|
1
|
Elbehiry A, Marzouk E, Abalkhail A, Sindi W, Alzahrani Y, Alhifani S, Alshehri T, Anajirih NA, ALMutairi T, Alsaedi A, Alzaben F, Alqrni A, Draz A, Almuzaini AM, Aljarallah SN, Almujaidel A, Abu-Okail A. Pivotal role of Helicobacter pylori virulence genes in pathogenicity and vaccine development. Front Med (Lausanne) 2025; 11:1523991. [PMID: 39850097 PMCID: PMC11756510 DOI: 10.3389/fmed.2024.1523991] [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: 11/06/2024] [Accepted: 12/13/2024] [Indexed: 01/25/2025] Open
Abstract
One of the most prevalent human infections is Helicobacter pylori (H. pylori), which affects more than half of the global population. Although H. pylori infections are widespread, only a minority of individuals develop severe gastroduodenal disorders. The global resistance of H. pylori to antibiotics has reached concerning levels, significantly impacting the effectiveness of treatment. Consequently, the development of vaccines targeting virulence factors may present a viable alternative for the treatment and prevention of H. pylori infections. This review aims to provide a comprehensive overview of the current understanding of H. pylori infection, with a particular focus on its virulence factors, pathophysiology, and vaccination strategies. This review discusses various virulence factors associated with H. pylori, such as cytotoxin-associated gene A (cagA), vacuolating cytotoxin gene (vacA), outer membrane proteins (OMPs), neutrophil-activated protein (NAP), urease (ure), and catalase. The development of vaccines based on these virulence characteristics is essential for controlling infection and ensuring long-lasting protection. Various vaccination strategies and formulations have been tested in animal models; however, their effectiveness and reproducibility in humans remain uncertain. Different types of vaccines, including vector-based vaccines, inactivated whole cells, genetically modified protein-based subunits, and multiepitope nucleic acid (DNA) vaccines, have been explored. While some vaccines have demonstrated promising results in murine models, only a limited number have been successfully tested in humans. This article provides a thorough evaluation of recent research on H. pylori virulence genes and vaccination methods, offering valuable insights for future strategies to address this global health challenge.
Collapse
Affiliation(s)
- Ayman Elbehiry
- Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Eman Marzouk
- Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Adil Abalkhail
- Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Wael Sindi
- Department of Population, Public and Environmental Health, General Administration of Health Services, Ministry of Defense, Riyadh, Saudi Arabia
| | - Yasir Alzahrani
- Department of Psychiatry, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | - Salem Alhifani
- Department of Psychiatry, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | - Turki Alshehri
- Department of Dental, Alhada Armed Forces Hospital, Taif, Saudi Arabia
| | - Nuha Abdulaziz Anajirih
- Department of Medical Emergency Services, Faculty of Health Sciences, Umm Al-Qura University, Al-Qunfudah, Saudi Arabia
| | - Turki ALMutairi
- Department of Education and Training, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
| | - Ahmad Alsaedi
- Department of Education and Training, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
| | - Feras Alzaben
- Department of Food Service, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | - Abdullah Alqrni
- Department of Preventive Medicine, King Fahad Armed Hospital, Jeddah, Saudi Arabia
| | - Abdelmaged Draz
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Abdulaziz M. Almuzaini
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Sahar N. Aljarallah
- Department of Pharmacy Sciences, College of Pharmacy, AlMaarefa University, Riyadh, Saudi Arabia
| | - Abdulrahman Almujaidel
- Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Akram Abu-Okail
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| |
Collapse
|
|
2
|
Xu JY, Dong HH, Liao LJ, Yang SX, Wang LY, Chen H, Luo P, Huang L, Guan AX, Huang YQ. Deoxyshikonin: a promising lead drug grass against drug resistance or sensitivity to Helicobacter pylori in an acidic environment. Antimicrob Agents Chemother 2024; 68:e0095924. [PMID: 39171918 PMCID: PMC11460997 DOI: 10.1128/aac.00959-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 07/29/2024] [Indexed: 08/23/2024] Open
Abstract
Helicobacter pylori (H. pylori) is closely associated with the diseases such as gastric sinusitis, peptic ulcers, and gastric adenocarcinoma. Its drug resistance is very severe, and new antibiotics are urgently needed. Nine comfrey compounds were screened by antimicrobial susceptibility testing, among which deoxyshikonin had the best inhibitory effect, with a minimum inhibitory concentration (MIC) of 0.5-1 µg/mL. In addition, deoxyshikonin also has a good antibacterial effect in an acidic environment, it is highly safe, and H. pylori does not readily develop drug resistance. Through in vivo experiments, it was proven that deoxyshikonin (7 mg/kg) had a beneficial therapeutic effect on acute gastritis in mice infected with the multidrug-resistant H. pylori BS001 strain. After treatment with desoxyshikonin, colonization of H. pylori in the gastric mucosa of mice was significantly reduced, gastric mucosal damage was repaired, inflammatory factors were reduced, and the treatment effect was better than that of standard triple therapy. Therefore, deoxyshikonin is a promising lead drug to solve the difficulty of drug resistance in H. pylori, and its antibacterial mechanism may be to destroy the biofilm and cause an oxidation reaction.
Collapse
Affiliation(s)
- Jia-yin Xu
- Guangxi Technology
Innovation Cooperation Base of Prevention and Control Pathogenic
Microbes with Drug Resistance, Youjiang Medical University for
Nationalities, Baise,
China
| | - Hui-hua Dong
- Guangxi Technology
Innovation Cooperation Base of Prevention and Control Pathogenic
Microbes with Drug Resistance, Youjiang Medical University for
Nationalities, Baise,
China
| | - Li-juan Liao
- Guangxi Technology
Innovation Cooperation Base of Prevention and Control Pathogenic
Microbes with Drug Resistance, Youjiang Medical University for
Nationalities, Baise,
China
| | - Shi-xian Yang
- Affiliated Hospital of
Youjiang Medical University for
Nationalities, Baise,
China
- Guangxi Zhuang
Autonomous Region Engineering Research Center of Clinical Prevention and
Control Technology and Leading Drug for Microorganisms with Drug
Resistance in Border Ethnic Areas,
Baise, China
| | - Lu-yao Wang
- Guangxi Technology
Innovation Cooperation Base of Prevention and Control Pathogenic
Microbes with Drug Resistance, Youjiang Medical University for
Nationalities, Baise,
China
| | - Hao Chen
- Department of
Pathology, School of Basic Medical Sciences, Wannan Medical
College, Wuhu,
China
| | - Peipei Luo
- Department of
Gastroenterology, Wujin People’s Hospital affiliated to JiangSu
University, Changzhou,
China
| | - Liang Huang
- Guangxi Technology
Innovation Cooperation Base of Prevention and Control Pathogenic
Microbes with Drug Resistance, Youjiang Medical University for
Nationalities, Baise,
China
| | - Ai-xing Guan
- Affiliated Hospital of
Youjiang Medical University for
Nationalities, Baise,
China
- Guangxi Zhuang
Autonomous Region Engineering Research Center of Clinical Prevention and
Control Technology and Leading Drug for Microorganisms with Drug
Resistance in Border Ethnic Areas,
Baise, China
| | - Yan-Qiang Huang
- Affiliated Hospital of
Youjiang Medical University for
Nationalities, Baise,
China
- Guangxi Zhuang
Autonomous Region Engineering Research Center of Clinical Prevention and
Control Technology and Leading Drug for Microorganisms with Drug
Resistance in Border Ethnic Areas,
Baise, China
- Guangxi Clinical
Medical Research Center for Hepatobiliary
Diseases, Liuzhou,
China
| |
Collapse
|
|
3
|
Fathi Kisomi M, Yadegar A, Shekari T, Amin M, Llopis-Lorente A, Liu C, Haririan I, Aghdaei HA, Shokrgozar MA, Zali MR, Rad-Malekshahi M, Miri AH, Hamblin MR, Wacker MG. Unveiling the potential role of micro/nano biomaterials in the treatment of Helicobacter pylori infection. Expert Rev Anti Infect Ther 2024; 22:613-630. [PMID: 39210553 DOI: 10.1080/14787210.2024.2391910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 08/09/2024] [Indexed: 09/04/2024]
Abstract
INTRODUCTION Helicobacter pylori causes stubborn infections and leads to a variety of stomach disorders, such as peptic ulcer, chronic atrophic gastritis, and gastric cancer. Although antibiotic-based approaches have been widely used against H. pylori, some challenges such as antibiotic resistance are increasing in severity. Therefore, simpler but more effective strategies are needed. AREAS COVERED In this review, basic information on functionalized and non-functionalized micro/nano biomaterials and routes of administration for H. pylori inhibition are provided in an easy-to-understand format. Afterward, in vitro and in vivo studies of some promising bio-platforms including metal-based biomaterials, biopolymers, small-molecule saccharides, and vaccines for H. pylori inhibition are discussed in a holistic manner. EXPERT OPINION Functionalized or non-functionalized micro/nano biomaterials loaded with anti-H. pylori agents can show efficient bactericidal activity with no/slight negative influence on the host gastrointestinal microbiota. However, this claim needs to be substantiated with hard data such as assessment of the biopharmaceutical parameters of anti-H. pylori systems and the measurement of diversity/abundance of bacterial genera in the host gastric/gut microbiota before and after H. pylori eradication.
Collapse
Affiliation(s)
- Misagh Fathi Kisomi
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tara Shekari
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Amin
- Department of Drug and Food Control, Faculty of Pharmacy, and the Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Antoni Llopis-Lorente
- Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, Valencia, Spain
- CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III, Madrid, Spain
| | - Chenguang Liu
- College of Marine Life Science, Ocean University of China, Qingdao, P.R. China
| | - Ismaeil Haririan
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mazda Rad-Malekshahi
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Hossein Miri
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa
| | - Matthias G Wacker
- Department of Pharmacy, Faculty of Science, National University of Singapore, 4 Science Drive 2, Singapore 117545, Singapore
| |
Collapse
|
|
4
|
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.
Collapse
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
| | | |
Collapse
|
|
5
|
Wu S, Xu Y, Chen Z, Chen Y, Wei F, Xia C, Zhou Q, Li P, Gu Q. Lactiplantibacillus plantarum ZJ316 Reduces Helicobacter pylori Adhesion and Inflammation by Inhibiting the Expression of Adhesin and Urease Genes. Mol Nutr Food Res 2023; 67:e2300241. [PMID: 37485583 DOI: 10.1002/mnfr.202300241] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 06/02/2023] [Indexed: 07/25/2023]
Abstract
SCOPE The present study aims to investigate the anti-Helicobacter pylori (H. pylori) effects of Lactiplantibacillus plantarum ZJ316 (L. plantarum ZJ316) both in vitro and in vivo. METHODS AND RESULTS This study finds that L. plantarum ZJ316 effectively suppresses H. pylori adhesion in inhibition (Pre-ZJ316), competition (Co-ZJ316), and displacement (Post-ZJ316) assays, and Pre-ZJ316 displaying the most potent inhibitory effect with an impressive inhibition ratio of 70.14%. Upon anti-adhesion, L. plantarum ZJ316 significantly downregulates the expression of H. pylori virulence genes, including ureA, ureB, flaA, and sabA, with inhibition ratios of 46.83%, 24.02%, 21.42%, and 62.38% at 2 h, respectively. In addition, L. plantarum ZJ316 is observed to reduce the level of interleukin 8 (IL-8) and improve cell viability in infected AGS cells. Furthermore, in vivo studies show that supplementation with L. plantarum ZJ316 effectively hinders H. pylori colonization and significantly suppresses the infiltration of immune cells and IL-8 production with H. pylori infection, protecting host from inflammatory damage. CONCLUSION L. plantarum ZJ316 exhibits excellent adhesion inhibition on H. pylori, and may be used as a probiotic candidate in the prevention or adjuvant therapy of gastric disease caused by H. pylori.
