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Li J, Jin J, Wang X, Huang F, Sun K, Li M, Liu X. Emerging trends and hotspots in peptic ulcer from 2008 to 2023: A bibliometric analysis. Medicine (Baltimore) 2024; 103:e39557. [PMID: 39252241 PMCID: PMC11383261 DOI: 10.1097/md.0000000000039557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 08/14/2024] [Indexed: 09/11/2024] Open
Abstract
Peptic ulcer (PU) is a common digestive disorder in the gastroduodenal. Although bibliometrics has become very popular in the medical field, a bibliometric analysis of research related to PU has yet to be reported. Therefore, this research aims to analyze the trends and hotspots of PU in the last 15 years. Literature data related to PU retrieved from the Web of Science Core Collection database from 2008 to 2023 were visualized and analyzed using CiteSpace 6.1.6.msi, VOSviewer 1.6.19, and SCImago Graphica Beta 1.0.35. Six thousand four hundred ninety-one papers were collected based on inclusion and exclusion criteria. The country with the highest number of publications was China. The institution with the highest number of publications was Baylor College of Medicine. The most prolific author was Yamaoka Yoshio. Malfertheiner Peter had the highest number of citations. The journal with the most publications is World Journal of Gastroenterology. The most cited Journal is Gastroenterology. The most cited reference was published by Marshall B. J. et al in 1984. The article with the highest burst strength was published in 2012 by Malfertheiner Peter. The keyword with the highest burst strength was "oxidative stress." Our research provides a bibliometric analysis of PU research to reveal the trends and hotspots of PU for 2008 to 2023. Our findings will help researchers to quickly understand the current state of research and provide a reference for in-depth studies in this area to foster the development of PU research.
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Affiliation(s)
- Jiahui Li
- Haiyan Hospital of Traditional Chinese Medicine, Jiaxing, China
| | - Jiamei Jin
- The Basic Medical College of Zhejiang Chinese Medical University, Hangzhou, China
| | - Xiaoyang Wang
- The Basic Medical College of Zhejiang Chinese Medical University, Hangzhou, China
| | - Fugang Huang
- First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Ke Sun
- First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Menglin Li
- First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xiaogu Liu
- The Basic Medical College of Zhejiang Chinese Medical University, Hangzhou, China
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Shirani M, Shariati S, Bazdar M, Sojoudi Ghamnak F, Moradi M, Shams Khozani R, Taki E, Arabsorkhi Z, Heidary M, Eskandari DB. The immunopathogenesis of Helicobacter pylori-induced gastric cancer: a narrative review. Front Microbiol 2024; 15:1395403. [PMID: 39035439 PMCID: PMC11258019 DOI: 10.3389/fmicb.2024.1395403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 05/06/2024] [Indexed: 07/23/2024] Open
Abstract
Helicobacter pylori infection is a well-established risk factor for the development of gastric cancer (GC). Understanding the immunopathogenesis underlying this association is crucial for developing effective preventive and therapeutic strategies. This narrative review comprehensively explores the immunopathogenesis of H. pylori-induced GC by delving into several key aspects, emphasizing the pivotal roles played by H. pylori virulence factors, including cytotoxin-associated gene A (cagA) and vacuolating cytotoxin A (vacA), blood group antigen-binding adhesin (babA), and sialic acid binding adhesin (sabA). Moreover, the review focuses on the role of toll-like receptors (TLRs) and cytokines in the complex interplay between chronic infection and gastric carcinogenesis. Finally, the study examines the association between H. pylori evasion of the innate and adaptive immune response and development of GC. A comprehensive understanding of the immunopathogenesis of H. pylori-induced GC is essential for designing targeted interventions to prevent and manage this disease. Further research is warranted to elucidate the intricate immune responses involved and identify potential therapeutic targets to improve patient outcomes.
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Affiliation(s)
- Maryam Shirani
- Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Saeedeh Shariati
- Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Monireh Bazdar
- School of Medicine, Razi Hospital, Ilam University of Medical Sciences, Ilam, Iran
| | | | - Melika Moradi
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Elahe Taki
- Department of Microbiology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Zahra Arabsorkhi
- Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Mohsen Heidary
- Department of Laboratory Sciences, School of Paramedical Sciences, Sabzevar University of Medical Sciences, Sabzevar, Iran
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Lim B, Kim KS, Ahn JY, Na K. Overcoming antibiotic resistance caused by genetic mutations of Helicobacter pylori with mucin adhesive polymer-based therapeutics. Biomaterials 2024; 308:122541. [PMID: 38547832 DOI: 10.1016/j.biomaterials.2024.122541] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 02/22/2024] [Accepted: 03/19/2024] [Indexed: 05/03/2024]
Abstract
Herein, we describe the 3'-sialyllactose-polyethyleneimine-chlorine e6 conjugate (3PC), meticulously engineered to effectively target Helicobacter bacteria (H. pylori) within the gastric environment. The composition of 3PC comprises polyethyleneimine, a cationic polymer, 3'-sialyllactose, which exhibits a specific binding affinity for H. pylori surface proteins, and a photosensitizer capable of generating oxygen radicals in response to specific wavelengths. The distinctive feature of 3PC lies in its capacity to enhance interaction with the anionic mucus layer facilitated by electrostatic forces. This interaction results in prolonged residence within the intestinal environment. The extended vacation in the intestinal milieu overcomes inherent limitations that have historically impeded conventional antibiotics from efficiently reaching and targeting H. pylori. 3PC can be harnessed as a potent tool for antibacterial photodynamic therapy, and its versatility extends to addressing the challenges posed by various antibiotic-resistant strains. The exceptional efficacy of 3PC in enhancing intestinal residence time and eradicating H. pylori has been robustly substantiated in animal models, particularly in mice. In summary, 3PC is a formidable agent capable of eradicating H. pylori, irrespective of its antibiotic resistance status, by efficiently penetrating and selectively targeting the mucus layer within the gastric environment.
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Affiliation(s)
- Byoungjun Lim
- Department of BioMedical-Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea; Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea
| | - Kyoung Sub Kim
- Department of BioMedical-Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea; Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea
| | - Ji Yong Ahn
- Department of Gastroenterology, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea
| | - Kun Na
- Department of BioMedical-Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea; Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea.
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Sedarat Z, Taylor-Robinson AW. Helicobacter pylori Outer Membrane Proteins and Virulence Factors: Potential Targets for Novel Therapies and Vaccines. Pathogens 2024; 13:392. [PMID: 38787244 PMCID: PMC11124246 DOI: 10.3390/pathogens13050392] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 04/12/2024] [Accepted: 05/07/2024] [Indexed: 05/25/2024] Open
Abstract
Helicobacter pylori is a gastric oncopathogen that infects over half of the world's human population. It is a Gram-negative, microaerophilic, helix-shaped bacterium that is equipped with flagella, which provide high motility. Colonization of the stomach is asymptomatic in up to 90% of people but is a recognized risk factor for developing various gastric disorders such as gastric ulcers, gastric cancer and gastritis. Invasion of the human stomach occurs via numerous virulence factors such as CagA and VacA. Similarly, outer membrane proteins (OMPs) play an important role in H. pylori pathogenicity as a means to adapt to the epithelial environment and thereby facilitate infection. While some OMPs are porins, others are adhesins. The epithelial cell receptors SabA, BabA, AlpA, OipA, HopQ and HopZ have been extensively researched to evaluate their epidemiology, structure, role and genes. Moreover, numerous studies have been performed to seek to understand the complex relationship between these factors and gastric diseases. Associations exist between different H. pylori virulence factors, the co-expression of which appears to boost the pathogenicity of the bacterium. Improved knowledge of OMPs is a major step towards combatting this global disease. Here, we provide a current overview of different H. pylori OMPs and discuss their pathogenicity, epidemiology and correlation with various gastric diseases.
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Affiliation(s)
- Zahra Sedarat
- Cellular & Molecular Research Centre, Shahrekord University of Medical Sciences, Shahrekord 8813833435, Iran;
| | - Andrew W. Taylor-Robinson
- College of Health Sciences, VinUniversity, Gia Lam District, Hanoi 67000, Vietnam
- Center for Global Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 1904, USA
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Bhattacharjee A, Sahoo OS, Sarkar A, Bhattacharya S, Chowdhury R, Kar S, Mukherjee O. Infiltration to infection: key virulence players of Helicobacter pylori pathogenicity. Infection 2024; 52:345-384. [PMID: 38270780 DOI: 10.1007/s15010-023-02159-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 12/13/2023] [Indexed: 01/26/2024]
Abstract
PURPOSE This study aims to comprehensively review the multifaceted factors underlying the successful colonization and infection process of Helicobacter pylori (H. pylori), a prominent Gram-negative pathogen in humans. The focus is on elucidating the functions, mechanisms, genetic regulation, and potential cross-interactions of these elements. METHODS Employing a literature review approach, this study examines the intricate interactions between H. pylori and its host. It delves into virulence factors like VacA, CagA, DupA, Urease, along with phase variable genes, such as babA, babC, hopZ, etc., giving insights about the bacterial perspective of the infection The association of these factors with the infection has also been added in the form of statistical data via Funnel and Forest plots, citing the potential of the virulence and also adding an aspect of geographical biasness to the virulence factors. The biochemical characteristics and clinical relevance of these factors and their effects on host cells are individually examined, both comprehensively and statistically. RESULTS H. pylori is a Gram-negative, spiral bacterium that successfully colonises the stomach of more than half of the world's population, causing peptic ulcers, gastric cancer, MALT lymphoma, and other gastro-duodenal disorders. The clinical outcomes of H. pylori infection are influenced by a complex interplay between virulence factors and phase variable genes produced by the infecting strain and the host genetic background. A meta-analysis of the prevalence of all the major virulence factors has also been appended. CONCLUSION This study illuminates the diverse elements contributing to H. pylori's colonization and infection. The interplay between virulence factors, phase variable genes, and host genetics determines the outcome of the infection. Despite biochemical insights into many factors, their comprehensive regulation remains an understudied area. By offering a panoramic view of these factors and their functions, this study enhances understanding of the bacterium's perspective, i.e. H. pylori's journey from infiltration to successful establishment within the host's stomach.
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Affiliation(s)
- Arghyadeep Bhattacharjee
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India
- Department of Microbiology, Kingston College of Science, Beruanpukuria, Barasat, West Bengal, 700219, India
| | - Om Saswat Sahoo
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India
| | - Ahana Sarkar
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India
| | - Saurabh Bhattacharya
- Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, The Hebrew University of Jerusalem, P.O.B. 12272, 9112001, Jerusalem, Israel
| | - Rukhsana Chowdhury
- School of Biological Sciences, RKM Vivekananda Educational and Research Institute Narendrapur, Kolkata, India
| | - Samarjit Kar
- Department of Mathematics, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India
| | - Oindrilla Mukherjee
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India.
