H. pylori was found in 85 patients (30.5%). Chronic atrophic gastritis was diagnosed in 89 (31.9%) patients. High-risk OLGA (III–IV) stages were present in 24 patients, and high-risk OLGIM stages were present in 14 patients. There was an inverse correlation of sPG-I with the degree of atrophy and intestinal metaplasia (IM), as well as with the respective OLGA (r = −0.425; p < 0.001) and OLGIM (r = −0.303; p < 0.001) stages. A pathological sPG-I result was associated with a relative risk (RR) of 12.2 (95% confidence interval: 6.29–23.54; p < 0.001) for gastric preneoplastic changes. Conclusions: The assessment of serum pepsinogen allows the identification of patients at increased risk of gastric cancer. A prevention strategy of combining a screening colonoscopy with a serological screening for preneoplastic gastric changes should be considered in the general population. Full article
(This article belongs to the Special Issue Helicobacter pylori Research)
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18 pages, 2576 KiB  
Article
SUMOs Mediate the Nuclear Transfer of p38 and p-p38 during Helicobacter Pylori Infection
by Pin Yao Wang, Ping I. Hsu, Deng Chyang Wu, Te Chung Chen, Andrew Paul Jarman, Lynn Marie Powell and Angela Chen
Int. J. Mol. Sci. 2018, 19(9), 2482; https://doi.org/10.3390/ijms19092482 - 22 Aug 2018
Cited by 12 | Viewed by 4142
Abstract
The p38 mitogen activated protein kinase (MAPK) signaling pathway has been suggested to play a significant role in the gastric mucosal inflammatory response to chronic Helicobacter pylori (H. pylori) infection. Nuclear translocation is thought to be important for p38 function, but [...] Read more.
The p38 mitogen activated protein kinase (MAPK) signaling pathway has been suggested to play a significant role in the gastric mucosal inflammatory response to chronic Helicobacter pylori (H. pylori) infection. Nuclear translocation is thought to be important for p38 function, but no nuclear translocation signals have been found in the protein and no nuclear carrier proteins have been identified for p38. We have investigated the role of small ubiquitin-related modifier (SUMO) in the nuclear transfer of p38 in response to H. pylori infection. Exposure of human AGS cells to H. pylori induced the activation of p38 and the expression of SUMOs, especially SUMO-2. SUMO knockdown counteracted the effect of H. pylori infection by decreasing the resulting p38 mediated cellular apoptosis through a reduction in the nuclear fraction of phosphorylated p38. We identified a non-covalent interaction between SUMOs and p38 via SUMO interaction motifs (SIMs), and showed that SUMO-dependent nuclear transfer of p38 was decreased upon mutation of its SIMs. This study has identified a new pathway of p38 nuclear translocation, in response to H. pylori infection. We conclude that in the presence of H. pylori SUMO-2 has a major role in regulating nuclear levels of p38, through non-covalent SUMO-p38 interactions, independent of the p38 phosphorylation state. Full article
(This article belongs to the Special Issue Helicobacter pylori Research)
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13 pages, 927 KiB  
Article
Molecular Epidemiology of Helicobacter pylori Infection in a Minor Ethnic Group of Vietnam: A Multiethnic, Population-Based Study
by Tran Thanh Binh, Vo Phuoc Tuan, Ho Dang Quy Dung, Pham Huu Tung, Tran Dinh Tri, Ngo Phuong Minh Thuan, Le Quang Tam, Bui Chi Nam, Do Anh Giang, Phan Quoc Hoan, Tomohisa Uchida, Tran Thi Huyen Trang, Vu Van Khien and Yoshio Yamaoka
Int. J. Mol. Sci. 2018, 19(3), 708; https://doi.org/10.3390/ijms19030708 - 01 Mar 2018
Cited by 23 | Viewed by 6686
Abstract
The Helicobacter pylori-induced burden of gastric cancer varies based on geographical regions and ethnic grouping. Vietnam is a multiethnic country with the highest incidence of gastric cancer in Southeast Asia, but previous studies focused only on the Kinh ethnic group. A population-based [...] Read more.