Collapse
Affiliation(s)
- Shiying Wu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, 310018, China
| | - Yang Xu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, 310018, China
| | - Ziqi Chen
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, 310018, China
| | - Yongqiang Chen
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, 310018, China
| | - Fangtong Wei
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, 310018, China
| | - Chenlan Xia
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, 310018, China
| | - Qingqing Zhou
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, 310018, China
| | - Ping Li
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, 310018, China
| | - Qing Gu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, 310018, China
| |
Collapse
|
|
6
|
Yang H, Wang L, Zhang M, Hu B. The Role of Adhesion in Helicobacter pylori Persistent Colonization. Curr Microbiol 2023; 80:185. [PMID: 37071212 DOI: 10.1007/s00284-023-03264-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Accepted: 03/10/2023] [Indexed: 04/19/2023]
Abstract
Helicobacter pylori (H. pylori) has coevolved with its human host for more than 100 000 years. It can safely colonize around the epithelium of gastric glands via their specific microstructures and proteins. Unless patients receive eradication treatment, H. pylori infection is always lifelong. However, few studies have discussed the reasons. This review will focus on the adhesion of H. pylori from the oral cavity to gastric mucosa and summarize the possible binding and translocation characteristics. Adhesion is the first step for persistent colonization after the directional motility, and factors related to adhesion are necessary. Outer membrane proteins, such as the blood group antigen binding adhesin (BabA) and the sialic acid binding adhesin (SabA), play pivotal roles in binding to human mucins and cellular surfaces. And this may offer different perspectives on eradication.
Collapse
Affiliation(s)
- Hang Yang
- Department of Gastroenterology, West China Hospital, Sichuan University, No.37, Guo Xue Alley, Wu Hou District, Chengdu City, 610041, Sichuan Province, China
| | - Lixia Wang
- The Second Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Miao Zhang
- Department of Gastroenterology, West China Hospital, Sichuan University, No.37, Guo Xue Alley, Wu Hou District, Chengdu City, 610041, Sichuan Province, China
| | - Bing Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, No.37, Guo Xue Alley, Wu Hou District, Chengdu City, 610041, Sichuan Province, China.
| |
Collapse
|
|
7
|
O’Brien VP, Jackson LK, Frick JP, Rodriguez Martinez AE, Jones DS, Johnston CD, Salama NR. Helicobacter pylori Chronic Infection Selects for Effective Colonizers of Metaplastic Glands. mBio 2023; 14:e0311622. [PMID: 36598261 PMCID: PMC9973278 DOI: 10.1128/mbio.03116-22] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 12/05/2022] [Indexed: 01/05/2023] Open
Abstract
Chronic gastric infection with Helicobacter pylori can lead to progressive tissue changes that culminate in cancer, but how H. pylori adapts to the changing tissue environment during disease development is not fully understood. In a transgenic mouse gastric metaplasia model, we found that strains from unrelated individuals differed in their ability to infect the stomach, to colonize metaplastic glands, and to alter the expression of the metaplasia-associated protein TFF3. H. pylori isolates from different stages of disease from a single individual had differential ability to colonize healthy and metaplastic gastric glands. Exposure to the metaplastic environment selected for high gastric colonization by one of these strains. Complete genome sequencing revealed a unique alteration in the frequency of a variant allele of the putative adhesin sabB, arising from a recombination event with the related sialic acid binding adhesin (SabA) gene. Mutation of sabB in multiple H. pylori strain backgrounds strongly reduced adherence to both normal and metaplastic gastric tissue, and highly attenuated stomach colonization in mice. Thus, the changing gastric environment during disease development promotes bacterial adhesin gene variation associated with enhanced gastric colonization. IMPORTANCE Chronic infection with Helicobacter pylori is the primary risk factor for developing stomach cancer. As disease progresses H. pylori must adapt to a changing host tissue environment that includes induction of new cell fates in the cells that line the stomach. We tested representative H. pylori isolates collected from the same patient during early and later stages of disease in a mouse model where we can rapidly induce disease-associated tissue changes. Only the later-stage H. pylori strains could robustly colonize the diseased stomach environment. We also found that the ability to colonize the diseased stomach was associated with genetic variation in a putative cell surface adhesin gene called sabB. Additional experiments revealed that SabB promotes binding to stomach tissue and is critical for stomach colonization by the late-stage strains. Thus, H. pylori diversifies its genome during disease progression and these genomic changes highlight critical factors for bacterial persistence.
Collapse
Affiliation(s)
- V. P. O’Brien
- Human Biology Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | - L. K. Jackson
- Human Biology Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
- Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, Washington, USA
| | - J. P. Frick
- Human Biology Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
- Department of Microbiology, University of Washington, Seattle, Washington, USA
| | | | - D. S. Jones
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | - C. D. Johnston
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | - N. R. Salama
- Human Biology Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
- Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, Washington, USA
- Department of Microbiology, University of Washington, Seattle, Washington, USA
| |
Collapse
|
|
8
|
Yang H, Mou Y, Hu B. Discussion on the common controversies of Helicobacter pylori infection. Helicobacter 2023; 28:e12938. [PMID: 36436202 DOI: 10.1111/hel.12938] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 11/02/2022] [Accepted: 11/03/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Helicobacter pylori ( H. pylori ) can persistently colonize on the gastric mucosa after infection and cause gastritis, atrophy, metaplasia, and even gastric cancer (GC). METHODS Therefore, the detection and eradication of H. pylori are the prerequisite. RESULTS Clinically, there are some controversial issues, such as why H. pylori infection is persistent, why it translocases along with the lesser curvature of the stomach, why there is oxyntic antralization, what the immunological characteristic of gastric chronic inflammation caused by H. pylori is, whether H. pylori infection is associated with extra-gastric diseases, whether chronic atrophic gastritis (CAG) is reversible, and what the potential problems are after H. pylori eradication. What are the possible answers? CONCLUSION In the review, we will discuss these issues from the attachment to eradication in detail.
Collapse
Affiliation(s)
- Hang Yang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Yi Mou
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Bing Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| |
Collapse
|
|
9
|
Shokri Shirvani J, Salehi M, Rezaei Majd A, Sadeghi F, Ferdosi-Shahandashti E, Khafri S, Rajabnia M. Expression Assessment of the Helicobacter pyloribabA and sabA Genes in Patients with Peptic Ulcer, Duodenal Ulcer and Gastric Cancer. INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE 2023; 12:211-219. [PMID: 38313370 PMCID: PMC10837913 DOI: 10.22088/ijmcm.bums.12.2.211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 10/04/2023] [Accepted: 11/25/2023] [Indexed: 02/06/2024]
Abstract
Helicobacter pylori as a common gastrointestinal (GI) pathogen must possess certain virulence characteristics to colonize the stomach, evade host immune responses, and subsequently induce GI diseases. This research aimed to investigate the expression level of two important genes, the sialic acid-binding adherence (SabA) and the blood group antigen-binding adhesion (BabA) in H. pylori strains isolated from adult patients living in the northern part of Iran, and their association with peptic ulcer disease (PUD) and gastric cancer (GC). This cross-sectional study was carried out on adult patients referring to the GI clinic of the hospitals affiliated to Babol University of Medical Sciences, Iran. New cases diagnosed with gastritis, peptic ulcer or gastric cancer were included. Endoscopic-guided gastric biopsies were examined and H. pylori positive colonies were analyzed to determine the expression of babA and sabA genes, utilizing specific primers and the SYBR Green dye. Among 175 patients with mean age of 51.6±15.6 years, 101 (57.7%) of the individuals tested positive for H. pylori infection. Statistical analysis revealed a significant correlation between sabA (P=0.003) and babA (P=0.002) gene expression and development of PUD and GC. Smoking (P=0.052), gender (P=0.004) and positive babA gene expression (P=0.009) had the greatest association with occurrence of PUD or GC in H. pylori positive patients. In summary, the presence of the sabA gene in people infected with H. pylori increased the risk of GC compared to gastritis, while, the presence of the babA gene was significantly increased in gastric ulcer patients. Considering the diversity of H. pylori isolates and the varying results observed in different geographical regions, further comprehensive studies are required to evaluate the function of these genes in H. pylori pathogenesis and their relationship with clinical outcomes.
Collapse
Affiliation(s)
- Javad Shokri Shirvani
- Biomedical and Microbial Advanced Technologies Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Maryam Salehi
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | | | - Farzin Sadeghi
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Elaheh Ferdosi-Shahandashti
- Biomedical and Microbial Advanced Technologies Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Soraya Khafri
- Infertility and Reproductive Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Mehdi Rajabnia
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| |
Collapse
|
|
10
|
Yamaoka Y, Saruuljavkhlan B, Alfaray RI, Linz B. Pathogenomics of Helicobacter pylori. Curr Top Microbiol Immunol 2023; 444:117-155. [PMID: 38231217 DOI: 10.1007/978-3-031-47331-9_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
The human stomach bacterium Helicobacter pylori, the causative agent of gastritis, ulcers and adenocarcinoma, possesses very high genetic diversity. H. pylori has been associated with anatomically modern humans since their origins over 100,000 years ago and has co-evolved with its human host ever since. Predominantly intrafamilial and local transmission, along with genetic isolation, genetic drift, and selection have facilitated the development of distinct bacterial populations that are characteristic for large geographical areas. H. pylori utilizes a large arsenal of virulence and colonization factors to mediate the interaction with its host. Those include various adhesins, the vacuolating cytotoxin VacA, urease, serine protease HtrA, the cytotoxin-associated genes pathogenicity island (cagPAI)-encoded type-IV secretion system and its effector protein CagA, all of which contribute to disease development. While many pathogenicity-related factors are present in all strains, some belong to the auxiliary genome and are associated with specific phylogeographic populations. H. pylori is naturally competent for DNA uptake and recombination, and its genome evolution is driven by extraordinarily high recombination and mutation rates that are by far exceeding those in other bacteria. Comparative genome analyses revealed that adaptation of H. pylori to individual hosts is associated with strong selection for particular protein variants that facilitate immune evasion, especially in surface-exposed and in secreted virulence factors. Recent studies identified single-nucleotide polymorphisms (SNPs) in H. pylori that are associated with the development of severe gastric disease, including gastric cancer. Here, we review the current knowledge about the pathogenomics of H. pylori.
Collapse
Affiliation(s)
- Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1, Idaigaoka, Hasama-machi, Yufu Oita, 879-5593, Japan
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Batsaikhan Saruuljavkhlan
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1, Idaigaoka, Hasama-machi, Yufu Oita, 879-5593, Japan
| | - Ricky Indra Alfaray
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1, Idaigaoka, Hasama-machi, Yufu Oita, 879-5593, Japan
- Helicobacter pylori and Microbiota Study Group, Universitas Airlangga, Surabaya, 60286, East Java, Indonesia
| | - Bodo Linz
- Division of Microbiology, Department Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058, Erlangen, Germany.
| |
Collapse
|
|
11
|
Kim N, Park YH. Atrophic Gastritis and Intestinal Metaplasia. HELICOBACTER PYLORI 2023:229-251. [DOI: 10.1007/978-981-97-0013-4_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
12
|
Somiah T, Gebremariam HG, Zuo F, Smirnova K, Jonsson AB. Lactate causes downregulation of Helicobacter pylori adhesin genes sabA and labA while dampening the production of proinflammatory cytokines. Sci Rep 2022; 12:20064. [PMID: 36414643 PMCID: PMC9681763 DOI: 10.1038/s41598-022-24311-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 11/14/2022] [Indexed: 11/24/2022] Open
Abstract
Chronic inflammation induced by Helicobacter pylori is strongly associated with gastric cancer development, which is influenced by both bacterial virulence and host genetics. The sialic acid-binding adhesin SabA and the MUC5AC-binding adhesin LabA are important H. pylori virulence factors that facilitate adhesion of the bacterium, which is a crucial step in colonization. Lactate utilization has been reported to play a key role in the pathogenicity of different bacterial species. However, this is poorly understood in H. pylori. In this study, we investigated the effect of lactate on H. pylori adhesin gene expression and the regulation of host inflammatory cytokines. We show that the bacterial adhesins SabA and LabA were downregulated at the transcriptional level during incubation of H. pylori with lactate. Downregulation of sabA required the involvement of the two-component system ArsRS, while labA was regulated via the CheA/CheY system, indicating differences in the regulation of these genes in response to lactate. The levels of the proinflammatory cytokines TNF and IL-6 in H. pylori-stimulated macrophages were reduced when lactate was present. Interestingly, glucose did not prevent the secretion of these cytokines. Taken together, our data suggest that lactate affects H. pylori adhesin gene expression and the host response upon infection.
