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Duan Y, Xu Y, Dou Y, Xu D. Helicobacter pylori and gastric cancer: mechanisms and new perspectives. J Hematol Oncol 2025; 18:10. [PMID: 39849657 PMCID: PMC11756206 DOI: 10.1186/s13045-024-01654-2] [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: 08/20/2024] [Accepted: 12/23/2024] [Indexed: 01/25/2025] Open
Abstract
Gastric cancer remains a significant global health challenge, with Helicobacter pylori (H. pylori) recognized as a major etiological agent, affecting an estimated 50% of the world's population. There has been a rapidly expanding knowledge of the molecular and pathogenetic mechanisms of H. pylori over the decades. This review summarizes the latest research advances to elucidate the molecular mechanisms underlying the H. pylori infection in gastric carcinogenesis. Our investigation of the molecular mechanisms reveals a complex network involving STAT3, NF-κB, Hippo, and Wnt/β-catenin pathways, which are dysregulated in gastric cancer caused by H. pylori. Furthermore, we highlight the role of H. pylori in inducing oxidative stress, DNA damage, chronic inflammation, and cell apoptosis-key cellular events that pave the way for carcinogenesis. Emerging evidence also suggests the effect of H. pylori on the tumor microenvironment and its possible implications for cancer immunotherapy. This review synthesizes the current knowledge and identifies gaps that warrant further investigation. Despite the progress in our previous knowledge of the development in H. pylori-induced gastric cancer, a comprehensive investigation of H. pylori's role in gastric cancer is crucial for the advancement of prevention and treatment strategies. By elucidating these mechanisms, we aim to provide a more in-depth insights for the study and prevention of H. pylori-related gastric cancer.
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Affiliation(s)
- Yantao Duan
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yonghu Xu
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yi Dou
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Dazhi Xu
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
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Xue Z, Li W, Ding H, Pei F, Zhang J, Gong Y, Fan R, Wang F, Wang Y, Chen Q, Li Y, Yang X, Zheng Y, Su G. Virulence gene polymorphisms in Shandong Helicobacter pylori strains and their relevance to gastric cancer. PLoS One 2024; 19:e0309844. [PMID: 39250512 PMCID: PMC11383249 DOI: 10.1371/journal.pone.0309844] [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: 03/21/2024] [Accepted: 08/20/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) virulence factors, particularly the cagA and vacA genotypes, play important roles in the pathogenic process of gastrointestinal disease. METHODS The cagA and vacA genotypes of 87 H. pylori strains were determined by PCR and sequencing. The EPIYA and CM motif patterns were analyzed and related to clinical outcomes. We examined the associations between the virulence genes of H. pylori and gastrointestinal diseases in Shandong, and the results were analyzed via the chi-square test and logistic regression model. RESULTS Overall, 76 (87.36%) of the strains carried the East Asian-type CagA, with the ABD types being the most prevalent (90.79%). However, no significant differences were observed among the different clinical outcomes. The analysis of CagA sequence types revealed 8 distinct types, encompassing 250 EPIYA motifs, including 4 types of EPIYA or EPIYA-like sequences. Additionally, 28 CM motifs were identified, with the most prevalent patterns being E (66.67%), D (16.09%), and W-W (5.75%). Notably, a significant association was discovered between strains with GC and the CM motif pattern D (P < 0.01). With respect to the vacA genotypes, the strains were identified as s1, s2, m1, m2, i1, i2, d1, d2, c1, and c2 in 87 (100%), 0 (0), 26 (29.89%), 61 (70.11%), 73 (83.91%), 14 (16.09%), 76 (87.36%), 11 (12.64%), 18 (20.69%), and 69 (79.31%), respectively. Specifically, the vacA m1 and c1 genotypes presented a significantly greater prevalence in strains from GC compared to CG (P < 0.05). Following adjustment for age and sex, the vacA c1 genotype demonstrated a notable association with GC (OR = 5.174; 95% CI, 1.402-20.810; P = 0.012). This association was both independent of and more pronounced than the correlations between vacA m1 and GC. CONCLUSIONS CagA proteins possessing CM motif pattern D were more frequently observed in patients with GC (P < 0.01), implying a potentially higher virulence of CM motif pattern D than the other CM motif patterns. Moreover, a strong positive association was identified between the vacA c1 genotype and GC, indicating that the vacA c1 genotype is a robust risk indicator for GC among male patients aged ≥55 years in Shandong.