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Sian-Hülsmann J. Wilful pathogens provoke a gut feeling in Parkinson’s disease. J Neural Transm (Vienna) 2021; 129:557-562. [PMID: 34923593 PMCID: PMC8684782 DOI: 10.1007/s00702-021-02448-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 11/24/2021] [Indexed: 12/17/2022]
Abstract
Parkinson’s disease is the second most common neurological disorder marked by characteristic poverty and dysfunction in movement. There are many mechanisms and factors which have been postulated to be associated with the neurodegenerative pathway(s) resulting in distinctive loss of neurons in the substantia nigra. Subsequently, the neuropathology is more widespread and exhibited in other areas of the brain, and enteric nervous system. Aggregates of misfolded α-synuclein or Lewy bodies are the hallmark of the illness and appear to be central in the whole cascade of cell destruction. There are many processes implicated in neuronal destruction including: oxidative stress, excitotoxicity, mitochondrial dysfunction, an imbalance in protein homeostasis and neuroinflammation. Interesting, inflammation induced by pathogens (including, bacteria and viruses) has been associated in the pathogenesis of the disease. Bacteria such as Helicobacter pylori and Helicobacter suis appear to colonise the gut, and elicit systemic immune responses, which is them transmitted via the gut-axis to the brain, where cytotoxic cytokines induce neuroinflammation and cell death. This conforms to the bottom–top hypothesis proposed by Braak. The gut is also implicated in two other theories postulated in the development and progression of the disorder, namely, the top–down and the threshold. There is a possibility that these theories may be inter-linked and operate together to certain degree. Ultimately specific trigger factors or conditions may govern the occurrences of these processes in genetically predisposed individuals. Nevertheless, the importance of pathogen-related gut infections cannot be overlooked, since it can result in dysbiosis of gut microbes, which may orchestrate α-synuclein pathology and eventually cell destruction.
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Affiliation(s)
- Jeswinder Sian-Hülsmann
- Department of Medical Physiology, University of Nairobi, P.O. Box 30197, Nairobi, 00100, Kenya.
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Dos Santos MP, Pereira JN, De Labio RW, Carneiro LC, Pontes JC, Barbosa MS, Smith MDAC, Payão SLM, Rasmussen LT. Decrease of miR-125a-5p in Gastritis and Gastric Cancer and Its Possible Association with H. pylori. J Gastrointest Cancer 2021; 52:569-574. [PMID: 32504357 DOI: 10.1007/s12029-020-00432-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE The aim of this study was to evaluate the expression of miR-125a-5p in patients with dyspeptic symptoms and gastric cancer, correlating them with the development of this cancer and H. pylori. METHODS Patients were divided in groups according to histopathological analysis (control, gastritis, and cancer groups). Polymerase chain reaction was performed to detect H. pylori and real-time quantitative PCR to determine miR-125a-5p expression. RESULTS H. pylori was detected in 44% of the patients, with prevalence in the gastritis and cancer groups. A statistically significant decrease of miR-125a-5p expression was found in the control positive (p = 0.0183*), gastritis positive (p = 0.0380*), and cancer positive (p = 0.0288*) groups when compared with the control negative group. CONCLUSION We suggest that decreased expression of the miRNA-125a-5p associated with the presence of the H. pylori is an important mechanism in gastric diseases and could be a possible marker for early diagnosis of gastric cancer.
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Affiliation(s)
- Mônica Pezenatto Dos Santos
- Genetics Laboratory, Marília Medical School (FAMEMA), Lourival Freire, 240, Bairro Fragata, Marília, São Paulo, CEP 17519-050, Brazil
| | - Jéssica Nunes Pereira
- Genetics Laboratory, Marília Medical School (FAMEMA), Lourival Freire, 240, Bairro Fragata, Marília, São Paulo, CEP 17519-050, Brazil
| | - Roger Willian De Labio
- Genetics Laboratory, Marília Medical School (FAMEMA), Lourival Freire, 240, Bairro Fragata, Marília, São Paulo, CEP 17519-050, Brazil
| | - Lilian Carla Carneiro
- Institute of Tropical Pathology and Public Health, Federal University of Goiás (UFG), Goiânia, Goiás, Brazil
| | - Jaqueline Correia Pontes
- Institute of Tropical Pathology and Public Health, Federal University of Goiás (UFG), Goiânia, Goiás, Brazil
| | - Mônica Santiago Barbosa
- Institute of Tropical Pathology and Public Health, Federal University of Goiás (UFG), Goiânia, Goiás, Brazil
| | | | - Spencer Luíz Marques Payão
- Genetics Laboratory, Marília Medical School (FAMEMA), Lourival Freire, 240, Bairro Fragata, Marília, São Paulo, CEP 17519-050, Brazil
| | - Lucas Trevizani Rasmussen
- Biochemistry Department, Marília Medical School (FAMEMA), Lourival Freire, 240, Bairro Fragata, Marília, São Paulo, CEP 17519-050, Brazil.
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Isolation of dupA-positive and clarithromycin-resistant Helicobacter pylori from Iranian patients with duodenal ulcer. GENE REPORTS 2021. [DOI: 10.1016/j.genrep.2021.101228] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Karbalaei M, Hussein NR, Keikha M. Predicting the role of dupA-positive Helicobacter pylori strains in severe gastrointestinal disorders: An updated meta-analysis. GENE REPORTS 2021; 24:101263. [DOI: 10.1016/j.genrep.2021.101263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Cho K, Lee HG, Piao JY, Kim SJ, Na HK, Surh YJ. Protective Effects of Silibinin on Helicobacter pylori-induced Gastritis: NF-κB and STAT3 as Potential Targets. J Cancer Prev 2021; 26:118-127. [PMID: 34258250 PMCID: PMC8249208 DOI: 10.15430/jcp.2021.26.2.118] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 02/24/2021] [Accepted: 02/24/2021] [Indexed: 12/25/2022] Open
Abstract
More than half of the world's populations are considered to be infected by Helicobacter pylori. It causes a chronic inflammation of the stomach, which is implicated in the pathogenesis of gastric ulcer and cancer. Silibinin, a polyphenolic flavonoid derived from milk thistle, has been known for its hepatoprotective effects, and recent studies have revealed its chemopreventive potential. In the present study, we examined the anti-inflammatory effects of silibinin in human gastric cancer MKN-1 cells and in the stomach of C57BL/6 mice infected by H. pylori. Pretreatment with silibinin attenuated the up-regulation of COX-2 and inducible nitric oxide synthase (iNOS) in H. pylori-infected MKN-1 cells and mouse stomach. In addition, the elevated translocation and DNA binding of NF-κB and STAT3 induced by H. pylori infection were inhibited by silibinin treatment. Moreover, H. pylori infection in combination with high salt diet resulted in dysplasia and hyperplasia in mouse stomach, and these pathological manifestations were substantially mitigated by silibinin administration. Taken together, these findings suggest that silibinin exerts anti-inflammatory effects against H. pylori infection through suppression of NF-κB and STAT3 and subsequently, expression of COX-2 and iNOS.
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Affiliation(s)
- Kyunghwa Cho
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea
| | - Hee Geum Lee
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea
| | - Juan-Yu Piao
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea
| | - Su-Jung Kim
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea
| | - Hye-Kyung Na
- Department of Food Science and Biotechnology, College of Knowledge-based Services Engineering, Sungshin Women's University, Seoul, Korea
| | - Young-Joon Surh
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.,Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.,Cancer Research Institute, Seoul National University, Seoul, Korea
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Soyfoo DM, Doomah YH, Xu D, Zhang C, Sang HM, Liu YY, Zhang GX, Jiang JX, Xu SF. New genotypes of Helicobacter Pylori VacA d-region identified from global strains. BMC Mol Cell Biol 2021; 22:4. [PMID: 33413074 PMCID: PMC7791883 DOI: 10.1186/s12860-020-00338-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 12/16/2020] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Pathogenesis of Helicobacter Pylori (HP) vacuolating toxin A (vacA) depends on polymorphic diversity within the signal (s), middle (m), intermediate (i), deletion (d) and c-regions. These regions show distinct allelic diversity. The s-region, m-region and the c-region (a 15 bp deletion at the 3'-end region of the p55 domain of the vacA gene) exist as 2 types (s1, s2, m1, m2, c1 and c2), while the i-region has 3 allelic types (i1, i2 and i3). The locus of d-region of the vacA gene has also been classified into 2 genotypes, namely d1 and d2. We investigated the "d-region"/"loop region" through bioinformatics, to predict its properties and relation to disease. One thousand two hundred fifty-nine strains from the NCBI nucleotide database and the dryad database with complete vacA sequences were included in the study. The sequences were aligned using BioEdit and analyzed using Lasergene and BLAST. The secondary structure and physicochemical properties of the region were predicted using PredictProtein. RESULTS We identified 31 highly polymorphic genotypes in the "d-region", with a mean length of 34 amino acids (9 ~ 55 amino acids). We further classified the 31 genotypes into 3 main types, namely K-type (strains starting with the KDKP motif in the "d-region"), Q-type (strains starting with the KNQT motif), and E-type (strains starting with the ESKT motif) respectively. The most common type, K-type, is more prevalent in cancer patients (80.87%) and is associated with the s1i1m1c1 genotypes (P < .01). Incidentally, a new region expressing sequence diversity (2 aa deletion) at the C-terminus of the p55 domain of vacA was identified during bioinformatics analysis. CONCLUSIONS Prediction of secondary structures shows that the "d-region" adopts a loop conformation and is a disordered region.
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Affiliation(s)
- Djaleel Muhammad Soyfoo
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yussriya Hanaa Doomah
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Dong Xu
- Department of Electrical Engineering and Computer Science, Bond Life Sciences Center, University of Missouri, Columbia, MO, USA
| | - Chao Zhang
- Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, 10021, USA.,Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY, 10021, USA
| | - Huai-Ming Sang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yan-Yan Liu
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Guo-Xin Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jian-Xia Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
| | - Shun-Fu Xu
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
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Dos Santos Pereira E, Magalhães Albuquerque L, de Queiroz Balbino V, da Silva Junior WJ, Rodriguez Burbano RM, Pordeus Gomes JP, Barem Rabenhorst SH. Helicobacter pylori cagE, cagG, and cagM can be a prognostic marker for intestinal and diffuse gastric cancer. INFECTION GENETICS AND EVOLUTION 2020; 84:104477. [PMID: 32736040 DOI: 10.1016/j.meegid.2020.104477] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 07/21/2020] [Accepted: 07/23/2020] [Indexed: 01/15/2023]
Abstract
It is known that Helicobacter pylori is the main cause of peptic ulceration and gastric cancer. However, there is a lack of information on whether H. pylori strains may differ in gastric cancer histological subtypes. This study aimed to investigate different H. pylori strains considering six cag Pathogenicity Island - cagPAI genes (cagA, cagE, cagG, cagM, cagT, and virb11), and vacuolating cytotoxin - vacA alleles, and their relation to gastric cancer histologic subtypes. For this purpose, tumor samples from 285 patients with gastric carcinoma were used. H. pylori infection and genotypes were determined by polymerase chain reaction (PCR). H. pylori was detected in 93.9% of gastric tumors. For comparative analyzes between histopathological subtypes considering H. pylori cagPAI genes the strains were grouped according to the vacA s1/s2 alleles. In the vacAs1 group, the strains cagA(-)cagE(+), cagA(+)cagE(+)cagG(+), cagA(+)cagM(+), or only cagE(+) strains were more frequent in the intestinal subtype (P = .009; P = .024; P = .046, respectively). In contrast, cagM(+)cagG(+)cagA(-) and cagE(-) were associated with diffuse tumors (P = .036), highlighting the presence of cagE in the development of intestinal tumors, and the presence of cagG and absence of cagE in diffuse tumors. Furthermore, WEKA software and Decision Tree (CART) analyses confirmed these findings, in which cagE presence was associated with intestinal tumors, and cagE absence and cagG(+) with diffuse tumors. In conclusion our results showed that vacAs1 (cagG + cagM) strains, mainly cagG positive with cagE absence, were relevant in the studied population for the diffuse outcome, while the presence of cagE was relevant for the intestinal outcome. These findings suggest the relevance of these H. pylori genes as potential markers for gastric cancer histological outcomes.