Collapse
Affiliation(s)
- Tanvi Somiah
- grid.10548.380000 0004 1936 9377Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrheniusväg 20C, 10691 Stockholm, Sweden
| | - Hanna G. Gebremariam
- grid.10548.380000 0004 1936 9377Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrheniusväg 20C, 10691 Stockholm, Sweden
| | - Fanglei Zuo
- grid.10548.380000 0004 1936 9377Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrheniusväg 20C, 10691 Stockholm, Sweden
| | - Ksenija Smirnova
- grid.10548.380000 0004 1936 9377Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrheniusväg 20C, 10691 Stockholm, Sweden
| | - Ann-Beth Jonsson
- grid.10548.380000 0004 1936 9377Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrheniusväg 20C, 10691 Stockholm, Sweden
| |
Collapse
|
|
13
|
Ansari S, Yamaoka Y. Helicobacter pylori Infection, Its Laboratory Diagnosis, and Antimicrobial Resistance: a Perspective of Clinical Relevance. Clin Microbiol Rev 2022; 35:e0025821. [PMID: 35404105 PMCID: PMC9491184 DOI: 10.1128/cmr.00258-21] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Despite the recent decrease in overall prevalence of Helicobacter pylori infection, morbidity and mortality rates associated with gastric cancer remain high. The antimicrobial resistance developments and treatment failure are fueling the global burden of H. pylori-associated gastric complications. Accurate diagnosis remains the opening move for treatment and eradication of infections caused by microorganisms. Although several reports have been published on diagnostic approaches for H. pylori infection, most lack the data regarding diagnosis from a clinical perspective. Therefore, we provide an intensive, comprehensive, and updated description of the currently available diagnostic methods that can help clinicians, infection diagnosis professionals, and H. pylori researchers working on infection epidemiology to broaden their understanding and to select appropriate diagnostic methods. We also emphasize appropriate diagnostic approaches based on clinical settings (either clinical diagnosis or mass screening), patient factors (either age or other predisposing factors), and clinical factors (either upper gastrointestinal bleeding or partial gastrectomy) and appropriate methods to be considered for evaluating eradication efficacy. Furthermore, to cope with the increasing trend of antimicrobial resistance, a better understanding of its emergence and current diagnostic approaches for resistance detection remain inevitable.
Collapse
Affiliation(s)
- Shamshul Ansari
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu City, Oita, Japan
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu City, Oita, Japan
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas, USA
- Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
| |
Collapse
|
|
14
|
Vital JS, Tanoeiro L, Lopes-Oliveira R, Vale FF. Biomarker Characterization and Prediction of Virulence and Antibiotic Resistance from Helicobacter pylori Next Generation Sequencing Data. Biomolecules 2022; 12:691. [PMID: 35625618 PMCID: PMC9138241 DOI: 10.3390/biom12050691] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 05/02/2022] [Accepted: 05/07/2022] [Indexed: 02/06/2023] Open
Abstract
The Gram-negative bacterium Helicobacter pylori colonizes c.a. 50% of human stomachs worldwide and is the major risk factor for gastric adenocarcinoma. Its high genetic variability makes it difficult to identify biomarkers of early stages of infection that can reliably predict its outcome. Moreover, the increasing antibiotic resistance found in H. pylori defies therapy, constituting a major human health problem. Here, we review H. pylori virulence factors and genes involved in antibiotic resistance, as well as the technologies currently used for their detection. Furthermore, we show that next generation sequencing may lead to faster characterization of virulence factors and prediction of the antibiotic resistance profile, thus contributing to personalized treatment and management of H. pylori-associated infections. With this new approach, more and permanent data will be generated at a lower cost, opening the future to new applications for H. pylori biomarker identification and antibiotic resistance prediction.
Collapse
Affiliation(s)
- Joana S. Vital
- Pathogen Genome Bioinformatics and Computational Biology, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal; (J.S.V.); (L.T.); (R.L.-O.)
| | - Luís Tanoeiro
- Pathogen Genome Bioinformatics and Computational Biology, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal; (J.S.V.); (L.T.); (R.L.-O.)
| | - Ricardo Lopes-Oliveira
- Pathogen Genome Bioinformatics and Computational Biology, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal; (J.S.V.); (L.T.); (R.L.-O.)
| | - Filipa F. Vale
- Pathogen Genome Bioinformatics and Computational Biology, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal; (J.S.V.); (L.T.); (R.L.-O.)
| |
Collapse
|
|
15
|
Kim A, Lai J, Merrell DS, Kim JH, Su H, Cha JH. Geographic diversity in Helicobacter pylori oipA genotype between Korean and United States isolates. J Microbiol 2021; 59:1125-1132. [PMID: 34718962 DOI: 10.1007/s12275-021-1450-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/15/2021] [Accepted: 09/23/2021] [Indexed: 12/30/2022]
Abstract
Helicobacter pylori outer membrane inflammatory protein A (OipA) was originally named for its role in inducing inflammation in the host, as evidenced by high mucosal IL-8 levels. Expression of OipA is regulated by phase variation of a CT dinucleotide-repeat located in the 5' region of the gene. However, little is known about OipA geographic diversity across isolates. To address this gap, we conducted a large-scale molecular epidemiologic analysis using H. pylori clinical isolates obtained from two geographically distinct populations: Korea and the United States (US). Most Korean isolates (98.7%) possessed two copies of oipA located at two specific loci (A and B) while all US isolates contained only one copy of oipA at locus A. Furthermore, most Korean oipA (94.8%) possessed three or less CT repeats while most US oipA (96.6%) contained five or more CT repeats. Among the two copies, all Korean H. pylori possessed at least one oipA 'on' phase variant while the single copy of oipA in US isolates showed 56.2% 'on' and 43.8% 'off.' Thus, host differences seem to have driven geographic diversification of H. pylori across these populations such that OipA expression in US isolates is still regulated by phase variation with 5 or more CT repeats, while Korean isolates always express OipA; duplication of the oipA combined with a reduction of CT repeats to three or less ensures continued expression. En masse, these findings suggest that diversity in the oipA gene copy number, CT repeats, and phase variation among H. pylori from different populations may confer a benefit in adaptation to particular host populations.
Collapse
Affiliation(s)
- Aeryun Kim
- Department of Oral Biology, Oral Science Research Center, Department of Applied Life Science, The Graduate School, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, 03722, Republic of Korea.,Department of Dental Hygiene, Gangdong University, Eumseong, 27600, Republic of Korea
| | - Jing Lai
- Department of Oral Biology, Oral Science Research Center, Department of Applied Life Science, The Graduate School, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, 03722, Republic of Korea
| | - D Scott Merrell
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, 20814, USA
| | - Ji-Hye Kim
- Department of Dental Hygiene, Baekseok University, Cheonan, 31065, Republic of Korea.
| | - Hanfu Su
- Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510182, P. R. China.
| | - Jeong-Heon Cha
- Department of Oral Biology, Oral Science Research Center, Department of Applied Life Science, The Graduate School, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, 03722, Republic of Korea. .,Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510182, P. R. China.
| |
Collapse
|
|
16
|
Hedayati MA, Ahmadi S, Servatyari K, Sheikhesmaeili F. PREX2 gene's expression in gastric antral epithelial cells of patients with H. pylori infection. ARQUIVOS DE GASTROENTEROLOGIA 2021; 58:353-358. [PMID: 34705970 DOI: 10.1590/s0004-2803.202100000-59] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 03/03/2021] [Indexed: 11/21/2022]
Abstract
BACKGROUND The Prex2 protein is a member of the Rac family proteins that belongs to small G proteins with a critical role in cell migration, cell proliferation, and apoptosis through its effects on PI3K cell signaling pathway and phosphatase activity of PTEN protein. The effect of PREX2 gene expression has been shown in some cancer cells. A survey of PREX2 gene expression in gastric antral epithelial cells of gastric cancer patients with Helicobacter pylori various genotypes infection can conduct to better understanding H. pylori infection's carcinogenesis. METHODS In a case-control study, PREX2 gene expression was evaluated in gastric antral biopsy samples on four groups of patients referred to Sanandaj hospitals, including gastritis with (n=23) and without (n=27) H. pylori infection and gastric cancer with (n=21) and without (n=32) H. pylori infection. Each gastric biopsy sample's total RNA was extracted and cDNA synthesized by using Kits (Takara Company). The PREX2 gene expression was measured using the relative quantitative real-time RT-PCR method and ΔΔCt formula. RESULTS The PREX2 gene expression increased in gastric antral biopsy samples of gastritis and gastric cancer patients with H. pylori infection (case groups) than patients without H. pylori infection (control groups) 2.38 and 2.27 times, respectively. The patients with H. pylori vacA s1m1 and sabB genotypes infection showed a significant increase of PREX2 gene expression in gastric cancer antral epithelial cells. CONCLUSION H. pylori vacA s1m1 and sabB genotypes have the positive correlations with PREX2 gene expression in gastric antral epithelial cells of gastritis and gastric cancer patients.
Collapse
Affiliation(s)
- Manouchehr Ahmadi Hedayati
- Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.,Department of Microbiology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Sanaz Ahmadi
- Department of Microbiology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.,Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Karo Servatyari
- Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Farshad Sheikhesmaeili
- Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| |
Collapse
|
|
17
|
Kim HW, Woo HJ, Yang JY, Kim JB, Kim SH. Hesperetin Inhibits Expression of Virulence Factors and Growth of Helicobacter pylori. Int J Mol Sci 2021; 22:ijms221810035. [PMID: 34576198 PMCID: PMC8472136 DOI: 10.3390/ijms221810035] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 09/09/2021] [Accepted: 09/13/2021] [Indexed: 12/22/2022] Open
Abstract
Helicobacter pylori (H. pylori) is a bacterium known to infect the human stomach. It can cause various gastrointestinal diseases including gastritis and gastric cancer. Hesperetin is a major flavanone component contained in citrus fruits. It has been reported to possess antibacterial, antioxidant, and anticancer effects. However, the antibacterial mechanism of hesperetin against H. pylori has not been reported yet. Therefore, the objective of this study was to determine the inhibitory effects of hesperetin on H. pylori growth and its inhibitory mechanisms. The results of this study showed that hesperetin inhibits the growth of H. pylori reference strains and clinical isolates. Hesperetin inhibits the expression of genes in replication (dnaE, dnaN, dnaQ, and holB) and transcription (rpoA, rpoB, rpoD, and rpoN) machineries of H. pylori. Hesperetin also inhibits the expression of genes related to H. pylori motility (flhA, flaA, and flgE) and adhesion (sabA, alpA, alpB, hpaA, and hopZ). It also inhibits the expression of urease. Hespereti n downregulates major virulence factors such as cytotoxin-associated antigen A (CagA) and vacuolating cytotoxin A (VacA) and decreases the translocation of CagA and VacA proteins into gastric adenocarcinoma (AGS) cells. These results might be due to decreased expression of the type IV secretion system (T4SS) and type V secretion system (T5SS) involved in translocation of CagA and VacA, respectively. The results of this study indicate that hesperetin has antibacterial effects against H. pylori. Thus, hesperetin might be an effective natural product for the eradication of H. pylori.