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Affiliation(s)
- Zhijing Xue
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Weijia Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Hailing Ding
- The Faculty of Medicine, Qilu Institute of Technology, Jinan, Shandong, China
| | - Fengyan Pei
- Medical Research & Laboratory Diagnostic Center, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Jianzhong Zhang
- National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Yanan Gong
- National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Ruyue Fan
- Shandong Center for Disease Control and Prevention, Jinan, Shandong, China
| | - Fang Wang
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Youjun Wang
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Qing Chen
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Yanran Li
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Xinyu Yang
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Yan Zheng
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Guohai Su
- Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Department of Cardiovascular Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
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Nguyen TMN, Tran VH, Ha TMT. Helicobacter pylori cagA, vacA, and iceA genotypes and clinical outcomes: a cross-sectional study in central Vietnam. Braz J Microbiol 2024; 55:1393-1404. [PMID: 38676790 PMCID: PMC11153385 DOI: 10.1007/s42770-024-01328-8] [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: 09/09/2023] [Accepted: 04/01/2024] [Indexed: 04/29/2024] Open
Abstract
Helicobacter pylori is the most common cause of gastroduodenal diseases. The concept that cagA-positive H. pylori is a risk factor for gastric cancer appears to be true only for H. pylori strains from Western countries. Other virulent genes may have a synergistic interaction with cagA during pathogenesis. This study aims to investigate H. pylori cagA, vacA, and iceA prevalence, genotypes, and their association to clinical outcomes in Vietnamese patients. The cagA status and vacA and iceA genotypes were determined using the PCR technique on DNA extracted from gastric biopsies of 141 patients with gastroduodenal diseases. After performing molecular analysis for cagA, vacA, and iceA genes, samples with mixed H. pylori strains, positivity, or negativity for both cagA and cagPAI-empty site, or unidentified genotypes were excluded. Finally, 107 samples were examined. The presence of the cagA, vacA, and iceA genes were detected in 77.6%, 100%, and 80.4% of cases, respectively. Notably, cagA( +) with EPIYA-ABD, vacA s1i1m1, vacA s1i1m2, iceA1, and iceA2 accounted for 73.8%, 44.9%, 33.6%, 48.6%, and 31.8% of cases, respectively. Four iceA2 subtypes (24-aa, 59-aa, 94-aa, and 129-aa variants) were found, with the 59-aa variant the most prevalent (70.6%). The cagA( +)/vacAs1i1m1/iceA1 and cagA( +)/vacAs1i1m2/iceA1 combinations were found in 26.2% and 25.1% of cases, respectively. A multivariable logistic regression analysis was performed, after adjusting for age and gender, with the gastritis group was used as a reference control. Statistically significant associations were found between the vacA s1i1m2 genotype, the iceA1 variant, and the cagA( +)/vacAs1i1m2/iceA1 combination and gastric cancer; the adjusted ORs were estimated as 18.02 (95% CI: 3.39-95.81), 4.09 (95% CI: 1.1-15.08), and 16.19 (95% CI: 3.42-76.66), respectively. Interestingly, for the first time, our study found that vacA s1i1m2, but not vacA s1i1m1, was a risk factor for gastric cancer. This study illustrates the genetic diversity of the H. pylori cagA, vacA, and iceA genes across geographical regions and contributes to understanding the importance of these genotypes for clinical outcomes.
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Affiliation(s)
- Thi Mai Ngan Nguyen
- Department of Medical Genetics, University of Medicine and Pharmacy, Hue University, 6, Ngo Quyen Street, Hue City, 49100, Vietnam
| | - Van Huy Tran
- Department of Internal Medicine, University of Medicine and Pharmacy, Hue University, Hue City, Vietnam
- Centre of Gastroenterology and Endoscopy, University of Medicine and Pharmacy Hospital, Hue University, Hue City, Vietnam
| | - Thi Minh Thi Ha
- Department of Medical Genetics, University of Medicine and Pharmacy, Hue University, 6, Ngo Quyen Street, Hue City, 49100, Vietnam.
- Institute of Biomedicine, University of Medicine and Pharmacy, Hue University, Hue City, Vietnam.