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Affiliation(s)
- Eliane Dos Santos Pereira
- Department of Pathology and Forensic Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | | | - Valdir de Queiroz Balbino
- Department of Genetics, Biomedical Center, Federal University of Pernambuco, Recife, Pernambuco, Brazil
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Fischer W, Tegtmeyer N, Stingl K, Backert S. Four Chromosomal Type IV Secretion Systems in Helicobacter pylori: Composition, Structure and Function. Front Microbiol 2020; 11:1592. [PMID: 32754140 PMCID: PMC7366825 DOI: 10.3389/fmicb.2020.01592] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 06/18/2020] [Indexed: 12/14/2022] Open
Abstract
The pathogenic bacterium Helicobacter pylori is genetically highly diverse and a major risk factor for the development of peptic ulcer disease and gastric adenocarcinoma in humans. During evolution, H. pylori has acquired multiple type IV secretion systems (T4SSs), and then adapted for various purposes. These T4SSs represent remarkable molecular transporter machines, often associated with an extracellular pilus structure present in many bacteria, which are commonly composed of multiple structural proteins spanning the inner and outer membranes. By definition, these T4SSs exhibit central functions mediated through the contact-dependent conjugative transfer of mobile DNA elements, the contact-independent release and uptake of DNA into and from the extracellular environment as well as the secretion of effector proteins in mammalian host target cells. In recent years, numerous features on the molecular functionality of these T4SSs were disclosed. H. pylori encodes up to four T4SSs on its chromosome, namely the Cag T4SS present in the cag pathogenicity island (cagPAI), the ComB system, as well as the Tfs3 and Tfs4 T4SSs, some of which exhibit unique T4SS functions. The Cag T4SS facilitates the delivery of the CagA effector protein and pro-inflammatory signal transduction through translocated ADP-heptose and chromosomal DNA, while various structural pilus proteins can target host cell receptors such as integrins or TLR5. The ComB apparatus mediates the import of free DNA from the extracellular milieu, whereas Tfs3 may accomplish the secretion or translocation of effector protein CtkA. Both Tfs3 and Tfs4 are furthermore presumed to act as conjugative DNA transfer machineries due to the presence of tyrosine recombinases with cognate recognition sequences, conjugational relaxases, and potential origins of transfer (oriT) found within the tfs3 and tfs4 genome islands. In addition, some extrachromosomal plasmids, transposons and phages have been discovered in multiple H. pylori isolates. The genetic exchange mediated by DNA mobilization events of chromosomal genes and plasmids combined with recombination events could account for much of the genetic diversity found in H. pylori. In this review, we highlight our current knowledge on the four T4SSs and the involved mechanisms with consequences for H. pylori adaptation to the hostile environment in the human stomach.
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Affiliation(s)
- Wolfgang Fischer
- Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Medizinische Fakultät, LMU München, Munich, Germany
| | - Nicole Tegtmeyer
- Department Biologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Kerstin Stingl
- Department of Biological Safety, National Reference Laboratory for Campylobacter, German Federal Institute for Risk Assessment (BfR), Berlin, Germany
| | - Steffen Backert
- Department Biologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
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14
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Kondekar SM, Gunjal GV, Pablo Radicella J, Rao DN. Molecular dissection of Helicobacter pylori Topoisomerase I reveals an additional active site in the carboxyl terminus of the enzyme. DNA Repair (Amst) 2020; 91-92:102853. [PMID: 32447233 DOI: 10.1016/j.dnarep.2020.102853] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 03/07/2020] [Accepted: 04/05/2020] [Indexed: 12/15/2022]
Abstract
DNA topoisomerases play a crucial role in maintaining DNA superhelicity, thereby regulating various cellular processes. Unlike most other species, the human pathogen Helicobacter pylori has only two topoisomerases, Topoisomerase I and DNA gyrase, the physiological roles of which remain to be explored. Interestingly, there is enormous variability among the C-terminal domains (CTDs) of Topoisomerase I across bacteria. H. pylori Topoisomerase I (HpTopoI) CTD harbors four zinc finger motifs (ZFs). We show here that sequential deletion of the third and/or fourth ZFs had only a marginal effect on the HpTopoI activity, while deletion of the second, third and fourth ZFs severely reduced DNA relaxation activity. Deletion of all ZFs drastically hampered DNA binding and thus abolished DNA relaxation. Surprisingly, mutagenesis of the annotated active site tyrosine residue (Y297 F) did not abrogate the enzyme activity and HpTopoI CTD alone (spanning the four ZFs) showed DNA relaxation activity. Additionally, a covalent linkage between the DNA and HpTopoI CTD was identified. The capacity of HpTopoI CTD to complement Escherichia coli topA mutant strains further supported the in vitro observations. Collectively these results imply that not all ZFs are dispensable for HpTopoI activity and unveil the presence of additional non-canonical catalytic site(s) within the enzyme.
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Affiliation(s)
- Sumedha M Kondekar
- Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India
| | - Gaurav V Gunjal
- Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India
| | - Juan Pablo Radicella
- Institute of Cellular and Molecular Radiobiology, Institut de Biologie François Jacob, CEA, F-92265 Fontenay aux Roses, France; Université de Paris and Université Paris-Saclay, F-92265 Fontenay aux Roses, France
| | - Desirazu N Rao
- Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
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15
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Sun DL, Gong ZH, Shao SL, Shi XL, Yuan XY, Luo H, Wang MY. virB11 gene potentially involves in ATP metabolism to provide energy in H. pylori infection. Microb Pathog 2020; 142:104067. [PMID: 32061915 DOI: 10.1016/j.micpath.2020.104067] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Revised: 02/12/2020] [Accepted: 02/12/2020] [Indexed: 02/07/2023]
Abstract
Helicobater pylori (H. pylori) is the most important bacteria known to be associated with various gastroduodenal diseases. virB11 gene is a structural gene of tfs3a genes cluster in the plasticity region of H. pylori. In this study, the structure and biology of virB11 gene were analyzed and elucidated with bioinformatics analysis. After cloning, expression and purification, VirB11 protein was generated for the cytotoxicity to GES-1 cells and the anti-VirB11 protein antibody production for localization and interaction proteins analysis. The results showed that VirB11 protein is a hydrophilic protein, mainly locates in cell membrane. IL-8 productions from GES-1 cells co-culture with VirB11 protein were increased gradually with time (p < 0.001). The interaction proteins of VirB11 protein were F0F1 ATP synthase subunit alpha, ATP synthase subunit beta and isocitrate dehydrogenase. We demonstrate that VirB11 protein possesses cytotoxicity and potentially plays important roles in ATP metabolism to provide energy in the course of H. pylori infection.
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Affiliation(s)
- Da-Lin Sun
- Department of Central Lab, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, Shandong, 264200, PR China; School of Laboratory Medicine, Dalian Medical University, Dalian, Liaoning, 116044, PR China
| | - Zhen-Hua Gong
- Department of Genetics Lab, Zibo Maternal and Child Health Hospital, Zibo, Shandong, 255000, PR China
| | - Shu-Li Shao
- Department of Central Lab, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, Shandong, 264200, PR China
| | - Xiao-Lin Shi
- School of Laboratory Medicine, Dalian Medical University, Dalian, Liaoning, 116044, PR China
| | - Xiao-Yan Yuan
- Department of Central Lab, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, Shandong, 264200, PR China
| | - Hong Luo
- School of Laboratory Medicine, Dalian Medical University, Dalian, Liaoning, 116044, PR China.
| | - Ming-Yi Wang
- Department of Central Lab, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, Shandong, 264200, PR China.
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16
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Smith SI, Jolaiya T, Fowora M, Ugiagbe R, Onyekwere C, Agbo I, Lesi O, Palamides P, Adedeji A, Ndububa D, Adekanle O, Adeleye I, Bamidele M, Ngoka F, Ayodeji I, Njom H, Pellicano R. Comparison of polymerase chain reaction-based genotyping of Helicobacter pylori by direct polymerase chain reaction from biopsies and cultures from patients with dyspepsia in Nigeria. MINERVA BIOTECNOL 2019; 31. [DOI: 10.23736/s1120-4826.19.02558-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
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17
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de Brito BB, da Silva FAF, Soares AS, Pereira VA, Santos MLC, Sampaio MM, Neves PHM, de Melo FF. Pathogenesis and clinical management of Helicobacter pylori gastric infection. World J Gastroenterol 2019; 25:5578-5589. [PMID: 31602159 PMCID: PMC6785516 DOI: 10.3748/wjg.v25.i37.5578] [Citation(s) in RCA: 165] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Revised: 08/14/2019] [Accepted: 08/19/2019] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a gram-negative bacterium that infects approximately 4.4 billion individuals worldwide. However, its prevalence varies among different geographic areas, and is influenced by several factors. The infection can be acquired by means of oral-oral or fecal-oral transmission, and the pathogen possesses various mechanisms that improve its capacity of mobility, adherence and manipulation of the gastric microenvironment, making possible the colonization of an organ with a highly acidic lumen. In addition, H. pylori presents a large variety of virulence factors that improve its pathogenicity, of which we highlight cytotoxin associated antigen A, vacuolating cytotoxin, duodenal ulcer promoting gene A protein, outer inflammatory protein and gamma-glutamyl transpeptidase. The host immune system, mainly by means of a Th1-polarized response, also plays a crucial role in the infection course. Although most H. pylori-positive individuals remain asymptomatic, the infection predisposes the development of various clinical conditions as peptic ulcers, gastric adenocarcinomas and mucosa-associated lymphoid tissue lymphomas. Invasive and non-invasive diagnostic methods, each of them with their related advantages and limitations, have been applied in H. pylori detection. Moreover, bacterial resistance to antimicrobial therapy is a major challenge in the treatment of this infection, and new therapy alternatives are being tested to improve H. pylori eradication. Last but not least, the development of effective vaccines against H. pylori infection have been the aim of several research studies.