Collapse
Affiliation(s)
- Hyun Woo Kim
- Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 26493, Korea; (H.W.K.); (J.-B.K.)
| | - Hyun Jun Woo
- Department of Clinical Laboratory Science, Semyung University, Jecheon 27136, Korea;
| | - Ji Yeong Yang
- Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA), Wanju 55365, Korea;
| | - Jong-Bae Kim
- Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 26493, Korea; (H.W.K.); (J.-B.K.)
| | - Sa-Hyun Kim
- Department of Clinical Laboratory Science, Semyung University, Jecheon 27136, Korea;
- Correspondence:
| |
Collapse
|
|
18
|
Prakosa AW, Miftahussurur M, Juniastuti J, Waskito LA, Doohan D, Fauzia KA, Rezkitha YAA, Sugihartono T, Syam AF, Uchida T, Yamaoka Y. Characterization of Helicobacter pylori tlyA and Its Association with Bacterial Density. Dig Dis 2021; 40:417-426. [PMID: 34515099 DOI: 10.1159/000518538] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 07/19/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND In the recent studies, a less virulent Helicobacter pylori variant could still colonize the human stomach and induce gastric inflammation, suggesting the involvement of other virulence factors, such as TlyA hemolysin. Nevertheless, the association of TlyA in the pathogenesis of H. pylori infection remains unclear. We investigated the tlyA profile and determined its relationship with gastritis severity. METHODS An observational study was conducted using DNA stocks and secondary data from previous studies. The tlyA variant was examined by NGS and confirmed with polymerase chain reaction. Gastritis severity was categorized by the Updated Sydney System. The relationship between a variant of tlyA and gastritis severity was determined, in which discrete variables were tested using the χ2 test or Fisher exact test. RESULTS Two H. pylori tlyA variants were observed and characterized as tlyA1 and tlyA2. We noted a unique variant in the amino acid sequence 32-35 that is exclusively detected among H. pylori isolated from the Papua island. In addition, we observed that the tlyA variant had a significant association with the H. pylori density in the antral (p = 0.002). Histological analyses revealed that TlyA1 was associated with higher H. pylori density than TlyA2. However, we did not observe any significant association of tlyA with the infiltration of inflammation cells. CONCLUSIONS We observed 2 tlyA variants (tlyA1 and tlyA2). A significant association of tlyA with bacterial density suggested that tlyA plays a more significant role in the colonization process than its influence on the severity of inflammation in gastric mucosa.
Collapse
Affiliation(s)
- Adi Wasis Prakosa
- Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.,Universitas Airlangga Teaching Hospital, Surabaya, Indonesia
| | - Muhammad Miftahussurur
- Gastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga-Dr. Soetomo Teaching Hospital, Surabaya, Indonesia.,Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.,Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan
| | | | - Langgeng Agung Waskito
- Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.,Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan
| | - Dalla Doohan
- Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.,Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kartika Afrida Fauzia
- Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.,Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan
| | - Yudith Annisa Ayu Rezkitha
- Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.,Faculty of Medicine, University of Muhammadiyah Surabaya, Surabaya, Indonesia
| | - Titong Sugihartono
- Gastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga-Dr. Soetomo Teaching Hospital, Surabaya, Indonesia
| | - Ari Fahrial Syam
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Tomohisa Uchida
- Department of Molecular Pathology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Yoshio Yamaoka
- Gastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga-Dr. Soetomo Teaching Hospital, Surabaya, Indonesia.,Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan
| |
Collapse
|
|
19
|
Padda J, Khalid K, Cooper AC, Jean-Charles G. Association Between Helicobacter pylori and Gastric Carcinoma. Cureus 2021; 13:e15165. [PMID: 34168929 PMCID: PMC8216031 DOI: 10.7759/cureus.15165] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/21/2021] [Indexed: 12/24/2022] Open
Abstract
Gastric carcinoma is the third leading cause of cancer mortality worldwide. In 2018, the incidence of gastric carcinoma worldwide was over 1,000,000 new cases, with approximately 783,000 deaths. The rate of new cases is noticeably increased in Eastern Asia. Helicobacter pylori is responsible for the increased incidence of gastric cancer. In the year 2015, H. pylori had an approximate prevalence of 4.4 billion positive cases worldwide, with the most positive cases found within the region of Africa, Latin America and the Caribbean, and of Asia. H. pylori is known to have multiple strains which allow it to survive in the host cell epithelium chronically. Research has shown many factors which play a significant role in developing infection and thereafter its progression to gastric carcinoma. After H. pylori colonizes the gastric mucosa, its effects can be potentiated by virulence factors, host factors, and environmental factors. H. pylori contains virulence factors that aid in the adhesion, translocation, inflammation, and infectivity of the host gastric epithelium. It alters the functions of the host immune response and cytokines, utilizing these factors to invade and persist in the gastric epithelium for a long period of time. The human body will identify H. pylori to be foreign and will exacerbate an inflammatory response in an effort to eradicate the bacterium. Consequently, this will cause H. pylori to induce a serious infection which may progress to cancer. In this review, we will discuss the various factors involved in the infectious process of H. pylori and how they help the infection progress to gastric carcinoma. This will allow us to better understand and modulate treatments to effectively eradicate this bacterium before it triggers the body into developing cancer.
Collapse
Affiliation(s)
| | | | | | - Gutteridge Jean-Charles
- Internal Medicine, Advent Health and Orlando Health Hospital/JC Medical Center, Orlando, USA
| |
Collapse
|
|
20
|
Fan R, Han X, Gong Y, He L, Xue Z, Yang Y, Sun L, Fan D, You Y, Meng F, Yan X, Zhang M, Zhang J. Alterations of Fucosyltransferase Genes and Fucosylated Glycans in Gastric Epithelial Cells Infected with Helicobacter pylori. Pathogens 2021; 10:pathogens10020168. [PMID: 33557187 PMCID: PMC7913934 DOI: 10.3390/pathogens10020168] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 01/31/2021] [Accepted: 02/01/2021] [Indexed: 12/20/2022] Open
Abstract
Helicobacter pylori (H. pylori) adhesion to human gastric epithelial cells is closely linked with fucosylated glycans. Therefore, investigation of fucosylation in the interaction of gastric epithelial cells with H. pylori is critical. In this study we used lectin microarrays to detect the expression of fucosylated glycans in gastric epithelial cells (GES-1) infected with H. pylori strains isolated from patients with different diseases including chronic gastritis, duodenal ulcers, and gastric cancer (each containing two strains) at 4 h. In addition, we investigated the time-course expression of fucosyltransferase (FUT) 1–6 genes in GES-1 cells stimulated with H. pylori strains at 0.5–8 h. At 4 h post-infection, Lotus, AAA, BC2LCN, PA-IIL, CNL and ACG lectins had increased signals in H. pylori-infected GES-1 cells compared to uninfected cells. Higher expression of FUT1 and FUT2 was detected in all H. pylori-infected GES-1 cells within 2 h, regardless of the H. pylori strain. In particular, the expression of FUT2 was higher in H. pylori-infected GES-1 cells with a higher fold change in levels of BC2LCN lectin specific to α1-2 linked fucose (Fuc) at 4 h. The results suggest that the high levels of α1, 2-linked Fuc synthesized by FUT1/2, might play a role in the preliminary stage of H. pylori infection. This provides us with pivotal information to understand the adhesion of H. pylori to human gastric epithelial cells.
Collapse
|
|
21
|
Banga Ndzouboukou JL, Lei Q, Ullah N, Zhang Y, Hao L, Fan X. Helicobacter pylori adhesins: HpaA a potential antigen in experimental vaccines for H. pylori. Helicobacter 2021; 26:e12758. [PMID: 33259676 DOI: 10.1111/hel.12758] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 08/14/2020] [Accepted: 09/01/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND Helicobacter pylori is a gram-negative bacterium involved in many gastric pathologies such as ulcers and cancers. Although the treatment for this infection has existed for several years, the development of a vaccine is nevertheless necessary to reduce the severe forms of the disease. For more than three decades, many advances have been made particularly in the understanding of virulence factors as well as the pathogenesis of gastric diseases caused by H. pylori. Among these key virulence factors, specific antigens have been identified: Urease, Vacuolating cytotoxin A (VacA), Cytotoxin-associated gene A (CagA), Blood group antigen-binding adhesin (BabA), H. pylori adhesin A (HpaA), and others. OBJECTIVES This review will focus on H. pylori adhesins, in particular, on HpaA and on the current knowledge of H. pylori vaccines. METHODS All of the information included in this review was retrieved from published studies on H. pylori adhesins in H. pylori infections. RESULTS These proteins, used in their native or recombinant forms, induce protection against H. pylori in experimental animal models. CONCLUSION H. pylori adhesins are known to be promising candidate vaccines against H. pylori. Future research should be carried out on adhesins, in particular, on HpaA.
Collapse
Affiliation(s)
- Jo-Lewis Banga Ndzouboukou
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qing Lei
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Nadeem Ullah
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yandi Zhang
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ling Hao
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xionglin Fan
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| |
Collapse
|
|
22
|
FitzGerald R, Sinha C, Yadegar A, Smith SM. Helicobacter pylori Virulence Factor Genotyping. Methods Mol Biol 2021; 2283:93-106. [PMID: 33765313 DOI: 10.1007/978-1-0716-1302-3_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Helicobacter pylori (H. pylori) infection causes chronic gastritis, peptic ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma. Bacterial, host, and environmental factors influence the progression of disease from superficial gastritis to cancer. H. pylori is genetically diverse, and expression of its specific virulence factors has been linked to increased risk of more severe pathologies. Described in this chapter is a protocol for detecting important H. pylori virulence factors by firstly extracting DNA from culture material or stomach tissue biopsies, followed by PCR amplification and agarose gel electrophoresis.
Collapse
Affiliation(s)
| | - Chavi Sinha
- School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sinéad M Smith
- Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin 2, Ireland.
| |
Collapse
|
|
23
|
Baj J, Forma A, Sitarz M, Portincasa P, Garruti G, Krasowska D, Maciejewski R. Helicobacter pylori Virulence Factors-Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment. Cells 2020; 10:27. [PMID: 33375694 PMCID: PMC7824444 DOI: 10.3390/cells10010027] [Citation(s) in RCA: 201] [Impact Index Per Article: 40.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/18/2020] [Accepted: 12/22/2020] [Indexed: 12/11/2022] Open
Abstract
Gastric cancer constitutes one of the most prevalent malignancies in both sexes; it is currently the fourth major cause of cancer-related deaths worldwide. The pathogenesis of gastric cancer is associated with the interaction between genetic and environmental factors, among which infection by Helicobacter pylori (H. pylori) is of major importance. The invasion, survival, colonization, and stimulation of further inflammation within the gastric mucosa are possible due to several evasive mechanisms induced by the virulence factors that are expressed by the bacterium. The knowledge concerning the mechanisms of H. pylori pathogenicity is crucial to ameliorate eradication strategies preventing the possible induction of carcinogenesis. This review highlights the current state of knowledge and the most recent findings regarding H. pylori virulence factors and their relationship with gastric premalignant lesions and further carcinogenesis.