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Garg A, Karhana S, Khan MA. Nanomedicine for the eradication of Helicobacter pylori: recent advances, challenges and future perspective. Future Microbiol 2024; 19:431-447. [PMID: 38381027 DOI: 10.2217/fmb-2023-0189] [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: 08/23/2023] [Accepted: 10/31/2023] [Indexed: 02/22/2024] Open
Abstract
Helicobacter pylori infection is linked to gastritis, ulcers and gastric cancer. Nanomedicine offers a promising solution by utilizing nanoparticles for precise drug delivery, countering antibiotic resistance and delivery issues. Nanocarriers such as liposomes and nanoparticles enhance drug stability and circulation, targeting infection sites through gastric mucosa characteristics. Challenges include biocompatibility, stability, scalability and personalized therapies. Despite obstacles, nanomedicine's potential for reshaping H. pylori eradication is significant and showcased in this review focusing on benefits, limitations and future prospects of nanomedicine-based strategies.
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Affiliation(s)
- Aakriti Garg
- Department of Pharmacology, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India
- Centre for Translational & Clinical Research, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi, 110062, India
| | - Sonali Karhana
- Centre for Translational & Clinical Research, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi, 110062, India
| | - Mohd A Khan
- Centre for Translational & Clinical Research, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi, 110062, India
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Jarzab M, Skorko-Glonek J. There Are No Insurmountable Barriers: Passage of the Helicobacter pylori VacA Toxin from Bacterial Cytoplasm to Eukaryotic Cell Organelle. MEMBRANES 2023; 14:11. [PMID: 38248700 PMCID: PMC10821523 DOI: 10.3390/membranes14010011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 12/20/2023] [Accepted: 12/23/2023] [Indexed: 01/23/2024]
Abstract
The Gram-negative bacterium Helicobacter pylori is a very successful pathogen, one of the most commonly identified causes of bacterial infections in humans worldwide. H. pylori produces several virulence factors that contribute to its persistence in the hostile host habitat and to its pathogenicity. The most extensively studied are cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA). VacA is present in almost all H. pylori strains. As a secreted multifunctional toxin, it assists bacterial colonization, survival, and proliferation during long-lasting infections. To exert its effect on gastric epithelium and other cell types, VacA undergoes several modifications and crosses multiple membrane barriers. Once inside the gastric epithelial cell, VacA disrupts many cellular-signaling pathways and processes, leading mainly to changes in the efflux of various ions, the depolarization of membrane potential, and perturbations in endocytic trafficking and mitochondrial function. The most notable effect of VacA is the formation of vacuole-like structures, which may lead to apoptosis. This review focuses on the processes involved in VacA secretion, processing, and entry into host cells, with a particular emphasis on the interaction of the mature toxin with host membranes and the formation of transmembrane pores.
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Affiliation(s)
| | - Joanna Skorko-Glonek
- Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland;
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Hassuna NA, Hussien SS, Abdelhakeem M, Aboalela A, Ahmed E, Abdelrahim SS. Regulatory B cells (Bregs) in Helicobacter pylori chronic infection. Helicobacter 2023; 28:e12951. [PMID: 36661205 DOI: 10.1111/hel.12951] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 01/01/2023] [Accepted: 01/04/2023] [Indexed: 01/21/2023]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection is linked with a wide variety of diseases and was reported in more than half of the world's population. Chronic H. pylori infection and its final clinical outcome depend mainly on the bacterial virulence factors and its ability to manipulate and adapt to human immune responses. Bregs blood levels have been correlated with increased bacterial load and infection chronicity, especially Gram-negative bacterial infection. This study aimed to identify prevalence and virulence factors of chronic H. pylori infection among symptomatic Egyptian patients and to examine its possible correlation to levels of regulatory B cells (Bregs) in blood. MATERIALS AND METHODS Gastric biopsies and blood samples from each of 113 adult patients, who underwent upper endoscopy, were examined for the detection of H. pylori by culture and PCR methods. Conventional PCR was used to determine various virulent genes prevalence and association to clinical outcome. Flow cytometry was used to evaluate Bregs levels. RESULTS Helicobacter pylori prevalence was 49.1% (55/112). Regarding virulence genes incidence, flaA gene was detected in 73% (40/55), vir B11 in 56.4% (31/55), hopZ1 in 34.5% (19/55), hopZ2 in 89% (49/55), babA2 in 52.7% (29/55), dupA jhp917 in 61.8% (34/55), vacA m1/m2 in 70.9% (39/55), and vacA s1/s2 in 69% (38/55) strains. Bregs levels were significantly lower in H. pylori-infected patients (p = 0.013), while total leukocyte count (TLC) showed no significant differences. CONCLUSION Helicobacter pylori infection prevalence was almost 49%, and the infection was found to be related to inflammatory conditions as gastritis and ulcers rather than malignant transformations. Also, we found that CD24+ CD38+ B cells were downregulated in H. pylori-infected patients.