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Affiliation(s)
- Breno Bittencourt de Brito
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | | | - Aline Silva Soares
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Vinícius Afonso Pereira
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Maria Luísa Cordeiro Santos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Mariana Miranda Sampaio
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Pedro Henrique Moreira Neves
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
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18
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Zaraatgar Gohardani HR, Moghanloo E, Badameh P, Rezaei S, Babaei V, Teimourian S. The Significant Association of the dupA and cagA genes of Helicobacter pylori with Peptic Ulcer. ACTA ACUST UNITED AC 2018. [DOI: 10.29252/jhehp.4.4.3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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19
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Waskito LA, Yih-Wu J, Yamaoka Y. The role of integrating conjugative elements in Helicobacter pylori: a review. J Biomed Sci 2018; 25:86. [PMID: 30497458 PMCID: PMC6264033 DOI: 10.1186/s12929-018-0489-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Accepted: 11/16/2018] [Indexed: 12/15/2022] Open
Abstract
The genome of Helicobacter pylori contains many putative genes, including a genetic region known as the Integrating Conjugative Elements of H. pylori type four secretion system (ICEHptfs). This genetic regions were originally termed as "plasticity zones/regions" due to the great genetic diversity between the original two H. pylori whole genome sequences. Upon analysis of additional genome sequences, the regions were reported to be extremely common within the genome of H. pylori. Moreover, these regions were also considered conserved rather than genetically plastic and were believed to act as mobile genetic elements transferred via conjugation. Although ICEHptfs(s) are highly conserved, these regions display great allele diversity, especially on ICEHptfs4, with three different subtypes: ICEHptfs4a, 4b, and 4c. ICEHptfs were also reported to contain a novel type 4 secretion system (T4SS) with both epidemiological and in vitro infection model studies highlighting that this novel T4SS functions primarily as a virulence factor. However, there is currently no information regarding the structure, the genes responsible for forming the T4SS, and the interaction between this T4SS and other virulence genes. Unlike the cag pathogenicity island (PAI), which contains CagA, a gene found to be essential for H. pylori virulence, these novel T4SSs have not yet been reported to contain genes that contribute significant effects to the entire system. This notion prompted the hypothesis that these novel T4SSs may have different mechanisms involving cag PAI.
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Affiliation(s)
- Langgeng Agung Waskito
- Department of Environmental and Preventive Medicine, Oita University, Faculty of Medicine, Yufu City, Oita, Japan.,Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
| | - Jeng Yih-Wu
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University, Faculty of Medicine, Yufu City, Oita, Japan. .,Department of Medicine, Gastroenterology Section, Baylor College of Medicine, Houston, TX, USA. .,Global Oita Medical Advanced Research Center for Health, Yufu City, Oita, Japan.
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20
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de Brito BB, da Silva FAF, de Melo FF. Role of polymorphisms in genes that encode cytokines and Helicobacter pylori virulence factors in gastric carcinogenesis. World J Clin Oncol 2018; 9:83-89. [PMID: 30254963 PMCID: PMC6153128 DOI: 10.5306/wjco.v9.i5.83] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Revised: 06/23/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
The Helicobacter pylori (H. pylori) infection is a determinant factor in gastric cancer (GC) development. However, the infection outcomes are variable and depend on both host and bacterial characteristics. Some host cytokines such as interleukin (IL)-1β, IL-1Ra, IL-8, IL-10 and tumor necrosis factor-α play important roles in the host immune system response to the pathogen, in the development of gastric mucosal lesions and in cell malignant transformation. Therefore, these host factors are crucial in neoplastic processes. Certain polymorphisms in genes that encode these cytokines have been associated with an increased risk of GC. On the other hand, various virulence factors found in distinct H. pylori bacterial strains, including cytotoxin-associated antigen A, vacuolating cytotoxin, duodenal ulcer promoting gene A protein, outer inflammatory protein and blood group antigen binding adhesin, have been associated with the pathogenesis of different gastric diseases. The virulent factors mentioned above allow the successful infection by the bacterium and play crucial roles in gastric mucosa lesions, including malignant transformation. Moreover, the role of host polymorphisms and bacterial virulence factors in gastric carcinogenesis seems to vary among different countries and populations. The identification of host and bacterium factors that are associated with an increased risk of GC development may be useful in determining the prognosis of infection in patients, what could help in clinical decision-making and in providing of an optimized clinical approach.
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Affiliation(s)
- Breno Bittencourt de Brito
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Brazil
| | | | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Brazil
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21
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Yuan XY, Wang Y, Wang MY. The type IV secretion system in Helicobacter pylori. Future Microbiol 2018; 13:1041-1054. [PMID: 29927340 DOI: 10.2217/fmb-2018-0038] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Helicobacter pylori (H. pylori) has an essential role in the pathogenesis of gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma and gastric cancer. The severity of the host inflammatory responses against the bacteria have been straightly associated with a special bacterial virulence factor, the cag pathogenicity island, which is a type IV secretion system (T4SS) to deliver CagA into the host cells. Besides cag-T4SS, the chromosomes of H. pylori can encode another three T4SSs, including comB, tfs3 and tfs4. In this review, we systematically reviewed the four T4SSs of H. pylori and explored their roles in the pathogenesis of gastroduodenal diseases. The information summarized in this review might provide valuable insights into the pathogenic mechanism for H. pylori.
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Affiliation(s)
- Xiao-Yan Yuan
- Department of Central Lab, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, Shandong, 264200, PR China
| | - Ying Wang
- Department of Central Lab, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, Shandong, 264200, PR China
| | - Ming-Yi Wang
- Department of Central Lab, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, Shandong, 264200, PR China
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22
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Waskito LA, Miftahussurur M, Lusida MI, Syam AF, Suzuki R, Subsomwong P, Uchida T, Hamdan M, Nasronudin, Yamaoka Y. Distribution and clinical associations of integrating conjugative elements and cag pathogenicity islands of Helicobacter pylori in Indonesia. Sci Rep 2018; 8:6073. [PMID: 29666390 PMCID: PMC5904169 DOI: 10.1038/s41598-018-24406-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Accepted: 03/26/2018] [Indexed: 12/11/2022] Open
Abstract
The clinical associations and correlations with other virulence factors such as cag pathogenicity island (PAI) of the Integrating Conjugative Elements Helicobacter pylori TFSS (ICEHptfs), a new type IV secretion system (TFSS) in H. pylori has not been described. Among 103 studied strains from Indonesia, almost all strains (99.0%) contained cag PAI with more than half (55.8%) were intact cag PAI. Patients infected with intact cag PAI strains showed significantly higher antral activity, inflammation and atrophy as well as corporal inflammation than those with non-intact cag PAI strains, confirming the virulence of cag PAI. Over half of strains (53.8%) contained ICEHptfs, predominantly consisted of ICEHptfs3-tfs4a (42.8%) and ICEHptfs3 (16.3%). Although patients infected with ICEHptfs-positive strains had lower H. pylori density, those with the complete ICEHptfs4b strains tended to have higher antral activity than the negative one. In combination, patients infected with combination of intact cag PAI-ICEHptfs-positive strains had more severe inflammation than those with non-intact cag PAI-ICEHptfs-negative, suggesting a possibility of a mutual correlation between these TFSS(s).
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Affiliation(s)
- Langgeng Agung Waskito
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan.,Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
| | - Muhammad Miftahussurur
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan.,Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.,Gastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Maria Inge Lusida
- Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
| | - Ari Fahrial Syam
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Rumiko Suzuki
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
| | - Phawinee Subsomwong
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
| | - Tomohisa Uchida
- Department of Molecular Pathology, Oita University Faculty of Medicine, Yufu, Japan
| | - Muhammad Hamdan
- Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.,Faculty of Medicine, Universitas Muhammadiyah Surabaya, Surabaya, Indonesia
| | - Nasronudin
- Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan. .,Department of Medicine, Gastroenterology and Hepatology section, Baylor College of Medicine, Houston, Texas, USA.
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23
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Zabaglia LM, Sallas ML, Santos MPD, Orcini WA, Peruquetti RL, Constantino DH, Chen E, Smith MDAC, Payão SM, Rasmussen LT. Expression of miRNA‐146a, miRNA‐155, IL‐2, and TNF‐α in inflammatory response to
Helicobacter pylori
infection associated with cancer progression. Ann Hum Genet 2017; 82:135-142. [DOI: 10.1111/ahg.12234] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 10/19/2017] [Accepted: 11/10/2017] [Indexed: 02/06/2023]
Affiliation(s)
| | | | | | | | | | | | - Elizabeth Chen
- Universidade Federal de São Paulo (UNIFESP) São Paulo São Paulo Brazil
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24
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Ji X, Wang Y, Li J, Rong Q, Chen X, Zhang Y, Liu X, Li B, Zhao H. Application of FLP-FRT System to Construct Unmarked Deletion in Helicobacter pylori and Functional Study of Gene hp0788 in Pathogenesis. Front Microbiol 2017; 8:2357. [PMID: 29238332 PMCID: PMC5712585 DOI: 10.3389/fmicb.2017.02357] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Accepted: 11/15/2017] [Indexed: 12/21/2022] Open
Abstract
Helicobacter pylori is a Gram-negative, microaerophilic bacterium associated with human gastric diseases. Further investigations on virulence genes are still required to clarify the pathogenic mechanism of H. pylori and the heterogeneous problem of infection. In order to develop an efficient and accurate method to study gene functions in H. pylori pathogenesis, an unmarked deletion method for both a single gene and a large fragment was established based on the FLP-FRT recombination system. Using this method, the gene hp0788, encoding an outer membrane protein (HofF), was deleted. Deletion of hp0788 did not affect growth or motility of H. pylori, but reduced the adherence of the bacteria to gastric epithelial cells. The apoptosis of GES-1 cells caused by H. pylori infection was also reduced by the defection of hp0788. These suggest that hp0788 takes part in the bacterium-host interaction and plays an important role in H. pylori infection. Furthermore, a large genomic fragment deletion from hp0541 to hp0547 in cag pathogenicity island was also successfully achieved using FLP-FRT method. The innovative application of the FLP-FRT recombination system in H. pylori to construct unmarked deletion would provide a helpful tool for further function research of putative pathogenic genes and contribute to the understanding of H. pylori pathogenesis.