Collapse
Affiliation(s)
- Jacek Baj
- Department of Anatomy, Medical University of Lublin, 20-400 Lublin, Poland;
| | - Alicja Forma
- Chair and Department of Forensic Medicine, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Monika Sitarz
- Department of Conservative Dentistry with Endodontics, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Piero Portincasa
- Clinica Medica “Augusto Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy;
| | - Gabriella Garruti
- Section of Endocrinology, Department of Emergency and Organ Transplantations, University of Bari “Aldo Moro” Medical School, Piazza G. Cesare 11, 70124 Bari, Italy;
| | - Danuta Krasowska
- Department of Dermatology, Venerology and Paediatric Dermatology of Medical University of Lublin, 20-081 Lublin, Poland;
| | | |
Collapse
|
|
24
|
Xu C, Soyfoo DM, Wu Y, Xu S. Virulence of Helicobacter pylori outer membrane proteins: an updated review. Eur J Clin Microbiol Infect Dis 2020; 39:1821-1830. [PMID: 32557327 PMCID: PMC7299134 DOI: 10.1007/s10096-020-03948-y] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 06/09/2020] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori (H. pylori) infection is associated with some gastric diseases, such as gastritis, peptic ulcer, and gastric cancer. CagA and VacA are known virulence factors of H. pylori, which play a vital role in severe clinical outcomes. Additionally, the expression of outer membrane proteins (OMPs) helps H. pylori attach to gastric epithelial cells at the primary stage and increases the virulence of H. pylori. In this review, we have summarized the paralogs of H. pylori OMPs, their genomic loci, and the different receptors of OMPs identified so far. We focused on five OMPs, BabA (HopS), SabA (HopP), OipA (HopH), HopQ, and HopZ, and one family of OMPs: Hom. We highlight the coexpression of OMPs with other virulence factors and their relationship with clinical outcomes. In conclusion, OMPs are closely related to the pathogenic processes of adhesion, colonization, persistent infection, and severe clinical consequences. They are potential targets for the prevention and treatment of H. pylori–related diseases.
Collapse
Affiliation(s)
- Chenjing Xu
- Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | | | - Yao Wu
- Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Shunfu Xu
- Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China. .,Jiangsu Province Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
| |
Collapse
|
|
25
|
Keikha M, Eslami M, Yousefi B, Ghasemian A, Karbalaei M. Potential antigen candidates for subunit vaccine development against Helicobacter pylori infection. J Cell Physiol 2019; 234:21460-21470. [PMID: 31188484 DOI: 10.1002/jcp.28870] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 05/08/2019] [Accepted: 05/09/2019] [Indexed: 02/05/2023]
Abstract
Helicobacter pylori (H. pylori) is a resident bacterium in the stomach that accounts for 75% cases of gastric cancer. In this review, we comprehensively studied published papers on H. pylori vaccines using Google Scholar and NCBI databases to gather information about vaccines against H. pylori. Considering the pivotal roles of the enzyme urease (in production of NH3 and neutralization of the acidic medium of the stomach), cytotoxin-associated gene A, and vacuolating cytotoxin A proteins in H. pylori infection, they could be the best candidates for the construction of recombinant vaccines. The outer membrane porins (Hop), blood group antigen-binding adhesin (BabA), sialic acid-binding adhesin (SabA), and outer inflammatory protein A, play significant roles in binding of bacterium to human gastric tissues, and because binding is the first step in bacterial fixation and colonization, these antigens also can be considered as suitable candidates for designing vaccines. Likely, other significant bacterial antigens, such as NapA (chemotactic factor for recruitment of human neutrophils and monocytes to the site of infection), duodenal ulcer promoting protein A (to promote duodenal ulcer), and Hsp60 (as a molecular chaperon for activation of urease enzyme), can be used in the construction of subunit vaccines. New vaccines in use currently, such as DNA vaccines and subunit vaccines, can efficiently replace the dead and attenuated vaccines. Nonetheless, the results show that urease enzyme is most used compared with bacterial components in the designing and construction of recombinant vaccines. The BabA and SabA antigens belong to the outer membrane porins family in H. pylori and are required for binding and fixation of the bacterium to the human gastric tissues.
Collapse
Affiliation(s)
- Masoud Keikha
- Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Eslami
- Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | - Bahman Yousefi
- Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
| | - Abdolmajid Ghasemian
- Department of Biology, Tehran Central Branch, Islamic Azad University, Tehran, Iran
| | - Mohsen Karbalaei
- Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Microbiology and Virology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran
| |
Collapse
|
|
26
|
Šterbenc A, Jarc E, Poljak M, Homan M. Helicobacter pylori virulence genes. World J Gastroenterol 2019; 25:4870-4884. [PMID: 31543679 PMCID: PMC6737321 DOI: 10.3748/wjg.v25.i33.4870] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 07/29/2019] [Accepted: 08/07/2019] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is one of the most important human pathogens, infecting approximately half of the global population. Despite its high prevalence, only a subset of H. pylori infected individuals develop serious gastroduodenal pathology. The pathogenesis of H. pylori infection and disease outcome is thus thought to be mediated by an intricate interplay between host, environmental and bacterial virulence factors. H. pylori has adapted to the harsh milieu of the human stomach through possession of various virulence genes that enable survival of the bacteria in the acidic environment, movement towards the gastric epithelium, and attachment to gastric epithelial cells. These virulence factors enable successful colonization of the gastric mucosa and sustain persistent H. pylori infection, causing chronic inflammation and tissue damage, which may eventually lead to the development of peptic ulcers and gastric cancer. Numerous studies have focused on the prevalence and role of putative H. pylori virulence genes in disease pathogenesis. While several virulence factors with various functions have been identified, disease associations appear to be less evident, especially among different study populations. This review presents key findings on the most important H. pylori virulence genes, including several bacterial adhesins and toxins, in children and adults, and focuses on their prevalence, clinical significance and potential relationships.
Collapse
Affiliation(s)
- Anja Šterbenc
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Erika Jarc
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Mario Poljak
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Matjaž Homan
- Department of Gastroenterology, Hepatology and Nutrition, University Children’s Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| |
Collapse
|
|
27
|
Pozdeev ОК, Pozdeeva АО, Valeeva YV, Gulyaev PE. MECHANISMS OF INTERRACTION OF HELICOBACTER PYLORI WITH EPITHELIUM OF GASTRIC MUCOSA. I. PATHOGENIC FACTORS PROMOTING SUCCESSFUL COLONIZATION. RUSSIAN JOURNAL OF INFECTION AND IMMUNITY 2018; 8:273-283. [DOI: 10.15789/2220-7619-2018-3-273-283] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
H. pylori is a Gram-negative, crimp and motile bacterium that colonizes the hostile microniche of the human stomach roughly one half of the human population. Then persists for the host’s entire life, but only causes overt gastric disease in a subset of infected hosts. To the reasons contributing to the development of diseases, usually include: concomitant infections of the gastrointestinal tract, improper sterilization of medical instruments, usually endoscopes, nonobservance of personal hygiene rules, prolonged contact with infected or carriers, including family members and a number of other factors. Clinically, H. pylori plays a causative role in the development of a wide spectrum of diseases including chronic active gastritis, peptic and duodenal ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Due to the global distribution of H. pylori, we are able to conclude that smart strategies are contributing to adaptation of the bacterium in an aggressive environment of a stomach and lifelong permanent circulation in its host. Thirty-four years after the discovery of this bacterium, there are still many unanswered questions. For example, which strategies help the bacterium to survive in this inhospitable conditions? Understanding the mechanisms governing H. pylori persistence will improve identification of the increased risk of different gastric diseases in persons infected with this bacterium. A well-defined and long-term equilibrium between the human host and H. pylori allows bacterial persistence in the gastric microniche; although this coexistence leads to a high risk of severe diseases the diseases which are listed above. In this review, we discuss the pathogenesis of this bacterium and the mechanisms it uses to promote persistent colonization of the gastric mucosa, with a focus on recent insights into the role of some virulence factors like urease, LPS, outer membrane proteins, cytotoxins, factors, promoting invasion. Information on the mechanisms related to H. pylori persistence can also provide the direction for future research concerning effective therapy and management of gastroduodenal disorders. The topics presented in the current review are important for elucidating the strategies used by H. pylori to help the bacterium persist in relation to the many unfavorable features of living in the gastric microniche.
Collapse
|
|
28
|
Frequency of Helicobacter pylori hopQI, hopQII and sabA Genes Among Iranian Patients with Gastroduodenal Diseases. Jundishapur J Microbiol 2018. [DOI: 10.5812/jjm.56017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
|
|
29
|
Abstract
In addition to its role in gastric conditions,
Helicobacter pylori has been found to contribute to the development of several non-gastric issues in recent years. Eradication therapy is the only effective management strategy to minimize the
H. pylori-related gastric cancer and extra-gastric complications. For an effective “test and treat” strategy, diagnosis and therapy are both important. Because the infection is usually asymptomatic, patient selection is a critical issue for timely diagnosis and many clinical and demographic factors should be considered. Clarithromycin and metronidazole resistance rates also need to be considered while eradication therapy is offered. In this report, we discuss the issues which must be taken into account for the correct and timely diagnosis and for the antibiotic therapy-based management of
H. pylori infection.
Collapse
Affiliation(s)
- Shamshul Ansari
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita, 879-5593, Japan
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita, 879-5593, Japan.,Department of Medicine-Gastroenterology, Baylor College of Medicine, 2002 Holcombe Boulevard, Houston, TX, 77030, USA
| |
Collapse
|
|
30
|
Kato S, Osaki T, Kamiya S, Zhang XS, Blaser MJ. Helicobacter pylori sabA gene is associated with iron deficiency anemia in childhood and adolescence. PLoS One 2017; 12:e0184046. [PMID: 28854239 PMCID: PMC5576686 DOI: 10.1371/journal.pone.0184046] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 08/17/2017] [Indexed: 12/16/2022] Open
Abstract
Background Gastric Helicobacter pylori colonization leads to iron deficiency anemia (IDA), especially in children and adolescents. However the pathogenesis is poorly understood. Objective We sought to identify specific H. pylori genes involved in IDA development, by comparing bacterial genome-wide expression profiling in patients affected or not. Methods H. pylori were isolated from four children with IDA and four from matched controls without IDA. Based on these isolates, cDNA microarrays under iron-replete or depleted conditions were systematically performed to compare gene expression profiles at the whole genome level. Real-time reverse-transcription (RT-) PCR and protein assays were performed for further assessing the profile differentiation of the identified H. pylori IDA-associated genes. Results We identified 29 and 11 genes with significantly higher or lower expression in the IDA isolates compared to non-IDA isolates, respectively. Especially notable were higher expression of sabA gene encoding sialic acid-binding adhesin in the IDA isolates, which was confirmed by real-time RT-PCR study. Moreover, iron-depletion in vitro led to up-regulation of fecA1 and frpB1 genes and down-regulation of pfr, as predicted. Known iron-regulated genes such as fur, pfr, fecA, and feoB did not significantly differ between both groups. The IDA isolates had significantly higher expression of vacuolating cytotoxin gene vacA than non-IDA isolates, consistent with the results of VacA protein assays. There were no significant differences in bacterial growth value between IDA and non-IDA isolates. Conclusions It is likely that H. pylori carrying high expression of sabA causes IDA, especially in children and adolescents who have increased daily iron demand. In addition, it is possible that several host-interactive genes, including vacA, may play a synergistic role for sabA in IDA development.