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Affiliation(s)
- Noha A Hassuna
- Medical Microbiology and Immunology Department, Faculty of Medicine, Minia University, Minia, Egypt
| | - Sahar Sh Hussien
- Medical Microbiology and Immunology Department, Faculty of Medicine, Minia University, Minia, Egypt
| | - Mohammed Abdelhakeem
- Clinical Pathology Department, Faculty of Medicine, Minia University, Minia, Egypt
| | | | - Elham Ahmed
- Internal Medicine Department, Faculty of Medicine, Minia University, Minia, Egypt
| | - Soha S Abdelrahim
- Medical Microbiology and Immunology Department, Faculty of Medicine, Minia University, Minia, Egypt
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Lima de Souza Gonçalves V, Cordeiro Santos ML, Silva Luz M, Santos Marques H, de Brito BB, França da Silva FA, Souza CL, Oliveira MV, de Melo FF. From Helicobacter pylori infection to gastric cancer: Current evidence on the immune response. World J Clin Oncol 2022; 13:186-199. [PMID: 35433296 PMCID: PMC8966509 DOI: 10.5306/wjco.v13.i3.186] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 07/31/2021] [Accepted: 02/15/2022] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is the result of a multifactorial process whose main components are infection by Helicobacter pylori (H. pylori), bacterial virulence factors, host immune response and environmental factors. The development of the neoplastic microenvironment also depends on genetic and epigenetic changes in oncogenes and tumor suppressor genes, which results in deregulation of cell signaling pathways and apoptosis process. This review summarizes the main aspects of the pathogenesis of GC and the immune response involved in chronic inflammation generated by H. pylori.
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Affiliation(s)
| | - Maria Luísa Cordeiro Santos
- Universidade Federal da Bahia, Instituto Multidisciplinar em Saúde, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Marcel Silva Luz
- Universidade Federal da Bahia, Instituto Multidisciplinar em Saúde, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Hanna Santos Marques
- Universidade Estadual do Sudoeste da Bahia, Campus Vitória da Conquista, Vitória da Conquista 45083-900, Bahia, Brazil
| | - Breno Bittencourt de Brito
- Universidade Federal da Bahia, Instituto Multidisciplinar em Saúde, Vitória da Conquista 45029-094, Bahia, Brazil
| | | | - Cláudio Lima Souza
- Universidade Federal da Bahia, Instituto Multidisciplinar em Saúde, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Márcio Vasconcelos Oliveira
- Universidade Federal da Bahia, Instituto Multidisciplinar em Saúde, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Fabrício Freire de Melo
- Universidade Federal da Bahia, Instituto Multidisciplinar em Saúde, Vitória da Conquista 45029-094, Bahia, Brazil
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Xue Z, Yang H, Su D, Song X, Deng X, Yu C, Sun C, He L, You Y, Gong Y, Fan D, Sun L, Han X, Fan R, Zhang M, Yan X, Qian J, Zhang J. Geographic distribution of the cagA, vacA, iceA, oipA and dupA genes of Helicobacter pylori strains isolated in China. Gut Pathog 2021; 13:39. [PMID: 34130751 PMCID: PMC8207754 DOI: 10.1186/s13099-021-00434-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 06/07/2021] [Indexed: 02/06/2023] Open
Abstract
Background There are geographic variations in the genotypes of Helicobacter pylori (H. pylori) cagA, vacA, iceA, oipA and dupA. The aim of the study was to investigate the distribution of these genotypes among H. pylori strains from five regions of China and their association with clinical outcomes. Materials and methods Gastric biopsy specimens were obtained from 348 patients with different gastrointestinal diseases in the five regions of China. The regional distribution was 89 patients from Shandong, 91 from Guangxi, 57 from Hunan, 58 from Qinghai and 53 from Heilongjiang. The presence of cagA, vacA, iceA, oipA and dupA genotypes was determined by polymerase chain reaction (PCR) from H. pylori DNA. Results A total of 269 H. pylori isolates were obtained, of which 74 isolates were from Shandong, 78 from Guangxi, 46 from Hunan, 33 from Qinghai and 38 from Heilongjiang. The cagA-positive status was predominant in the five regions. The predominant vacA genotypes were s1c (73.4%), m2 (70.6%) and i1 (92.9%). In strains from Shandong, s1a and m1 were dominant. By contrast, s1c was dominant in