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Affiliation(s)
- Xiaofei Ji
- Department of Pathogenic Biology, School of Basic Medical Sciences, Binzhou Medical University, Yantai, China
| | - Ying Wang
- Central Laboratory, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China
| | - Jiaojiao Li
- Department of Pathogenic Biology, School of Basic Medical Sciences, Binzhou Medical University, Yantai, China
| | - Qianyu Rong
- Department of Pathogenic Biology, School of Basic Medical Sciences, Binzhou Medical University, Yantai, China
| | - Xingxing Chen
- Department of Pathogenic Biology, School of Basic Medical Sciences, Binzhou Medical University, Yantai, China
| | - Ying Zhang
- Department of Pathogenic Biology, School of Basic Medical Sciences, Binzhou Medical University, Yantai, China
| | - Xiaoning Liu
- Central Laboratory, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China
| | - Boqing Li
- Department of Pathogenic Biology, School of Basic Medical Sciences, Binzhou Medical University, Yantai, China
| | - Huilin Zhao
- Department of Pathogenic Biology, School of Basic Medical Sciences, Binzhou Medical University, Yantai, China
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25
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Fatahi G, Tarbiat Modares University, Dept of Bacteriology, P.O. Box: 14115-111, Tehran, Iran, Talebi Bezmin Abadi A, Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.. A report on Allelic Variation in Helicobacter pylori dupA: A viewpoint. RESEARCH IN MOLECULAR MEDICINE 2017. [DOI: 10.29252/rmm.5.3.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
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26
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Jalilian S, Alvandi A, Jouybari TA, Pajavand H, Abiri R. Lack of association association between the presence of dupA and babA 2 genes in Helicobacter pylori and gastroduodenal disorders. MOLECULAR GENETICS MICROBIOLOGY AND VIROLOGY 2017. [DOI: 10.3103/s0891416817010074] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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27
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Effects of Different Environmental Factors and Virulence Factors, dupA and iceA Genes, of Helicobacter pylori on Peptic Ulcer. Jundishapur J Microbiol 2017. [DOI: 10.5812/jjm.40161] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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28
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De Re V, Repetto O, Zanussi S, Casarotto M, Caggiari L, Canzonieri V, Cannizzaro R. Protein signature characterizing Helicobacter pylori strains of patients with autoimmune atrophic gastritis, duodenal ulcer and gastric cancer. Infect Agent Cancer 2017; 12:22. [PMID: 28465717 PMCID: PMC5408474 DOI: 10.1186/s13027-017-0133-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Accepted: 04/13/2017] [Indexed: 12/12/2022] Open
Abstract
Background Helicobacter pylori (H. pylori) represents a key factor in the etiology of autoimmune atrophic gastritis (AAG), duodenal ulcer (DU) and gastric cancer (GC). The aim of this study was to characterize the differential protein expression of H. pylori isolated from gastric biopsies of patients affected by either AAG, DU or GC. Methods The H. pylori strains were isolated from endoscopic biopsies from the stomach of patients with gastric disease. Protein profiles of H. pylori were compared by two-dimensional difference in gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS) for the identification of significantly different spots (Student t-test, p < 0.05). Results A total of 47 differentially expressed spots were found between H. pylori isolated from patients with either DU or AAG diseases and those isolated from patients with GC (Anova < 0.05, log fold change >1.5). These spots corresponded to 35 unique proteins. The identity of 7 protein spots was validated after one-dimensional electrophoresis and MS/MS analyses of excised gel portions. In H. pylori isolated from DU-patients a significant increase in proteins with antioxidant activity emerged (AroQ, AspA, FldA, Icd, OorA and ScoB), together with a higher content of proteins counteracting the high acid environment (KatA and NapA). In H. pylori isolated from AAG-patients proteins neutralizing hydrogen concentrations through organic substance metabolic processes decreased (GroL, TrxB and Tuf). In addition, a reduction of bacterial motility (FlhA) was found to be associated with AAG-H. pylori isolates. In GC-H. pylori strains it was found an increase in nucleic acid-binding proteins (e.g. DnaG, Tuf, RpoA, RplU) which may be involved in a higher demand of DNA- and protein-related processes. Conclusion Our data suggest the presence of specific protein signatures discriminating among H. pylori isolated from either AAG, DU or GC. Changes in protein expression profiles evaluated by DIGE succeeded in deciphering part of the molecular scenarios associated with the different H. pylori-related gastric diseases. Electronic supplementary material The online version of this article (doi:10.1186/s13027-017-0133-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Valli De Re
- Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, IRCCS CRO National Cancer Institute, Via F. Gallini 2, 33081 Aviano, Italy
| | - Ombretta Repetto
- Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, IRCCS CRO National Cancer Institute, Via F. Gallini 2, 33081 Aviano, Italy
| | - Stefania Zanussi
- Microbiology-Immunology and Virology, IRCCS CRO National Cancer Institute, Aviano, Italy
| | - Mariateresa Casarotto
- Microbiology-Immunology and Virology, IRCCS CRO National Cancer Institute, Aviano, Italy
| | - Laura Caggiari
- Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, IRCCS CRO National Cancer Institute, Via F. Gallini 2, 33081 Aviano, Italy
| | - Vincenzo Canzonieri
- Pathology Gastroenterology, IRCCS CRO National Cancer Institute, Aviano, Italy
| | - Renato Cannizzaro
- Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, IRCCS CRO National Cancer Institute, Via F. Gallini 2, 33081 Aviano, Italy.,Microbiology-Immunology and Virology, IRCCS CRO National Cancer Institute, Aviano, Italy.,Pathology Gastroenterology, IRCCS CRO National Cancer Institute, Aviano, Italy.,Gastroenterology, IRCCS CRO National Cancer Institute, Aviano, Italy
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Polymorphisms and haplotypes of the interleukin 2 gene are associated with an increased risk of gastric cancer. The possible involvement of Helicobacter pylori. Cytokine 2017; 96:203-207. [PMID: 28458166 DOI: 10.1016/j.cyto.2017.04.020] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2016] [Revised: 04/19/2017] [Accepted: 04/20/2017] [Indexed: 12/11/2022]
Abstract
Interleukin 2 (IL-2) is a pro-inflammatory cytokine that is mainly synthesized by immunoregulatory T helper cells and which plays an important role in antitumor immunity. Helicobacter pylori (H. pylori) is a gram-negative bacterium that colonizes the gastric mucosa and induces the production of IL-2. This process increases the magnitude of inflammation and may influence the development of gastric pathologies. In light of the possible involvement of IL-2 and the presence of H. pylori in gastric diseases, this study investigated possible associations between the IL-2 polymorphisms +114 T>G (rs2069763) and -330 T>G (rs2069762) and the development of gastric cancer; these associations were then correlated with the presence of H. pylori. Gastric biopsies were obtained from 294 dyspeptic patients (173♀/123♂). Of these samples, 181 were chronic gastritis samples (102♀/79), 62 were samples of intact gastric mucosa (47♀/15♂), and 51 were samples of gastric cancer (22♀/29♂). PCR-RFLP was used to characterize the +114 T>G and -330 T>G polymorphisms. Considering the genetic characteristics of the study population and based on the codominant model, a high risk of gastric cancer among patients with normal gastric tissue and patients with gastric cancer was found in subjects with the IL-2-330 GG genotype (OR=6.43, 95% CI: 1.47-28.10, p=0.044). The data was adjusted for the presence of H. pylori. Among patients with gastritis and patients with gastric cancer, a high risk was found among subjects with the IL-2-330 GG genotype (OR=4.47, 95% CI: 1.84-10.84, p=0.0022). When the IL-2 +114 polymorphism was analyzed, similar results were found. Among the patients with normal gastric tissue and the patients with gastric cancer, subjects carrying the +114 TT genotype were found to be at a high risk of gastric cancer (OR=5.97, 95% CI: 1.60-22.27, p=0.013). This data was also adjusted for the presence of H. pylori. Among patients with gastritis and patients with gastric cancer, a high risk was found in subjects carrying the +114 TT genotype (OR=6.36, 95% CI: 2.66-15.21, p<0.0001). The haplotype was also analyzed. The -330G/+114T haplotype was found to be significantly associated with gastric cancer. Therefore, our results show that, among patients with H. pylori infection, the -330 GG and +114 TT genotypes are significantly associated with a high risk of developing gastric cancer, as is the -330G/+114T haplotype.
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Abstract
BACKGROUND Standard graphical tools for whole genome comparison require a reference genome. However, any reference is also subject to annotation biases and rearrangements, and may not serve as the standard except for those of extensively studied model species. To fully exploit the rapidly accumulating sequence data from the recent sequencing technologies, genome comparison without any reference has been anticipated. RESULTS We introduce a circular genome visualizer to compare complete genomes of closely related species. This tool visualizes the position of orthologous gene clusters rather than actual sequences or their features, thereby achieving the comparative view without using a single reference genome. The essential information is the matrix of orthologous gene clusters whose positions (not sequences) are color-coded in circular graphics. As a demonstration, comparison of 14 Lactobacillus paracasei strains and one L. casei strain revealed not only large-scale rearrangements but also genomic islands that are strain-specific. Comparison of 73 Helicobacter pylori strains confirmed their genetic consistency and also revealed the three general patterns of large-scale genome inversions. CONCLUSIONS From the ample sequence information in the GenBank/ENA/DDBJ repository, we can reconstruct a genomic consensus for particular species. By visualizing multiple strains at a glance, we can identify conserved as well as strain-specific regions in multiply sequenced genomes. Positional consistency for orthologous genes provides information orthogonal to major sequence features such as the GC content or sequence similarity of marker genes. The positional comparison is therefore useful for identifying large-scale genome rearrangements or gene transfers.
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Affiliation(s)
- Ipputa Tada
- Center for Information Biology, National Institute of Genetics, Mishima, Shizuoka 411-8540 Japan
- Department of Genetics, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Mishima, Shizuoka 411-8540 Japan
| | - Yasuhiro Tanizawa
- Center for Information Biology, National Institute of Genetics, Mishima, Shizuoka 411-8540 Japan
| | - Masanori Arita
- Center for Information Biology, National Institute of Genetics, Mishima, Shizuoka 411-8540 Japan
- RIKEN Center for Sustainable Resource Science, Yokohama, 230-0045 Japan
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Ji X, Zhao H, Zhang Y, Chen X, Li J, Li B. Construction of Novel Plasmid Vectors for Gene Knockout in Helicobacter pylori. Curr Microbiol 2016; 73:897-903. [DOI: 10.1007/s00284-016-1140-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Accepted: 09/13/2016] [Indexed: 02/07/2023]
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Ganguly M, Sarkar S, Ghosh P, Sarkar A, Alam J, Karmakar BC, De R, Saha DR, Mukhopadhyay AK. Helicobacter pylori plasticity region genes are associated with the gastroduodenal diseases manifestation in India. Gut Pathog 2016; 8:10. [PMID: 27006705 PMCID: PMC4802902 DOI: 10.1186/s13099-016-0093-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2015] [Accepted: 03/02/2016] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Almost all Helicobacter pylori infected person develop gastritis and severe gastritis is supposed to be the denominator of peptic ulcer diseases, which may lead to gastric cancer. However, it is still an enigma why few strains are associated with ulcer formation, while others are not related with any disease outcome. Although a number of putative virulence factors have been reported for H. pylori, there are contradictory results regarding their connotation with diseases. Recently, there has been a significant attention in strain-specific genes outside the cag pathogenicity island, especially genes within plasticity regions. Studies demonstrated that certain genes in this region may play important roles in the pathogenesis of H. pylori-associated diseases. The aim of this study was to assess the role of selected genes (jhp0940, jhp0945, jhp0947 and jhp0949) in the plasticity region in relation to risk of H. pylori-related diseases in Indian population. METHODS A total of 113 H. pylori strains isolated from duodenal ulcer (DU) (n = 61) and non-ulcer dyspepsia (NUD) subjects (n = 52) were screened by PCR and Dot-Blot to determine the presence of these genes. The comparative study of IL-8 production and apoptosis were also done by co-culturing the AGS cells with H. pylori strains of different genotype. RESULTS PCR and Dot-Blot results indicated that the prevalence rates of jhp0940, jhp0945, jhp0947 and jhp0949 in the H. pylori strains were 9.8, 47.5, 50.8, 40.9 % and 17.3, 28.8, 26.9, 19.2 % isolated from DU and NUD, respectively. IL-8 production and apoptotic cell death were significantly higher in H. pylori strains containing jhp0945, jhp0947 and jhp0949 than the strains lacking those genes. Results indicated that the prevalence of jhp0945, jhp0947 and jhp0949 are associated with increased risk of severe diseases in India. CONCLUSION Our study showed that presence of jhp0945, jhp0947 and jhp0949 were significantly associated with symptomatic expressions along with the increased virulence during in vitro study whereas jhp0940 seems to be negatively associated with the disease. These results suggest that jhp0945, jhp0947 and jhp0949 could be useful prognostic markers for the development of duodenal ulcer in India.