Collapse
Affiliation(s)
- Seiichi Kato
- Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan
- Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Japan
- * E-mail:
| | - Takako Osaki
- Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Japan
| | - Shigeru Kamiya
- Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Japan
| | - Xue-Song Zhang
- Departments of Medicine and Microbiology, New York University School of Medicine, New York, NY, United States of America
| | - Martin J. Blaser
- Departments of Medicine and Microbiology, New York University School of Medicine, New York, NY, United States of America
| |
Collapse
|
|
31
|
Sohrabi M, Khashei R, Alizadeh M, Asl MKH, Nejati MA, Dara M, Bazargani A. Low Rate of babA2 Genotype among Iranian Helicobacter pylori Clinical Isolates. J Clin Diagn Res 2017; 11:DC32-DC36. [PMID: 28892894 DOI: 10.7860/jcdr/2017/24810.10277] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Accepted: 05/04/2017] [Indexed: 12/15/2022]
Abstract
INTRODUCTION The Blood Group Antigen-Binding Adhesion (babA), Outer Inflammatory Protein (oipA) and Sialic Acid-Binding Adhesin (sabA) as outer membrane proteins involved in Helicobacter pylori adherence to gastric mucosa have been suggested to have a role in the pathogenesis. AIM To investigate the frequency of H. pylori isolates babA2, oipA and sabA genes in Iranian dyspeptic patients. MATERIALS AND METHODS DNAs were extracted from H. pylori -positive cultures taken from 100 different dyspeptic patients. Genotyping was performed by Polymerase Chain Reaction (PCR), using the specific primers for babA2, oipA and sabA genes. Chi square test was used to investigate association between variables, p<0.05 was considered statistically significant. RESULTS All (100%) isolates possessed oipA and sabA genotypes, whereas babA2 was detected in 22% of isolates. There was no significant relationship between presence of genes with clinical outcome. The combined genotype oipA +/sabA +/ babA2- was correlated with gastritis. The rate of babA2 genotype in our isolates was lower than other Iranian reports. CONCLUSION Frequency of babA2 genotype among H. pylori isolates from Southwest of Iran is considerably less than other regions of Iran. Due to heterogeneity of H. pylori strains in different geographic regions, further work will be needed to understand the role of these virulence genes in H. pylori pathogenesis and their possible association with disease outcome.
Collapse
Affiliation(s)
- Maryam Sohrabi
- Student, Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Reza Khashei
- Assistant Professor, Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahvash Alizadeh
- Assistant Professor, Department of Internal Medicine, Gastroenterology Ward, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad-Kazem Hosseini Asl
- Associate Professor, Department of Internal Medicine, Gastroenterology Ward, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad-Ali Nejati
- Assistant Professor, Department of Internal Medicine, Gastroenterology Ward, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahintaj Dara
- Ph.D Student, Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Abdollah Bazargani
- Associate Professor, Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| |
Collapse
|
|
32
|
Acio-Pizzarello CR, Acio AA, Choi EJ, Bond K, Kim J, Kenan AC, Chen J, Forsyth MH. Determinants of the regulation of Helicobacter pylori adhesins include repeat sequences in both promoter and coding regions as well as the two-component system ArsRS. J Med Microbiol 2017; 66:798-807. [PMID: 28598306 DOI: 10.1099/jmm.0.000491] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
PURPOSE We investigated the transcription of adhesin-encoding genes sabA, hopZ and labA in Helicobacter pylori strain J99. Each possesses a repeating homopolymeric nucleotide tract within their promoter regions, and sabA and hopZ possess repeats within their 5' coding regions. METHODOLOGY We altered the repeat lengths associated with the adhesin genes and quantified mRNA levels by real-time quantitative PCR. Using adherence to AGS cells and IL-8 assays, we examined the effects of altered transcript levels. We assessed the role of ArsRS in transcription using an arsS null mutant and by examining ArsR binding to promoter regions via electrophoretic mobility shift assays. RESULTS Extensions or truncations of promoter region repeats in hopZ and labA increased transcript levels, mirroring results shown by our lab and others for mutations in the sabA promoter. Altered lengths of the poly-cytosine thymine tract within the 5' coding region of sabA demonstrated that switching from phase-off to phase-on significantly increased mRNA levels. However, mutations in the poly-thymine tract of sabA, which increased mRNA levels, do not behave synergistically with phase-on mutations. Phase-on mutations of sabA resulted in increased H. pylori adherence to AGS cells, but only a modest effect on IL-8. hopZ and labA, and sabA paralogue sabB, transcript levels were increased in an arsS mutant and ArsR bound the promoter regions for each of these genes in vitro. CONCLUSION This work highlights the complex nature of adhesin regulation, its impact on H. pylori attachment and the pervasive role of ArsRS in adhesin expression. Such regulation may help facilitate the decades-long persistence of infection.
Collapse
Affiliation(s)
- Catherine R Acio-Pizzarello
- Department of Biology, College of William and Mary, Williamsburg, VA, USA.,Present address: University of Rochester School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA
| | - Abigail A Acio
- Department of Biology, College of William and Mary, Williamsburg, VA, USA.,Present address: Department of Forensic Science, Pennsylvania State University, State College, PA, USA
| | - Edward J Choi
- Department of Biology, College of William and Mary, Williamsburg, VA, USA
| | - Kimberly Bond
- Department of Biology, College of William and Mary, Williamsburg, VA, USA
| | - June Kim
- Department of Biology, College of William and Mary, Williamsburg, VA, USA
| | - Anna C Kenan
- Department of Biology, College of William and Mary, Williamsburg, VA, USA
| | - Jiajia Chen
- Department of Biology, College of William and Mary, Williamsburg, VA, USA
| | - Mark H Forsyth
- Department of Biology, College of William and Mary, Williamsburg, VA, USA
| |
Collapse
|
|
33
|
Huang Y, Wang QL, Cheng DD, Xu WT, Lu NH. Adhesion and Invasion of Gastric Mucosa Epithelial Cells by Helicobacter pylori. Front Cell Infect Microbiol 2016; 6:159. [PMID: 27921009 PMCID: PMC5118847 DOI: 10.3389/fcimb.2016.00159] [Citation(s) in RCA: 97] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2016] [Accepted: 11/04/2016] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori is the main pathogenic bacterium involved in chronic gastritis and peptic ulcer and a class 1 carcinogen in gastric cancer. Current research focuses on the pathogenicity of H. pylori and the mechanism by which it colonizes the gastric mucosa. An increasing number of in vivo and in vitro studies demonstrate that H. pylori can invade and proliferate in epithelial cells, suggesting that this process might play an important role in disease induction, immune escape and chronic infection. Therefore, to explore the process and mechanism of adhesion and invasion of gastric mucosa epithelial cells by H. pylori is particularly important. This review examines the relevant studies and describes evidence regarding the adhesion to and invasion of gastric mucosa epithelial cells by H. pylori.
Collapse
Affiliation(s)
- Ying Huang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
| | - Qi-Long Wang
- Department of General Surgery, Tianjin Haihe Hospital Tianjin, China
| | - Dan-Dan Cheng
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
| | - Wen-Ting Xu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
| | - Nong-Hua Lu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
| |
Collapse
|
|
34
|
Su YL, Huang HL, Huang BS, Chen PC, Chen CS, Wang HL, Lin PH, Chieh MS, Wu JJ, Yang JC, Chow LP. Combination of OipA, BabA, and SabA as candidate biomarkers for predicting Helicobacter pylori-related gastric cancer. Sci Rep 2016; 6:36442. [PMID: 27819260 PMCID: PMC5098209 DOI: 10.1038/srep36442] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Accepted: 10/17/2016] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori (H. pylori ) infection is a major cause of chronic gastritis and is highly related to duodenal ulcer (DU) and gastric cancer (GC). To identify H. pylori-related GC biomarkers with high seropositivity in GC patients, differences in levels of protein expression between H. pylori from GC and DU patients were analyzed by isobaric tag for relative and absolute quantitation (iTRAQ). In total, 99 proteins showed increased expression (>1.5-fold) in GC patients compared to DU patients, and 40 of these proteins were categorized by KEGG pathway. The four human disease-related adhesin identified, AlpA, OipA, BabA, and SabA, were potential GC-related antigens, with a higher seropositivity in GC patients (n = 76) than in non-GC patients (n = 100). Discrimination between GC and non-GC patients was improved using multiple antigens, with an odds ratio of 9.16 (95% CI, 2.99-28.07; p < 0.0001) for three antigens recognized. The optimized combination of OipA, BabA, and SabA gave a 77.3% correct prediction rate. A GC-related protein microarray was further developed using these antigens. The combination of OipA, BabA, and SabA showed significant improvement in the diagnostic accuracy and the protein microarray containing above antigens should provide a rapid and convenient diagnosis of H. pylori-associated GC.
Collapse
Affiliation(s)
- Yu-Lin Su
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Hsiang-Ling Huang
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Bo-Shih Huang
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Po-Chung Chen
- Graduate Institute of Systems Biology and Bioinformatics, National Central University, Taoyuan, Taiwan
| | - Chien-Sheng Chen
- Graduate Institute of Systems Biology and Bioinformatics, National Central University, Taoyuan, Taiwan
| | - Hong-Long Wang
- Department of Statistics, National Taipei University, New Taipei City, Taiwan
| | - Pin-Hsin Lin
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Meng-Shu Chieh
- First Core Laboratory, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jiunn-Jong Wu
- Department of Medical Laboratory Science and Biotechnology, Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Jyh-Chin Yang
- Department of Internal Medicine, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Lu-Ping Chow
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
- Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan
| |
Collapse
|
|
35
|
Fucosyltransferase-4 and Oligosaccharide Lewis Y Antigen as potentially Correlative Biomarkers of Helicobacter pylori CagA Associated Gastric Cancer. Pathol Oncol Res 2016; 23:173-179. [PMID: 27757838 DOI: 10.1007/s12253-016-0122-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 10/04/2016] [Indexed: 12/20/2022]
Abstract
H. pylori cytotoxin associated antigen A (CagA) plays a significant role in the progression of gastric cancer but their effect on fucosylation to develop gastric cancer is unknown. Fucosyltransferase IV (FUT4) is the key enzyme for synthesis of LewisY (LeY) carried by glycoproteins and glycolipids on the cell membrane. Herein, we compare the expression of CagA, p-EGFR, FUT4 and LeY in gastritis (n = 128, 176), gastric ulcer (n = 174, 213), and gastric cancer (n = 323, 261) tissue and serum samples, respectively by IHC and ELISA. Moreover, we investigated the potential correlation of CagA with FUT4 and LeY overexpression through EGFR activation. IHC and ELISA results showed higher positive cases of H. pylori CagA (83, 86 %), p-EGFR (81, 72 %), FUT4 (91, 97 %) and LeY (93, 92 %) in gastric cancer, compared to gastritis and gastric ulcer, H. pylori CagA (58, 67 & 59, 73 %), p-EGFR (52, 63 & 35, 47 %), FUT4 (68, 78 & 67, 82 %) and LeY (62,76 & 65, 85 %), respectively. We found a significant high expression (H-Value) of CagA (1.79, 1.66), p-EGFR (1.53, 1.58), FUT4 (2.14, 1.66) and LeY (1.69, 1.61) in gastric cancer tissues and serum, respectively as compared to chronic gastritis and gastric ulcers, CagA (0.64,1.14), p-EGFR (0.856, 0.678), FUT4 (0.949,1.197) and LeY (0.68,1.008) (P < 0.0001), respectively. Furthermore, H. pylori CagA showed significant correlation with p-EGFR (R-0.62, -0.74), FUT4 (R-0.81, -0.76) and LeY (R-0.82, -0.70) in gastric tissues and serum (P < 0.0001). H. pylori CagA plays key role in the development of gastric cancer with overexpression of FUT4/LeY, serve as potentially correlative biomarkers of H. pylori CagA associated gastric cancer.
Collapse
|
|
36
|
Chi ZC. Update on prevention and treatment of Helicobacter pylori infection. Shijie Huaren Xiaohua Zazhi 2016; 24:2454-2462. [DOI: 10.11569/wcjd.v24.i16.2454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
From the first isolation of Helicobacter pylori (H. pylori) from the gastric mucosa by Marshall and Warren in 1983, 33 years have passed. H. pylori has been found to be closely associated not only with chronic gastric diseases but also with multiple system diseases. Advances in research of H. pylori infection has led to a better understanding of the pathogenicity of H. pylori and the prevention and treatment of related disease. In 2015, Professor Zou's team developed oral recombinant H. pylori vaccine, which is promising in the prevention of H. pylori infection. Japan aims to reduce the risk of H. pylori infection in the whole population in 2014 to reduce the incidence of gastric cancer, which has caused widespread concern. H. pylori infection is a kind of infectious disease, and the infection rate in China is about 56%.Therefore, it is of great clinical importance to strengthen the research on bacteriology and pathogenesis of H. pylori, improve the prevention and treatment related diseases, and seek antibacterial regimens with better efficacy and lower drug resistance.