Guangxi and i1 was dominant in Hunan and Heilongjiang. The prevalence of m2 subtype in Qinghai (78.8%) was significantly higher than that in other regions (P < 0.05). The predominant iceA genotype was iceA1 and the frequency of iceA1 was significantly more prevalent in Hunan than in other regions (P < 0.05). The oipA status “on” gene was more frequent in Shandong (91.9%) and Guangxi (91%) than in Heilongjiang (71.7%) (P < 0.05). Conversely, the dupA-positive status was less than half in Shandong (31.1%) and Guangxi (15.4%), whereas it was 73.9% in Hunan and 81.8% in Qinghai (P < 0.001). There were no significant associations between the cagA, vacA, iceA, oipA genotypes and clinical outcomes. The dupA-positive strains were more common in peptic ulcer disease (PUD) patients than in non-ulcer dyspepsia (NUD) patients in Shandong and Guangxi (P < 0.05), but the association was not observed in other geographic regions. Conclusions There was significant geographic diversity of H. pylori genotypes in different regions of China and the presence of dupA gene can be considered as a marker for the development of gastroduodenal diseases. However, the cagA, iceA, vacA and oipA genes cannot be regarded for prediction of the clinical presentation of H. pylori infection in China. Supplementary Information The online version contains supplementary material available at 10.1186/s13099-021-00434-4.
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Affiliation(s)
- Zhijing Xue
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, China
| | - Hong Yang
- Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Dongxing Su
- The Second Nanning People's Hospital, Nanning, Guangxi Zhuang Autonomous Region, Nanning, China
| | - Xiangfeng Song
- Department of Gastroenterology, Rushan People's Hospital, Rushan, Shandong, China
| | - Xin Deng
- Yiyang Central Hospital, Yiyang, Hunan, China
| | - Changhong Yu
- The First Affiliated Hospital of Jiamusi Medical University, Jiamusi, Heilongjiang, China
| | - Chunhua Sun
- The People's Hospital of Huzhu Tu Ethnic Autonomous County, Haidong, Qinghai, China
| | - Lihua He
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, China
| | - Yuanhai You
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, China
| | - Yanan Gong
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, China
| | - Dongjie Fan
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, China
| | - Lu Sun
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, China
| | - Xiurui Han
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, China
| | - Ruyue Fan
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, China
| | - Maojun Zhang
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, China
| | - Xiaomei Yan
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, China
| | - Jiaming Qian
- Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
| | - Jianzhong Zhang
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, China.
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de Souza MPC, de Camargo BAF, Spósito L, Fortunato GC, Carvalho GC, Marena GD, Meneguin AB, Bauab TM, Chorilli M. Highlighting the use of micro and nanoparticles based-drug delivery systems for the treatment of Helicobacter pylori infections. Crit Rev Microbiol 2021; 47:435-460. [PMID: 33725462 DOI: 10.1080/1040841x.2021.1895721] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Due to the high adaptability of Helicobacter pylori and the low targeting specificity of the drugs normally used in pharmacological therapy, the strains are becoming increasingly resistant to these drugs, making it difficult to eradicate the infection. Thus, the search for new therapeutic approaches has been considered urgent. The incorporation of drugs in advanced drug delivery systems, such as nano and microparticles, would allow the improvement of the retention time in the stomach and the prolongation of drug release rates at the target site. Because of this, the present review article aims to highlight the use of micro and nanoparticles as important technological tools for the treatment of H. pylori infections, focussing on the main nanotechnological systems, including nanostructured lipid carriers, liposomes, nanoemulsion, metallic nanoparticles, and polymeric nanoparticles, as well as microtechnological systems such as gastroretentive dosage forms, among them mucoadhesive, magnetic and floating systems were highlighted.