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Affiliation(s)
- Mou Ganguly
- Division of Bacteriology, National Institute of Cholera and Enteric Diseases, P 33, CIT Road, Scheme XM, Beliaghata, Kolkata, 700010 India ; Department of Zoology, University of Calcutta, Kolkata, India
| | | | - Prachetash Ghosh
- Division of Bacteriology, National Institute of Cholera and Enteric Diseases, P 33, CIT Road, Scheme XM, Beliaghata, Kolkata, 700010 India
| | - Avijit Sarkar
- Division of Bacteriology, National Institute of Cholera and Enteric Diseases, P 33, CIT Road, Scheme XM, Beliaghata, Kolkata, 700010 India
| | - Jawed Alam
- Division of Bacteriology, National Institute of Cholera and Enteric Diseases, P 33, CIT Road, Scheme XM, Beliaghata, Kolkata, 700010 India
| | - Bipul Chandra Karmakar
- Division of Bacteriology, National Institute of Cholera and Enteric Diseases, P 33, CIT Road, Scheme XM, Beliaghata, Kolkata, 700010 India
| | - Ronita De
- Division of Bacteriology, National Institute of Cholera and Enteric Diseases, P 33, CIT Road, Scheme XM, Beliaghata, Kolkata, 700010 India
| | - Dhira Rani Saha
- Division of Bacteriology, National Institute of Cholera and Enteric Diseases, P 33, CIT Road, Scheme XM, Beliaghata, Kolkata, 700010 India
| | - Asish K Mukhopadhyay
- Division of Bacteriology, National Institute of Cholera and Enteric Diseases, P 33, CIT Road, Scheme XM, Beliaghata, Kolkata, 700010 India
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Wang MY, Liu XF, Gao XZ. Helicobacter pylori virulence factors in development of gastric carcinoma. Future Microbiol 2015; 10:1505-16. [PMID: 26346770 DOI: 10.2217/fmb.15.72] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Helicobacter pylori plays a vital role in the pathogenesis of gastric carcinoma. However, only a relatively small proportion of individuals infected with H. pylori develop gastric carcinoma. Differences in the incidence of gastric carcinoma among infected individuals can be explained, at least partly, by the different genotypes of H. pylori virulence factors. Thus far, many virulence factors of H. pylori, such as Cag PAI, VacA, OMPs and DupA, have been reported to be involved in the development of gastric cancer. The risk of developing gastric cancer during H. pylori infection is affected by specific host-microbe interactions that are independent of H. pylori virulence factors. In this review, we discuss virulence factors of H. pylori and their role in the development of gastric carcinoma that will provide further understanding of the biological interactions of H. pylori with the host.
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Affiliation(s)
- Ming-Yi Wang
- Department of Clinical Lab, Weihai Municipal Hospital, Dalian Medical University, Weihai, Shandong, 264200, PR China
| | - Xiao-Fei Liu
- Department of Laboratory Medicine, General Hospital of Ji'nan Military Region of PLA, Ji'nan, Shandong Province, 250031, PR China
| | - Xiao-Zhong Gao
- Department of Gastroenterology, Weihai Municipal Hospital, Dalian Medical University, Weihai, Shandong, 264200, PR China
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Romo-González C, Consuelo-Sánchez A, Camorlinga-Ponce M, Velázquez-Guadarrama N, García-Zúñiga M, Burgueño-Ferreira J, Coria-Jiménez R. Plasticity Region Genes jhp0940, jhp0945, jhp0947, and jhp0949 of Helicobacter pylori in Isolates from Mexican Children. Helicobacter 2015; 20:231-7. [PMID: 25735460 DOI: 10.1111/hel.12194] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND The genes jhp0940, jhp0945, jhp0947, and jhp0949 belong to the plasticity region of the Helicobacter pylori genome. Due to their prevalence in isolates from patients with gastritis, duodenal ulcer, and gastric cancer, they have been proposed as markers of gastroduodenal diseases. These genes are associated with pro-inflammatory cytokine induction through the NF-κB activation pathway. Nevertheless, the status of these genes is unknown in H. pylori isolates from children. The aim of the present work was to determine the frequency of the jhp0940-jhp0945-jhp0947-jhp0949 genes in H. pylori isolates from children. MATERIALS AND METHODS We identified the jhp0940, jhp0945, jhp0947, and jhp0949 genes and the relationship of each with the virulence factors cagA, cagPAI, and dupA by PCR in 49 isolates of H. pylori from children. The results were corroborated using dot blots. In addition, we compared the prevalence of these genes with the prevalence in adults. RESULTS The prevalence of jhp0940 (53.1%), jhp0945 (44.9%), jhp0947 (77.6%), and jhp0949 (83.7%) was determined in the isolates from children, as was the prevalence of the virulence genes cagA (63.3%), cagPAI (71.4%), and dupA (37.5%). No association was found between the four genes of the plasticity region and the virulence genes. The presence of the intact locus integrated by jhp0940-jhp0945-jhp0947-jhp0949 was very common among the isolates from children. CONCLUSION The genes jhp0940, jhp0947, and jhp0949 were present in more than 50% of the H. pylori isolates, and the joint presence of jhp0940-jhp0945-jhp0947-jhp0949 was very frequent. The frequency of these genes in isolates from children could contribute to the virulence of H. pylori and the evolution of the infection.
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Affiliation(s)
| | - Alejandra Consuelo-Sánchez
- Gastroenterology & Nutrition Department, Children's Hospital of Mexico "Federico Gómez", SSA, México, D.F., México
| | - Margarita Camorlinga-Ponce
- Infectious Diseases Research Unit, Instituto Mexicano del Seguro Social, Mexico City, Mexico, CMN Siglo XXI, IMSS, México, D.F., México
| | | | | | - Juan Burgueño-Ferreira
- International Maize and Wheat Improvement Center, Biometrics and Statistics Unit, Mexico, Mexico
| | - Rafael Coria-Jiménez
- Experimental Bacteriology, National Institute of Pediatrics, SSA, México, D.F., México
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Wang MY, Shao C, Li J, Yang YC, Wang SB, Hao JL, Wu CM, Gao XZ, Shao SH. Helicobacter pylori with the Intact dupA Cluster is more Virulent than the Strains with the Incomplete dupA Cluster. Curr Microbiol 2015; 71:16-23. [PMID: 25847580 DOI: 10.1007/s00284-015-0812-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2014] [Accepted: 02/23/2015] [Indexed: 12/14/2022]
Abstract
The duodenal ulcer promoting gene (dupA), located in the plasticity region of Helicobacter pylori (H. pylori), is predicted to form a type IV secretory system (T4SS) with vir genes around dupA. In the study, we investigated the association between the dupA cluster status and the virulence of H. pylori in a littoral region of Northeast China. Two hundred and sixty-two H. pylori strains isolated from the chronic gastritis were examined to evaluate the dupA cluster status, cag PAI genes and vacA genotype using PCR and Western blot. Histopathologic evaluations of biopsy specimens were performed to analysis the association between the dupA cluster and the inflammatory response. IL-8 productions in gastric mucosa and from GES-1 cells co-cultured with H. pylori were measured, respectively, to analysis the association between the dupA cluster status and IL-8 production. We found that gastric mucosal inflammatory cell infiltration was significantly higher in patients with dupA-positive H. pylori, including H. pylori with complete dupA cluster (2.71 ± 0.79) and incomplete dupA cluster (2.09 ± 0.61) than in patients with dupA-negative strain (1.73 ± 0.60, p < 0.01), whereas no significant difference in the gastric mucosal atrophy was found according to the status of dupA cluster. Gastric mucosal IL-8 levels were higher in the complete dupA cluster group than in other groups (p < 0.01), and IL-8 production from GES-1 cells was also significantly higher in strains with a complete dupA cluster (1527.9 ± 180.0 pg/ml) than in those with an incomplete dupA cluster (1229.4 ± 75.3 pg/ml, p < 0.01) or those with dupA negative (1201.9 ± 92.3 pg/ml, p < 0.01). In conclusion, the complete dupA cluster in H. pylori is associated with inflammatory cell infiltration and IL-8 secretion, and H. pylori strain with a complete dupA cluster seems to be more virulent than other strains with the incomplete dupA cluster or dupA negative.
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Affiliation(s)
- Ming-yi Wang
- School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, People's Republic of China
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Abstract
Helicobacter pylori is human gastric pathogen that causes chronic and progressive gastric mucosal inflammation and is responsible for the gastric inflammation-associated diseases, gastric cancer and peptic ulcer disease. Specific outcomes reflect the interplay between host-, environmental- and bacterial-specific factors. Progress in understanding putative virulence factors in disease pathogenesis has been limited and many false leads have consumed scarce resources. Few in vitro-in vivo correlations or translational applications have proved clinically relevant. Reported virulence factor-related outcomes reflect differences in relative risk of disease rather than specificity for any specific outcome. Studies of individual virulence factor associations have provided conflicting results. Since virulence factors are linked, studies of groups of putative virulence factors are needed to provide clinically useful information. Here, the authors discuss the progress made in understanding the role of H. pylori virulence factors CagA, vacuolating cytotoxin, OipA and DupA in disease pathogenesis and provide suggestions for future studies.
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Affiliation(s)
- Yoshio Yamaoka
- Department of Environmental & Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan
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You Y, He L, Zhang M, Zhang J. Comparative genomics of a Helicobacter pylori isolate from a Chinese Yunnan Naxi ethnic aborigine suggests high genetic divergence and phage insertion. PLoS One 2015; 10:e0120659. [PMID: 25799515 PMCID: PMC4370579 DOI: 10.1371/journal.pone.0120659] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2014] [Accepted: 01/07/2015] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori is a common pathogen correlated with several severe digestive diseases. It has been reported that isolates associated with different geographic areas, different diseases and different individuals might have variable genomic features. Here, we describe draft genomic sequences of H. pylori strains YN4-84 and YN1-91 isolated from patients with gastritis from the Naxi and Han populations of Yunnan, China, respectively. The draft sequences were compared to 45 other publically available genomes, and a total of 1059 core genes were identified. Genes involved in restriction modification systems, type four secretion system three (TFS3) and type four secretion system four (TFS4), were identified as highly divergent. Both YN4-84 and YN1-91 harbor intact cag pathogenicity island (cagPAI) and have EPIYA-A/B/D type at the carboxyl terminal of cagA. The vacA gene type is s1m2i1. Another major finding was a 32.5-kb prophage integrated in the YN4-84 genome. The prophage shares most of its genes (30/33) with Helicobacter pylori prophage KHP30. Moreover, a 1,886 bp transposable sequence (IS605) was found in the prophage. Our results imply that the Naxi ethnic minority isolate YN4-84 and Han isolate YN1-91 belong to the hspEAsia subgroup and have diverse genome structure. The genome has been extensively modified in several regions involved in horizontal DNA transfer. The important roles played by phages in the ecology and microevolution of H. pylori were further emphasized. The current data will provide valuable information regarding the H. pylori genome based on historic human migrations and population structure.