Collapse
|
|
37
|
Wirth HP, Yang M. Different Pathophysiology of Gastritis in East and West? A Western Perspective. Inflamm Intest Dis 2016; 1:113-122. [PMID: 29922666 DOI: 10.1159/000446300] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2016] [Accepted: 04/13/2016] [Indexed: 12/11/2022] Open
Abstract
Background Gastritis results from multifactorial gastric mucosal injury. Helicobacter pylori (Hp) is the main cause, and associated diseases have typical underlying patterns of gastritis. Gastric ulcer and gastric cancer (GC) develop from chronic atrophic corpus gastritis (CAG) which therefore represents the most important pattern. GC incidences in East Asia are substantially higher than elsewhere, and this should be also reflected by higher prevalences of CAG and characteristic differences in pathophysiology compared to the West. Summary The few available comparative studies of gastritis in Eastern and Western patients are summarized. The main pathogenic factors of gastritis are discussed together with their limitations to explain local differences in disease outcome. Emphasis was put to also include less well-established pathogenic host and environmental factors of possible impact. Conclusions CAG is more prevalent in East Asian areas with high GC incidences than the West. Geographic heterogeneity of associated diseases is due to differences in Hp prevalence and virulence as well as modulating host and environmental factors. The following may contribute to the higher burden of CAG in the East: ABD type of CagA with vacA s1 and babA2 alleles of Hp, host Lewis(b) expression in sej/sej nonsecretors, H. heilmannii, low parietal cell mass, high sodium and nitrate intake, preferences in vegetable and fruit consumption, cigarette smoking, air pollution, alcohol. Conversely, green tea, nonfermented soy products and rice may confer protective effects. Hp is on the decline, but also in a world cleared from this bacterium, differences in host genetics will continue to modify gastric disease outcome together with maintained customs as part of cultural diversity.
Collapse
Affiliation(s)
| | - Manqiao Yang
- GastroZentrumKreuzlingen, Kreuzlingen, Switzerland
| |
Collapse
|
|
38
|
Ji HG, Piao JY, Kim SJ, Kim DH, Lee HN, Na HK, Surh YJ. Docosahexaenoic acid inhibits Helicobacter pylori-induced STAT3 phosphorylation through activation of PPARγ. Mol Nutr Food Res 2016; 60:1448-57. [PMID: 27079734 DOI: 10.1002/mnfr.201600009] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Revised: 03/08/2016] [Accepted: 03/09/2016] [Indexed: 01/09/2023]
Abstract
SCOPE The health beneficial effects of docosahexaenoic acid (DHA) have been attributed to its anti-inflammatory properties. However, the molecular mechanism underlying anti-inflammatory effects of DHA remains largely elusive. METHODS AND RESULTS In the present study, DHA was found to suppress the phosphorylation and nuclear translocation of signal transducer and activator of transcription 3 (STAT3) induced by Helicobacter pylori infection in human gastric cancer AGS cells. Notably, DHA induced expression of suppressor of cytokine signaling 3 (SOCS3), a negative regulator of STAT3. Knockdown of SOCS3 abolished the suppressive effect of DHA on STAT3(Tyr705) phosphorylation induced by H. pylori infection. DHA also induced nuclear translocation, DNA binding, and transcriptional activities of peroxisome proliferator-activated receptor gamma (PPARγ) in AGS cells. Knockdown of PPARγ inhibited the transcription of SOCS3 and attenuated the suppressive effect of DHA on phosphorylation of STAT3(Tyr705) induced by H. pylori. The PPARγ antagonist bisphenol A diglycidyl ether also mitigated the suppressive effect of DHA on H. pylori-induced phosphorylation of STAT3(Tyr705) . In addition, DHA inhibited the expression of c-Myc, which was attenuated in the AGS cells harboring SOCS3 specific siRNA. DHA also markedly decreased anchorage-independent growth of AGS cells infected by H. pylori. CONCLUSION DHA inhibits H. pylori-induced STAT3 phosphorylation in a PPARγ/SOCS3-dependent manner.
Collapse
Affiliation(s)
- Hyeon-Geun Ji
- Cancer Research Institute, Seoul National University, Seoul, South Korea.,Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea
| | - Juan-Yu Piao
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea
| | - Su-Jung Kim
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Sciences, Seoul, South Korea
| | - Do-Hee Kim
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea
| | - Ha-Na Lee
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea
| | - Hye-Kyung Na
- Department of Food and Nutrition, College of Human Ecology, Sungshin Women's University, Seoul, South Korea
| | - Young-Joon Surh
- Cancer Research Institute, Seoul National University, Seoul, South Korea.,Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea.,Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Sciences, Seoul, South Korea
| |
Collapse
|
|
39
|
Zhang RG, Duan GC, Fan QT, Chen SY. Role of Helicobacter pylori infection in pathogenesis of gastric carcinoma. World J Gastrointest Pathophysiol 2016; 7:97-107. [PMID: 26909232 PMCID: PMC4753193 DOI: 10.4291/wjgp.v7.i1.97] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 09/18/2015] [Accepted: 11/04/2015] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is one of the most common carcinoma and the second leading cause of cancer-related deaths worldwide. Helicobacter pylori (H. pylori) infection causes a series of precancerous lesions like gastritis, atrophy, intestinal metaplasia and dysplasia, and is the strongest known risk factor for GC, as supported by epidemiological, preclinical and clinical studies. However, the mechanism of H. pylori developing gastric carcinoma has not been well defined. Among infected individuals, approximately 10% develop severe gastric lesions such as peptic ulcer disease, 1%-3% progresses to GC. The outcomes of H. pylori infection are determined by bacterial virulence, genetic polymorphism of hosts as well as environmental factors. It is important to gain further understanding of the pathogenesis of H. pylori infection for developing more effective treatments for this common but deadly malignancy. The recent findings on the bacterial virulence factors, effects of H. pylori on epithelial cells, genetic polymorphism of both the bacterium and its host, and the environmental factors for GC are discussed with focus on the role of H. pylori in gastric carcinogenesis in this review.
Collapse
|
|
40
|
Keilberg D, Ottemann KM. HowHelicobacter pylorisenses, targets and interacts with the gastric epithelium. Environ Microbiol 2016; 18:791-806. [DOI: 10.1111/1462-2920.13222] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2015] [Revised: 01/05/2016] [Accepted: 01/10/2016] [Indexed: 12/18/2022]
Affiliation(s)
- Daniela Keilberg
- Department of Microbiology and Environmental Toxicology; University of California Santa Cruz; 1156 High Street METX Santa Cruz CA 95064 USA
| | - Karen M. Ottemann
- Department of Microbiology and Environmental Toxicology; University of California Santa Cruz; 1156 High Street METX Santa Cruz CA 95064 USA
| |
Collapse
|
|
41
|
Kim N, Park YH. Atrophic Gastritis and Intestinal Metaplasia. HELICOBACTER PYLORI 2016:187-206. [DOI: 10.1007/978-981-287-706-2_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
42
|
Homan M, Orel R. Are probiotics useful in Helicobacter pylori eradication? World J Gastroenterol 2015; 21:10644-10653. [PMID: 26457024 PMCID: PMC4588086 DOI: 10.3748/wjg.v21.i37.10644] [Citation(s) in RCA: 91] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2015] [Revised: 04/25/2015] [Accepted: 09/02/2015] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori (H. pylori) is considered an etiologic factor for the development of peptic ulcer disease, gastric adenocarcinoma, and MALT lymphoma. Therapeutic schemes to eradicate the bacteria are based on double antibiotic therapy and proton pump inhibitor. Despite many therapeutic improvements in H. pylori eradication treatment, it is still associated with high infection rate also in developed countries. Bacterial resistance and adverse events occurrence are among most frequent causes for anti- H. pylori treatment failure. Several studies have reported that certain probiotic strains can exhibit inhibitory activity against H. pylori bacteria. In addition, some probiotic strains can reduce the occurrence of side effects due to antibiotic therapy and consequently increase the H. pylori eradication rate. The results of the prospective double-blind placebo-controlled studies suggest that specific probiotics, such as S. boulardii and L. johnsonni La1 probably can diminish the bacterial load, but not completely eradicate the H. pylori bacteria. Furthermore, it seems that supplementation with S. boulardii is a useful concomitant therapy in the standard H. pylori eradication treatment protocol and most probably increases eradication rate. L. reuteri is equally effective, but more positive studies are needed. Finally, probiotic strains, such as S. boulardii, L. reuteri and L. GG, decrease gastrointestinal antibiotic associated adverse effects.
Collapse
|
|
43
|
Subhash VV, Ho B. Inflammation and proliferation - a causal event of host response to Helicobacter pylori infection. MICROBIOLOGY (READING, ENGLAND) 2015; 161:1150-1160. [PMID: 25721850 DOI: 10.1099/mic.0.000066] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Helicobacter pylori is a major aetiological agent in the development of various gastroduodenal diseases. Its persistence in gastric mucosa is determined by the interaction between various host, microbial and environmental factors. The bacterium colonizes the gastric epithelium and induces activation of various chemokine mediators, including NFκB, the master regulator of inflammation. H. pylori infection is also associated with an increase in expression of cell cycle regulators, thereby leading to mucosal cell hyper-proliferation. Thus, H. pylori-associated infections manifest activation of key host response events, which inadvertently could lead to the establishment of chronic infection and neoplastic progression. This article reviews and elaborates the current knowledge in H. pylori-induced activation of various host signalling pathways that could promote cancer development. Special focus is placed on the inflammatory and proliferative responses that could serve as suitable biomarkers of infection, since a sustained cell proliferation in an environment rich in inflammatory cells is characteristic in H. pylori-associated gastric malignancies. Here, the role of ERK and WNT signalling in H. pylori-induced activation of inflammatory and proliferative responses respectively is discussed in detail. An in depth analysis of the underlying signalling pathways and interacting partners causing alterations in these crucial host responses could contribute to the development of successful therapeutic strategies for the prevention, management and treatment of H. pylori infection.
Collapse
Affiliation(s)
- Vinod Vijay Subhash
- Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 117545, Singapore
| | - Bow Ho
- Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 117545, Singapore
| |
Collapse
|
|
44
|
Park YH, Kim N. Review of atrophic gastritis and intestinal metaplasia as a premalignant lesion of gastric cancer. J Cancer Prev 2015; 20:25-40. [PMID: 25853101 PMCID: PMC4384712 DOI: 10.15430/jcp.2015.20.1.25] [Citation(s) in RCA: 204] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2015] [Revised: 03/18/2015] [Accepted: 03/18/2015] [Indexed: 12/14/2022] Open
Abstract
Atrophic gastritis (AG) and intestinal metaplasia (IM) are the main precursor lesions of gastric cancer as the incidence of gastric cancer increases in the gastric mucosa involved with AG and IM. The prevalence of AG and IM vary depending on countries, even it represents diverse results in the same nation. Usually AG is antecedent of IM but the etiologies of AG and IM are not always the same. The sensitivity and specificity of diagnostic methods to detect AG and IM are different. Furthermore, the management strategy of AG and IM has not been established, yet. Helicobacter pylori infection has been proved as the most important cause of AG and IM. Thus the eradication of H. pylori is very important to prevent the progression to gastric cancer which is still placed in the high rank in morbidity and mortality among cancers. However, the reversibility of AG and IM by eradication of H. pylori which was assumed to be certain by meta-analysis is; however, controversial now. Therefore, the understanding and early diagnosis of AG and IM are very important, especially, in high incidence area of gastric cancer such as Republic of Korea.