The Helicobacter pylori-induced burden of gastric cancer varies based on geographical regions and ethnic grouping. Vietnam is a multiethnic country with the highest incidence of gastric cancer in Southeast Asia, but previous studies focused only on the Kinh ethnic group. A population-based cross-sectional study was conducted using 494 volunteers (18–78 years old), from 13 ethnic groups in Daklak and Lao Cai provinces, Vietnam. H. pylori status was determined by multiple tests (rapid urease test, culture, histology, and serology). cagA and vacA genotypes were determined by PCR-based sequencing. The overall H. pylori infection rate was 38.1%. Multivariate analysis showed that variations in geographical region, age, and ethnicity were independent factors associated with the risk of H. pylori acquisition. Therefore, multicenter, multiethnic, population based study is essential to assess the H. pylori prevalence and its burden in the general population. Only the E De ethnicity carried strains with Western-type CagA (82%) and exhibited significantly lower gastric mucosal inflammation compared to other ethnic groups. However, the histological scores of Western-type CagA and East-Asian-type CagA within the E De group showed no significant differences. Thus, in addition to bacterial virulence factors, host factors are likely to be important determinants for gastric mucosal inflammation and contribute to the Asian enigma. Full article
(This article belongs to the Special Issue Helicobacter pylori Research)
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10 pages, 238 KiB  
Article
The Prevalence of Helicobacter pylori in Estonian Bariatric Surgery Patients
by Natalja Šebunova, Jelena Štšepetova, Toomas Sillakivi and Reet Mändar
Int. J. Mol. Sci. 2018, 19(2), 338; https://doi.org/10.3390/ijms19020338 - 24 Jan 2018
Cited by 10 | Viewed by 3642
Abstract
Helicobacter pylori (Hp) is one of the most important human pathogens that can cause duodenal and gastric ulcers, gastritis and stomach cancer. Hp infection is considered to be a cause of limiting access to bariatric surgery. The aim of this study [...] Read more.
Helicobacter pylori (Hp) is one of the most important human pathogens that can cause duodenal and gastric ulcers, gastritis and stomach cancer. Hp infection is considered to be a cause of limiting access to bariatric surgery. The aim of this study was to determine the prevalence of Hp in patients with obesity going into bariatric surgery and to reveal the relationship between Hp and clinical data. The study group was formed of 68 preoperative bariatric surgery patients (body mass index (BMI) 44.7 ± 4.8). Gastric biopsies (antrum and corpus) were used for histological and molecular (caqA and glmM genes) examinations. The PCR method revealed Hp infection in 64.7% of obese patients that is higher in comparison with histological analysis (55.9%). The prevalence of cagA and glmM genes in antrum mucosa was 45.6% and 47.0% while in the corpus it was 41.2% and 38.3%, respectively. The coincidence of both cagA and glmM virulence genes in the antrum and corpus mucosa was 33.8% and 22.1%, respectively. Either of the genes was found in 58.8% of antrum and 57.3% of corpus mucosa. Presence of caqA and glmM genes was in association with active and atrophic chronic gastritis. In conclusion, our study demonstrated that two thirds of morbidly obese patients undergoing bariatric surgery are infected with Hp and have a high prevalence of cagA and glmM virulence genes that points out the necessity for diagnostics and treatment of this infection before surgery. Full article
(This article belongs to the Special Issue Helicobacter pylori Research)

Review

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14 pages, 2994 KiB  
Review
Relating Phage Genomes to Helicobacter pylori Population Structure: General Steps Using Whole-Genome Sequencing Data
by Filipa F. Vale and Philippe Lehours
Int. J. Mol. Sci. 2018, 19(7), 1831; https://doi.org/10.3390/ijms19071831 - 21 Jun 2018
Cited by 12 | Viewed by 5220
Abstract
The review uses the Helicobacter pylori, the gastric bacterium that colonizes the human stomach, to address how to obtain information from bacterial genomes about prophage biology. In a time of continuous growing number of genomes available, this review provides tools to explore [...] Read more.
The review uses the Helicobacter pylori, the gastric bacterium that colonizes the human stomach, to address how to obtain information from bacterial genomes about prophage biology. In a time of continuous growing number of genomes available, this review provides tools to explore genomes for prophage presence, or other mobile genetic elements and virulence factors. The review starts by covering the genetic diversity of H. pylori and then moves to the biologic basis and the bioinformatics approaches used for studding the H. pylori phage biology from their genomes and how this is related with the bacterial population structure. Aspects concerning H. pylori prophage biology, evolution and phylogeography are discussed. Full article
(This article belongs to the Special Issue Helicobacter pylori Research)
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13 pages, 4109 KiB  
Review
The Interplay between Two Transcriptional Repressors and Chaperones Orchestrates Helicobacter pylori Heat-Shock Response
by Davide Roncarati and Vincenzo Scarlato
Int. J. Mol. Sci. 2018, 19(6), 1702; https://doi.org/10.3390/ijms19061702 - 07 Jun 2018
Cited by 10 | Viewed by 4879
Abstract
The ability to gauge the surroundings and modulate gene expression accordingly is a crucial feature for the survival bacterial pathogens. In this respect, the heat-shock response, a universally conserved mechanism of protection, allows bacterial cells to adapt rapidly to hostile conditions and to [...] Read more.