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Affiliation(s)
- Yuanhai You
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
| | - Lihua He
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
| | - Maojun Zhang
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
| | - Jianzhong Zhang
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
- * E-mail:
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Souod N, Sarshar M, Dabiri H, Momtaz H, Kargar M, Mohammadzadeh A, Abdi S. The study of the oipA and dupA genes in Helicobacter pylori strains and their relationship with different gastroduodenal diseases. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2015; 8:S47-53. [PMID: 26171137 PMCID: PMC4495424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/21/2015] [Accepted: 05/29/2015] [Indexed: 11/07/2022]
Abstract
AIM The purpose of this investigation was to determine the oipA and dupA genes of Helicobacter pylori isolates from west of Iran; Chaharmahalo Bakhtiyari region and find their relationship with the severity of the gastroduodenal diseases. BACKGROUND Helicobacter pylori is an organism responsible for many gastroduodenal diseases. Many studies suggest that genetic diversity in H . pylori virulence factors such as oipA and dupA genes is high among isolates of different geographic regions and may cause more severe diseases. PATIENTS AND METHODS In this cross-sectional study, gastric biopsy specimens were taken from 150 patients suffering from gastroduodenal diseases. The presence of ureC, dupA and oipA genes was tested by polymerase chain reaction (PCR). RESULTS Overall, 123 (82%) H. pylori strains were isolated from 150 specimens. dupA gene was detected in 41 (33.33%) H.pylori-positive specimens. There was a reverse correlation between this gene and gastric cancer. The oipA gene was found in 88 (71.54%) samples and statistically there was no association between this gene and gastric disorders. As statistical analyses revealed, the presence of the dupA was more common in isolates with the oipA negative. CONCLUSION Based on our findings, the presence of dupA gene can be considered as a marker for the onset of severe diseases. However, the oipA gene cannot be regarded for prediction of gastroenterology diseases. Meanwhile, extended molecular epidemiology researches in other populations are recommended.
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Affiliation(s)
- Negar Souod
- Young Researchers club, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Meysam Sarshar
- Department of Public Health and Infectious Diseases, Sapienza, University of Rome, Rome, Italy
| | - Hossein Dabiri
- Department of Clinical Microbiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hassan Momtaz
- Department of Microbiology, ShahreKord Branch, Islamic Azad University, ShahreKord, Iran
| | - Mohammad Kargar
- Department of Microbiology, Jahrom Branch, Islamic Azad University, Jahrom, Iran
| | - Alireza Mohammadzadeh
- Department of Microbiology, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Saeed Abdi
- Gastroenterology and Liver Diseases Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran Iran
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Analysis of Genomic Diversity among Helicobacter pylori Strains Isolated from Iranian Children by Pulsed Field Gel Electrophoresis. IRANIAN JOURNAL OF PEDIATRICS 2014; 24:703-9. [PMID: 26019775 PMCID: PMC4442831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/02/2014] [Accepted: 11/11/2014] [Indexed: 11/04/2022]
Abstract
OBJECTIVE Presence of genomic diversity among Helicobacter pylori (H. pylori) strains have been suggested by numerous investigators. Little is known about diversity of H. pylori strains isolated from Iranian children and their association with virulence of the strains. Our purpose was to assess the degree of genomic diversity among H. pylori strains isolated from Iranian-children, on the basis of vacA genotype, cagA status of the strains, sex, age as well as the pathological status of the patients. METHODS Genomic DNA from 44 unrelated H. pylori strains isolated during 1997-2009, was examined by pulse-field gel electrophoresis (PFGE). Pathological status of the patients was performed according to the modified Sydney-system and genotype/status of vacA/cagA genes was determined by PCR. PFGE was performed using XbaI restriction-endonuclease and the field inversion-gel electrophoresis system. FINDINGS No significant relationship was observed between the patterns of PFGE and the cagA/vacA status/genotype. Also no relationship was observed between age, sex, and pathological status of the children and the PFGE patterns of their isolates. Similar conclusion was obtained by Total Lab software. However, more relationship was observed between the strains isolated in the close period (1997-2009, 2001-2003, 2005-2007, and 2007-2009) and more difference was observed among those obtained in the distant periods (1997 and 2009). CONCLUSION H. pylori strains isolated from children in Iran are extremely diverse and this diversity is not related to their virulence characteristics. Occurrence of this extreme diversity may be related to adaptation of H. pylori strains to variable living conditions during transmission between various host individuals.
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Crystal structure confirmation of JHP933 as a nucleotidyltransferase superfamily protein from Helicobacter pylori strain J99. PLoS One 2014; 9:e104609. [PMID: 25101777 PMCID: PMC4125220 DOI: 10.1371/journal.pone.0104609] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Accepted: 07/09/2014] [Indexed: 01/25/2023] Open
Abstract
Helicobacter pylori is a well-known pathogen involved in the development of peptic ulcer, gastric adenocarcinoma and other forms of gastric cancer. Recently, there has been more considerable interest in strain-specific genes located in plasticity regions with great genetic variability. However, little is known about many of these genes. Studies suggested that certain genes in this region may play key roles in the pathogenesis of H. pylori-associated gastroduodenal diseases. JHP933, a conserved putative protein of unknown function, is encoded by the gene in plasticity region of H. pylori strain J99. Here we have determined the structure of JHP933. Our work demonstrates that JHP933 is a nucleotidyltransferase superfamily protein with a characteristic αβαβαβα topology. A superposition demonstrates overall structural homology of the JHP933 N-terminal fragment with lincosamide antibiotic adenylyltransferase LinA and identifies a possible substrate-binding cleft of JHP933. Furthermore, through structural comparison with LinA and LinB, we pinpoint conservative active site residues which may contribute to divalent ion coordination and substrate binding.
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Tenguria S, Ansari SA, Khan N, Ranjan A, Devi S, Tegtmeyer N, Lind J, Backert S, Ahmed N. Helicobacter pylori cell translocating kinase (CtkA/JHP0940) is pro-apoptotic in mouse macrophages and acts as auto-phosphorylating tyrosine kinase. Int J Med Microbiol 2014; 304:1066-76. [PMID: 25172221 DOI: 10.1016/j.ijmm.2014.07.017] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Revised: 06/26/2014] [Accepted: 07/28/2014] [Indexed: 12/16/2022] Open
Abstract
The Helicobacter pylori gene JHP0940 has been shown to encode a serine/threonine kinase which can induce cytokines in gastric epithelial cells relevant to chronic gastric inflammation. Here we demonstrate that JHP0940 can be secreted by the bacteria, triggers apoptosis in cultured mouse macrophages and acts as an auto-phosphorylating tyrosine kinase. Recombinant JHP0940 protein was found to decrease the viability of RAW264.7 cells (a mouse macrophage cell line) up to 55% within 24h of co-incubation. The decreased cellular viability was due to apoptosis, which was confirmed by TUNEL assay and Fas expression analysis by flow-cytometry. Further, we found that caspase-1 and IL-1beta were activated upon treatment with JHP0940. These results point towards possible action through the host inflammasome. Our in vitro studies using tyrosine kinase assays further demonstrated that JHP0940 acts as auto-phosphorylating tyrosine kinase and induces pro-inflammatory cytokines in RAW264.7 cells. Upon exposure with JHP0940, these cells secreted IL-1beta, TNF-alpha and IL-6, in a dose- and time-dependent manner, as detected by ELISA and transcript profiling by q-RT-PCR. The pro-inflammatory, pro-apoptotic and other regulatory responses triggered by JHP0940 lead to the assumption of its possible role in inducing chronic inflammation for enhanced bacterial persistence and escape from host innate immune responses by apoptosis of macrophages.
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Affiliation(s)
- Shivendra Tenguria
- Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad 500046, India
| | - Suhail A Ansari
- Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad 500046, India
| | - Nooruddin Khan
- Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad 500046, India
| | - Amit Ranjan
- Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad 500046, India
| | - Savita Devi
- Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad 500046, India
| | - Nicole Tegtmeyer
- Division of Microbiology, Department of Biology, Friedrich Alexander University Nuremberg, D-91058 Erlangen, Germany
| | - Judith Lind
- Division of Microbiology, Department of Biology, Friedrich Alexander University Nuremberg, D-91058 Erlangen, Germany
| | - Steffen Backert
- Division of Microbiology, Department of Biology, Friedrich Alexander University Nuremberg, D-91058 Erlangen, Germany
| | - Niyaz Ahmed
- Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad 500046, India.
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Talebi Bezmin Abadi A. The Helicobacter pylori dupA: A Novel Biomarker for Digestive Diseases. Front Med (Lausanne) 2014; 1:13. [PMID: 25767798 PMCID: PMC4341267 DOI: 10.3389/fmed.2014.00013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2014] [Accepted: 05/15/2014] [Indexed: 12/25/2022] Open
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Yoon JY, Lee SJ, Kim DJ, Lee BJ, Yang JK, Suh SW. Crystal structure of JHP933 fromHelicobacter pyloriJ99 shows two-domain architecture with a DUF1814 family nucleotidyltransferase domain and a helical bundle domain. Proteins 2014; 82:2275-81. [DOI: 10.1002/prot.24572] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2014] [Revised: 03/03/2014] [Accepted: 03/21/2014] [Indexed: 01/26/2023]
Affiliation(s)
- Ji Young Yoon
- Department of Chemistry; College of Natural Sciences, Seoul National University; Seoul 151-742 Republic of Korea
| | - Sang Jae Lee
- The Research Institute of Pharmaceutical Sciences; College of Pharmacy, Seoul National University, Gwanak-gu; Seoul 151-742 Republic of Korea
| | - Do Jin Kim
- Department of Chemistry; College of Natural Sciences, Seoul National University; Seoul 151-742 Republic of Korea
| | - Bong-Jin Lee
- The Research Institute of Pharmaceutical Sciences; College of Pharmacy, Seoul National University, Gwanak-gu; Seoul 151-742 Republic of Korea
| | - Jin Kuk Yang
- Department of Chemistry; College of Natural Sciences, Soongsil University; Seoul 156-743 Republic of Korea
| | - Se Won Suh
- Department of Chemistry; College of Natural Sciences, Seoul National University; Seoul 151-742 Republic of Korea
- Department of Biophysics and Chemical Biology; College of Natural Sciences, Seoul National University; Seoul 151-742 Republic of Korea
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Momtaz H, Dabiri H, Souod N, Gholami M. Study of Helicobacter pylori genotype status in cows, sheep, goats and human beings. BMC Gastroenterol 2014; 14:61. [PMID: 24708464 PMCID: PMC4234145 DOI: 10.1186/1471-230x-14-61] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2013] [Accepted: 03/21/2014] [Indexed: 12/15/2022] Open
Abstract
Background Helicobacter pylori is one of the most controversial bacteria in the world causing diverse gastrointestinal diseases. The transmission way of this bacterium still remains unknown. The possibility of zoonotic transmission of H. pylori has been suggested, but is not proven in nonprimate reservoirs. In the current survey, we investigate the presence of H. pylori in cow, sheep and goat stomach, determine the bacterium virulence factors and finally compare the human H. pylori virulence factors and animals in order to examine whether H. pylori might be transmitted from these animals to human beings. Methods This cross- sectional study was performed on 800 gastric biopsy specimens of cows, sheep, goats and human beings. The PCR assays was performed to detection of H. pylori, vacA and cagA genes. The PCR products of Ruminant’s samples with positive H. pylori were subjected to DNA sequencing analysis. Statistical tests were applied for data analysis. Results Overall 6 (3%) cows, 32 (16%) sheep and 164 (82%) human beings specimens were confirmed to be H. pylori positive; however we were not able to detect this bacterium in all 200 goat samples. The vacA s1a/m1a was the predominant H. pylori genotype in all three kinds of studied population. There was 3.4–8.4% variability and 92.9-98.5% homology between sheep and human samples. Conclusions Considering the high sequence homology among DNA of H. pylori isolated from sheep and human, our data suggest that sheep may act as a reservoir for H. pylori and in the some extent share the ancestral host for the bacteria with human.