Collapse
Affiliation(s)
- Yo Han Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam ; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| |
Collapse
|
|
45
|
Ghatak S, Sanga Z, Pautu JL, Kumar NS. Coextraction and PCR Based Analysis of Nucleic Acids From Formalin-Fixed Paraffin-Embedded Specimens. J Clin Lab Anal 2014; 29:485-92. [PMID: 25277467 DOI: 10.1002/jcla.21798] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2014] [Revised: 05/12/2014] [Accepted: 08/07/2014] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Retrospective studies of archived human specimens, with known clinical follow-up, are used to identify predictive and prognostic molecular markers of disease. Due to biochemical differences, however, formalin-fixed paraffin embedded (FFPE) DNA and RNA have generally been extracted separately from either different tissue sections or from the same section by dividing the digested tissue. Our optimized co-extraction approach provides the option of collecting DNA, which would otherwise be discarded or degraded, for additional or subsequent studies because of the high importance and less availability of clinical FFPE specimen. METHODS Coextraction of DNA and RNA from a single gastric cancer FFPE specimen was optimized by using TRIzol and purifying DNA from the lower aqueous and RNA from the upper organic phases. The protocol involves modification of incubation period for 30 min with proteinase K in glycin-tris-ethylenediamine tetra acetic acid buffer before adding TRIzol. RESULTS All samples tested successfully performed semiquantitative gene expression by reverse transcriptase PCR. The quantity and quality of DNA from FFPE samples was high which resulted in successful PCR amplification. The isolated DNA also aided in detection of Helicobacter pylori by amplifying the ribosomal 16S gene in a multiplex PCR reaction along with cagA. CONCLUSION These results show that the RNA/DNA isolated by this method can be used for easy clinical diagnosis of disease-related gene expression as well as mutation and pathogen detection from a homogenous population of tumor cells.
Collapse
Affiliation(s)
- Souvik Ghatak
- Department of Biotechnology, Mizoram University, Aizawl, Mizoram, India
| | - Zothan Sanga
- Department of Biotechnology, Mizoram University, Aizawl, Mizoram, India
| | - Jeremy L Pautu
- Mizoram State Cancer Institute, Zemabawk, Aizawl, Mizoram, India
| | | |
Collapse
|
|
46
|
Raza Y, Khan A, Farooqui A, Mubarak M, Facista A, Akhtar SS, Khan S, Kazi JI, Bernstein C, Kazmi SU. Oxidative DNA damage as a potential early biomarker of Helicobacter pylori associated carcinogenesis. Pathol Oncol Res 2014; 20:839-846. [PMID: 24664859 DOI: 10.1007/s12253-014-9762-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2013] [Accepted: 03/06/2014] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori infection is an established risk factor for gastritis, gastric ulcer, peptic ulcer and gastric cancer. CagA +ve H. pylori has been associated with oxidative DNA damage of gastric mucosa but their combined role in the development of gastric cancer is still unknown. Here we compare the combined expression of cagA and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in normal, gastritis and gastric cancer tissues. Two hundred gastric biopsies from patients with dyspeptic symptoms, 70 gastric cancer tissue samples and 30 gastric biopsies from non-dyspeptic individuals (controls) were included in this study and 8-OHdG was detected by immunohistochemistry (IHC). Histological features and the presence of H. pylori infection were demonstrated by Hematoxylin and Eosin (HE), Giemsa and alcian blue-periodic acid-Schiff ± diastase (AB-PAS ± D) staining. DNA was extracted from tissues and polymerase chain reaction (PCR) performed to determine the presence of ureaseA and cagA genes of H. pylori. The results showed the presence of H. pylori in 106 (53 %) gastric biopsies out of 200 dyspeptic patients, including 70 (66 %) cases of cagA + ve H. pylori. The presence of cagA gene and high expression of 8-OHdG was highly correlated with severe gastric inflammation and gastric cancer particularly, in cases with infiltration of chronic inflammatory cells (36.8 % cagA + ve, 18 %), neutrophilic activity (47.2 %, 25.5 %), intestinal metaplasia (77.7 %, 35.7 %) and intestinal type gastric cancer (95 %, 95.4 %) (p ≤ 0.01). In conclusion, H. Pylori cagA gene expression and the detection of 8-OHdG adducts in gastric epithelium can serve as potential early biomarkers of H. Pylori-associated gastric carcinogenesis.
Collapse
Affiliation(s)
- Yasir Raza
- Immunology and Infectious Diseases Research Laboratory, Department of Microbiology, University of Karachi, Karachi, Pakistan,
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
47
|
Landarani Z, Falsafi T, Mahboubi M, Lameh-rad B. Immunological detection of 34 KDa outer membrane protein as a functional form of OipA in clinical isolates of Helicobacter pylori. IRANIAN JOURNAL OF MICROBIOLOGY 2014; 6:324-329. [PMID: 25848522 PMCID: PMC4385572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
BACKGROUND AND OBJECTIVE An outer membrane protein (OMP) of Helicobacter pylori namely OipA, is an important virulence factor associated with peptic ulcer and gastric cancer risks. The purpose of this study was to isolate the 34 KDa OMP of H. pylori and evaluate its immunogenicity in experimental animals for rapid detection of more virulent H. pylori isolates. MATERIAL AND METHODS Sarcosine insoluble fraction of membrane proteins (OMPs) were prepared from 15 clinical isolates of H. pylori and their profiles were analyzed by SDS-PAGE. Two out of 15 isolates which demonstrated higher expression for apparent 34 KDa proteins were selected. Under optimal conditions, 34 KDa protein was recovered from 5% SDS-Agarose gel, purified and injected into the New Zealand white rabbits with Fruend's adjuvant in multiple stages with two weeks intervals. Collected antiserum was purified through affinity chromatography with Sepharose column and its titer was determined by ELISA. Specific immune response was demonstrated by Dot blot and western blotting methods. RESULTS The titer of antibody was determined about 1/3000 and western blotting demonstrated a 34 KD-protein. Screening of various strains by Dot blot method for its presence showed that its expression was more frequent in strains isolated from the patients with more severe pathology. CONCLUSION High titer obtained for pAbs antibody, suggested the high immunogenicity of this protein in experimental animals. Detection of 34 KDa OMP in strains isolated from the patients with more severe pathology proposes the possible application of this pAbs in detecting more virulent strains of H. pylori.
Collapse
Affiliation(s)
- Zahra Landarani
- Department of Biology, Alzahra University, Tehran, Iran
- Department of Biochemistry, Payam-Nour University, Tehran, Iran
| | | | | | | |
Collapse
|
|
48
|
Repetitive sequence variations in the promoter region of the adhesin-encoding gene sabA of Helicobacter pylori affect transcription. J Bacteriol 2014; 196:3421-9. [PMID: 25022855 DOI: 10.1128/jb.01956-14] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
The pathogenesis of diseases elicited by the gastric pathogen Helicobacter pylori is partially determined by the effectiveness of adaptation to the variably acidic environment of the host stomach. Adaptation includes appropriate adherence to the gastric epithelium via outer membrane protein adhesins such as SabA. The expression of sabA is subject to regulation via phase variation in the promoter and coding regions as well as repression by the two-component system ArsRS. In this study, we investigated the role of a homopolymeric thymine [poly(T)] tract -50 to -33 relative to the sabA transcriptional start site in H. pylori strain J99. We quantified sabA expression in H. pylori J99 by quantitative reverse transcription-PCR (RT-PCR), demonstrating significant changes in sabA expression associated with experimental manipulations of poly(T) tract length. Mimicking the length increase of this tract by adding adenines instead of thymines had similar effects, while the addition of other nucleotides failed to affect sabA expression in the same manner. We hypothesize that modification of the poly(T) tract changes DNA topology, affecting regulatory protein interaction(s) or RNA polymerase binding efficiency. Additionally, we characterized the interaction between the sabA promoter region and ArsR, a response regulator affecting sabA expression. Using recombinant ArsR in electrophoretic mobility shift assays (EMSA), we localized binding to a sequence with partial dyad symmetry -20 and +38 relative to the sabA +1 site. The control of sabA expression by both ArsRS and phase variation at two distinct repeat regions suggests the control of sabA expression is both complex and vital to H. pylori infection.
Collapse
|
|
49
|
Prevalence and correlation with clinical diseases of Helicobacter pylori cagA and vacA genotype among gastric patients from Northeast China. BIOMED RESEARCH INTERNATIONAL 2014; 2014:142980. [PMID: 24949419 PMCID: PMC4052682 DOI: 10.1155/2014/142980] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 04/02/2014] [Accepted: 04/23/2014] [Indexed: 12/12/2022]
Abstract
Helicobacter pylori vacA and cagA genes have significant genetic heterogenicity, resulting in different clinical outcomes. Northeast part of China has reported high prevalence of H. pylori infections and gastric cancer. Hence, we investigated the H. pylori cagA and vacA genotypes with clinical outcomes in Northeast China. Gastric tissue samples (n = 169), chronic gastritis (GIs), gastric ulcer (GU), and gastric cancer (GC) were analysed for 16S rRNA ureA, cagA, and cagA genotypes by PCR. A total of 141 (84%) cases were found positive for H. pylori by 16S rRNA and ureA. GC showed high H. pylori infection (93%) compared with GIs (72%) and GU (84%). The vacAs1am1 was highly found in GC (40%) and GU (36%), vacAs1am2 in GIs (33%), vacAs1bm1 (14%) and vacAs1bm2 (8%) in GU cases, and s2m1 in normal cases (33%), while vacAs1cm1 showed low frequency in GIs (2%) and GU (3%) and GC showed negative result. The East-Asian cagA strain was highly observed in GC (43%), as compared to GIs (41%) and GU (20%). The East-Asian cagA/vacAs1am1 was significantly higher in GC (23%) than in GU (22%) and GIs (145) patients. The East-Asian type cagA with vacAs1a and vacAm1 is the most predominant genotype in H. pylori strains of Northeast China.
Collapse
|
|
50
|
Abstract
BACKGROUND CagA+ and vacuolizing cytotoxin (VacA)-specific strains of Helicobacter pylori have been associated with different risks for developing gastric lesions. We aim to summarize a possible association between these genotypes and the risk for developing different gastric phenotypes. MATERIALS AND METHODS A MEDLINE database (PubMed) search was performed and a meta-analysis conducted. RESULTS Forty-four studies were retrieved, all with either a case-control (n=13) or cross-sectional (n=31) design, including 17 374 patients. CagA positivity was associated with an increased risk for gastric cancer [odds ratio (OR) 2.09 (95% confidence interval (CI), 1.48-2.94)] compared with that in individuals without gastric lesions [OR 2.44 (95% CI 1.27-4.70)] and in those with previously identified gastritis. In addition, there was an increased risk for peptic ulcer disease [OR 1.69 (95% CI 1.12-2.55)]. Individuals harboring the H. pylori strains VacA s1 (vs. s2), m1 (vs. m2), s1m1 (vs. s1m2), and s1m1 (vs. s2m2) had an increased risk for development of cancer [OR of 5.32 (95% CI 2.76-10.26), 2.50 (95% CI 1.67-3.750), 2.58 (95% CI 1.24-5.38), and 4.36 (95% CI 2.08-9.10), respectively]. s1m1 strains (vs. s2m2) were also associated with peptic ulcer disease [OR 2.04 (1.01-4.13)]. CONCLUSION Our results indicate that individuals infected with CagA+ H. pylori strains and those infected with VacA s1 and m1 strains have an increased risk for gastric cancer. Cohort studies are welcome to integrate this information in the management of at-risk individuals such as those with precancerous cancer conditions and/or a family history of gastric cancer.
Collapse
|