The ability to gauge the surroundings and modulate gene expression accordingly is a crucial feature for the survival bacterial pathogens. In this respect, the heat-shock response, a universally conserved mechanism of protection, allows bacterial cells to adapt rapidly to hostile conditions and to survive during environmental stresses. The important and widespread human pathogen Helicobacter pylori enrolls a collection of highly conserved heat-shock proteins to preserve cellular proteins and to maintain their homeostasis, allowing the pathogen to adapt and survive in the hostile niche of the human stomach. Moreover, various evidences suggest that some chaperones of H. pylori may play also non-canonical roles as, for example, in the interaction with the extracellular environment. In H. pylori, two dedicated transcriptional repressors, named HspR and HrcA, homologues to well-characterized regulators found in many other bacterial species, orchestrate the regulation of heat-shock proteins expression. Following twenty years of intense research, characterized by molecular, as well as genome-wide, approaches, it is nowadays possible to appreciate the complex picture representing the heat-shock regulation in H. pylori. Specifically, the HspR and HrcA repressors combine to control the transcription of target genes in a way that the HrcA regulon results embedded within the HspR regulon. Moreover, an additional level of control of heat-shock genes’ expression is exerted by a posttranscriptional feedback regulatory circuit in which chaperones interact and modulate HspR and HrcA DNA-binding activity. This review recapitulates our understanding of the roles and regulation of the most important heat-shock proteins of H. pylori, which represent a crucial virulence factor for bacterial infection and persistence in the human host. Full article
(This article belongs to the Special Issue Helicobacter pylori Research)
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Other

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13 pages, 6948 KiB  
Case Report
Unusual Manifestation of Live Staphylococcus saprophyticus, Corynebacterium urinapleomorphum, and Helicobacter pylori in the Gallbladder with Cholecystitis
by Steffen Backert, Nicole Tegtmeyer, Omar A. Oyarzabal, Dana Osman, Manfred Rohde, Robert Grützmann and Michael Vieth
Int. J. Mol. Sci. 2018, 19(7), 1826; https://doi.org/10.3390/ijms19071826 - 21 Jun 2018
Cited by 8 | Viewed by 4750
Abstract
Culture-independent studies have identified DNA of bacterial pathogens in the gallbladder under pathological conditions, yet reports on the isolation of corresponding live bacteria are rare. Thus, it is unclear which pathogens, or pathogen communities, can colonize the gallbladder and cause disease. Using light [...] Read more.
Culture-independent studies have identified DNA of bacterial pathogens in the gallbladder under pathological conditions, yet reports on the isolation of corresponding live bacteria are rare. Thus, it is unclear which pathogens, or pathogen communities, can colonize the gallbladder and cause disease. Using light microscopy, scanning electron microscopy, culture techniques, phylogenetic analysis, urease assays and Western blotting, we investigated the presence of live bacterial communities in the gallbladder of a cholecystitis patient after cholecystectomy. 16S rRNA gene sequencing of isolated bacterial colonies revealed the presence of pathogens most closely resembling Corynebacterium urinapleomorphum nov. sp., Staphylococcus saprophyticus and Helicobacter pylori. The latter colonies were confirmed as H. pylori by immunohistochemistry and biochemical methods. H. pylori cultured from the gallbladder exhibited both the same DNA fingerprinting and Western cagA gene sequence with ABC-type EPIYA (Glu-Pro-Ile-Tyr-Ala) phosphorylation motifs as isolates recovered from the gastric mucus of the same patient, suggesting that gastric H. pylori can also colonize other organs in the human body. Taken together, here we report, for the first time, the identification and characterization of a community consisting of live S. saprophyticus; C. urinapleomorphum, and H. pylori in the gallbladder of a patient with acute cholecystitis. Their potential infection routes and roles in pathogenesis are discussed. Full article
(This article belongs to the Special Issue Helicobacter pylori Research)
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