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Affiliation(s)
| | | | - Negar Souod
- Young Researchers and Elite club, Central Tehran Branch, Islamic Azad University, P,O,Box: 13185-768, Tehran, Iran.
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Roesler BM, Rabelo-Gonçalves EMA, Zeitune JMR. Virulence Factors of Helicobacter pylori: A Review. CLINICAL MEDICINE INSIGHTS. GASTROENTEROLOGY 2014; 7:9-17. [PMID: 24833944 PMCID: PMC4019226 DOI: 10.4137/cgast.s13760] [Citation(s) in RCA: 99] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/01/2013] [Revised: 02/16/2014] [Accepted: 02/17/2014] [Indexed: 12/20/2022]
Abstract
Helicobacter pylori is a spiral-shaped Gram-negative bacterium that colonizes the human stomach and can establish a long-term infection of the gastric mucosa, a condition that affects the relative risk of developing various clinical disorders of the upper gastrointestinal tract, such as chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma. H. pylori presents a high-level of genetic diversity, which can be an important factor in its adaptation to the host stomach and also for the clinical outcome of infection. There are important H. pylori virulence factors that, along with host characteristics and the external environment, have been associated with the different occurrences of diseases. This review is aimed to analyzing and summarizing the main of them and possible associations with the clinical outcome.
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Affiliation(s)
- Bruna M Roesler
- Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil. ; Center of Diagnosis of Digestive Diseases, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil
| | - Elizabeth M A Rabelo-Gonçalves
- Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil. ; Center of Diagnosis of Digestive Diseases, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil
| | - José M R Zeitune
- Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil. ; Center of Diagnosis of Digestive Diseases, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil
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Devi S, Ansari SA, Vadivelu J, Mégraud F, Tenguria S, Ahmed N. Helicobacter pylori antigen HP0986 (TieA) interacts with cultured gastric epithelial cells and induces IL8 secretion via NF-κB mediated pathway. Helicobacter 2014; 19:26-36. [PMID: 24205801 DOI: 10.1111/hel.12100] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The envisaged roles and partly understood functional properties of Helicobacter pylori protein HP0986 are significant in the context of proinflammatory and or proapoptotic activities, the two important facilitators of pathogen survival and persistence. In addition, sequence analysis of this gene predicts a restriction endonuclease function which remained unknown thus far. To evaluate the role of HP0986 in gastric inflammation, we studied its expression profile using a large number of clinical isolates but a limited number of biopsies and patient sera. Also, we studied antigenic role of HP0986 in altering cytokine responses of human gastric epithelial (AGS) cells including its interaction with and localization within the AGS cells. MATERIALS AND METHODS For in vitro expression study of HP0986, 110 H. pylori clinical isolates were cultured from patients with functional dyspepsia. For expression analysis by qRT PCR of HP0986, 10 gastric biopsy specimens were studied. HP0986 was also used to detect antibodies in patient sera. AGS cells were incubated with recombinant HP0986 to determine cytokine response and NF-κB activation. Transient transfection with HP0986 cloned in pEGFPN1 was used to study its subcellular localization or homing in AGS cells. RESULTS Out of 110 cultured H. pylori strains, 34 (31%) were positive for HP0986 and this observation was correlated with in vitro expression profiles. HP0986 mRNA was detected in 7 of the 10 biopsy specimens. Further, HP0986 induced IL-8 secretion in gastric epithelial cells in a dose and time-dependent manner via NF-κB pathway. Serum antibodies against HP0986 were positively associated with H. pylori positive patients. Transient transfection of AGS cells revealed both cytoplasmic and nuclear localization of HP0986. CONCLUSION HP0986 was moderately prevalent in clinical isolates and its expression profile in cultures and gastric biopsies points to its being naturally expressed. Collective observations including the induction of IL-8 via TNFR1 and NF-κB, subcellular localization, and seropositivity data point to a significant role of HP0986 in gastroduodenal inflammation. We propose to name the HP0986 gene/protein as 'TNFR1 interacting endonuclease A (TieA or tieA)'.
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Affiliation(s)
- Savita Devi
- Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad, 500046, India
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Abstract
Helicobacter pylori (H. pylori) infection is linked to various gastroduodenal diseases; however, only a small fraction of these patients develop associated diseases. Despite the high prevalence of H. pylori infection in Africa and South Asia, the incidence of gastric cancer in these areas is much lower than those in other countries. The incidence of gastric cancer tends to decrease from north to south in East Asia. Such geographical differences in the pathology can be explained, at least in part, by the presence of different types of H. pylori virulence factors in addition to host and environmental factors. Virulence factors of H. pylori, such as CagA, VacA, DupA, IceA, OipA and BabA, have been demonstrated to be the predictors of severe clinical outcomes. Interestingly, a meta-analysis showed that CagA seropositivity was associated with gastric cancer compared with gastritis, even in East Asian countries where almost the strains possess cagA. Another meta-analysis also confirmed the significance of vacA, dupA and iceA. However, it is possible that additional important pathogenic genes may exist because H. pylori consists of approximately 1600 genes. Despite the advances in our understanding of the development of H. pylori infection-related diseases, further work is required to clarify the roles of H. pylori virulence factors.
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Affiliation(s)
- Seiji SHIOTA
- Department of Environmental and Preventive Medicine, Yufu-City, Oita, Japan
,Department of General Medicine, Oita University Faculty of Medicine, Yufu-City, Oita, Japan
| | - Rumiko SUZUKI
- Department of Environmental and Preventive Medicine, Yufu-City, Oita, Japan
| | - Yoshio YAMAOKA
- Department of Environmental and Preventive Medicine, Yufu-City, Oita, Japan
,Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas, USA
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Wang MY, Chen C, Gao XZ, Li J, Yue J, Ling F, Wang XC, Shao SH. Distribution of Helicobacter pylori virulence markers in patients with gastroduodenal diseases in a region at high risk of gastric cancer. Microb Pathog 2013; 59-60:13-8. [PMID: 23583809 DOI: 10.1016/j.micpath.2013.04.001] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2012] [Revised: 03/24/2013] [Accepted: 04/01/2013] [Indexed: 02/06/2023]
Abstract
ABSTRACT BACKGROUND Helicobacter pylori (H. pylori) is a major human pathogen that is responsible for various gastroduodenal diseases. We investigated the prevalence of H. pylori virulence markers in a region at high risk of gastric cancer. METHODS One hundred and sixteen H. pylori strains were isolated from patients with gastroduodenal diseases. cagA, the cagA 3' variable region, cagPAI genes, vacA, and dupA genotypes were determined by PCR, and some amplicons of the cagA 3' variable region, cagPAI genes and dupA were sequenced. RESULTS cagA was detected in all strains. The cagA 3' variable region of 85 strains (73.3%) was amplified, and the sequences of 24 strains were obtained including 22 strains possessing the East Asian-type. The partial cagPAI presented at a higher frequency in chronic gastritis (44.4%) than that of the severe clinical outcomes (9.7%, p < 0.001). The most prevalent vacA genotypes were s1a/m2 (48.3%) and s1c/m2 (13.8%). Thirty-six strains (31.0%) possessed dupA and sequencing of dupA revealed an ORF of 2449-bp. The prevalence of dupA was significantly higher in strains from patients with the severe clinical outcomes (40.3%) than that from chronic gastritis (20.4%, p = 0.02). CONCLUSION The high rate of East Asian-type cagA, intact cagPAI, virulent vacA genotypes, and the intact long-type dupA may underlie the high risk of gastric cancer in the region.
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Affiliation(s)
- Ming-yi Wang
- School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China
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Takahashi A, Shiota S, Matsunari O, Watada M, Suzuki R, Nakachi S, Kinjo N, Kinjo F, Yamaoka Y. Intact long-type dupA as a marker for gastroduodenal diseases in Okinawan subpopulation, Japan. Helicobacter 2013; 18:66-72. [PMID: 23067336 PMCID: PMC3545078 DOI: 10.1111/j.1523-5378.2012.00994.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Helicobacter pylori dupA can be divided into two types according to the presence or absence of the mutation. In addition, full-sequenced data revealed that dupA has two types with different lengths depend on the presence of approximately 600 bp in the putative 5' region (presence; long-type and absence; short-type), which has not been taken into account in previous studies. METHODS A total of 319 strains isolated from Okinawa, the south islands of Japan, were included. The status of dupA and cagA was determined by polymerase chain reaction. The presence of mutations in long-type dupA was determined by DNA sequencing. RESULTS The prevalence of long-type dupA was 26.3% (84/319). Sequence analysis showed that there were only six cases (7.1%) with point mutations lead to stop codon among 84 long-type dupA strains studied. Interestingly, intact long-type dupA without frameshift mutation, but not short-type dupA, was significantly associated with gastric ulcer and gastric cancer than gastritis (p = .001 and p = .019, respectively). After adjustment by age, gender, and cagA, the presence of intact long-type dupA was significantly associated with gastric ulcer and gastric cancer compared with gastritis (odds ratio [OR] = 3.35, 95% confidence interval [CI] = 1.55-7.24 and OR = 4.14, 95% CI = 1.23-13.94, respectively). CONCLUSIONS Intact long-type dupA is a real virulence marker for severe outcomes in Okinawa, Japan. The previous information gained from PCR-based methods without taking long-type dupA into account must be interpreted with caution.
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Affiliation(s)
- Ayaka Takahashi
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5569, Japan
| | - Seiji Shiota
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5569, Japan
| | - Osamu Matsunari
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5569, Japan
| | - Masahide Watada
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5569, Japan
| | - Rumiko Suzuki
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5569, Japan
| | - Saori Nakachi
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5569, Japan
| | - Nagisa Kinjo
- Department of Endoscopy, University Hospital, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan
| | - Fukunori Kinjo
- Department of Endoscopy, University Hospital, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5569, Japan,Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas, 77030 USA,Corresponding author: Yoshio YamaokaMD, PhD, Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan, Tel: +81-97-586-5740; Fax: +81-97-586-5749,
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Genome of Helicobacter pylori strain XZ274, an isolate from a tibetan patient with gastric cancer in China. J Bacteriol 2012; 194:4146-7. [PMID: 22815458 DOI: 10.1128/jb.00804-12] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
The infection rate of Helicobacter pylori is high all over the world, especially in the Chinese Tibetan Plateau. Here, we report the genome sequence of Helicobacter pylori strain XZ274 isolated from a Tibetan patient with gastric cancer. The strain contains 1,634,138 bp with 1,654 coding sequences and a pXZ274 plasmid of 22,406 bp with 26 coding sequences. This is the first complete genome sequence of Helicobacter pylori from the Tibetan Plateau in China.
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