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Affiliation(s)
| | | | - Larissa Spósito
- School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil São Paulo
| | | | - Gabriela Corrêa Carvalho
- School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil São Paulo
| | - Gabriel Davi Marena
- School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil São Paulo
| | | | - Taís Maria Bauab
- School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil São Paulo
| | - Marlus Chorilli
- School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil São Paulo
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Soyfoo DM, Doomah YH, Xu D, Zhang C, Sang HM, Liu YY, Zhang GX, Jiang JX, Xu SF. New genotypes of Helicobacter Pylori VacA d-region identified from global strains. BMC Mol Cell Biol 2021; 22:4. [PMID: 33413074 PMCID: PMC7791883 DOI: 10.1186/s12860-020-00338-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 12/16/2020] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Pathogenesis of Helicobacter Pylori (HP) vacuolating toxin A (vacA) depends on polymorphic diversity within the signal (s), middle (m), intermediate (i), deletion (d) and c-regions. These regions show distinct allelic diversity. The s-region, m-region and the c-region (a 15 bp deletion at the 3'-end region of the p55 domain of the vacA gene) exist as 2 types (s1, s2, m1, m2, c1 and c2), while the i-region has 3 allelic types (i1, i2 and i3). The locus of d-region of the vacA gene has also been classified into 2 genotypes, namely d1 and d2. We investigated the "d-region"/"loop region" through bioinformatics, to predict its properties and relation to disease. One thousand two hundred fifty-nine strains from the NCBI nucleotide database and the dryad database with complete vacA sequences were included in the study. The sequences were aligned using BioEdit and analyzed using Lasergene and BLAST. The secondary structure and physicochemical properties of the region were predicted using PredictProtein. RESULTS We identified 31 highly polymorphic genotypes in the "d-region", with a mean length of 34 amino acids (9 ~ 55 amino acids). We further classified the 31 genotypes into 3 main types, namely K-type (strains starting with the KDKP motif in the "d-region"), Q-type (strains starting with the KNQT motif), and E-type (strains starting with the ESKT motif) respectively. The most common type, K-type, is more prevalent in cancer patients (80.87%) and is associated with the s1i1m1c1 genotypes (P < .01). Incidentally, a new region expressing sequence diversity (2 aa deletion) at the C-terminus of the p55 domain of vacA was identified during bioinformatics analysis. CONCLUSIONS Prediction of secondary structures shows that the "d-region" adopts a loop conformation and is a disordered region.
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Affiliation(s)
- Djaleel Muhammad Soyfoo
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yussriya Hanaa Doomah
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Dong Xu
- Department of Electrical Engineering and Computer Science, Bond Life Sciences Center, University of Missouri, Columbia, MO, USA
| | - Chao Zhang
- Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, 10021, USA.,Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY, 10021, USA
| | - Huai-Ming Sang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yan-Yan Liu
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Guo-Xin Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jian-Xia Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
| | - Shun-Fu Xu
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
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11
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Bakhti SZ, Latifi‐Navid S, Safaralizadeh R. Helicobacter pylori-related risk predictors of gastric cancer: The latest models, challenges, and future prospects. Cancer Med 2020; 9:4808-4822. [PMID: 32363738 PMCID: PMC7333836 DOI: 10.1002/cam4.3068] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 03/31/2020] [Accepted: 03/31/2020] [Indexed: 12/24/2022] Open
Abstract
Helicobacter pylori is known as an important determinant of preneoplastic lesions or gastric cancer (GC) risk. The bacterial genotypes may determine the clinical outcomes. However, the evidence for these associations has varied between and within continents, and the actual effect of each gene and corresponding allelic variants are still debatable. In recent years, two new models have been proposed to predict the risk of GC; the phylogeographic origin of H. pylori strains and a disrupted co-evolution between H. pylori and its human host, which potentially explain the geographic differences in the risk of H. pylori-related cancer. However, these models and earlier ones based on putative virulence factors of the bacterium may not fully justify differences in the incidence of GC, reflecting that new theories should be developed and examined. Notably, the new findings also support the role of ancestry-specific germline alteration in contributing to the ethnic/population differences in cancer risk. Moreover the high and low incidence areas of GC have shown differences in transmission ecology, largely affecting the composition of H. pylori populations. As a new hypothesis, it is proposed that any high-risk population may have its own specific risk loci (or variants) as well as new H. pylori strains with national/maybe regional gene pools that should be considered. The latter is seen in the Americas where the rapid evolution of distinct H. pylori subpopulations has been occurred. It is therefore proposed that the deep sequencing of both H. pylori and its human host is simultaneously performed in GC patients and age-sex-matched controls from high-risk areas. The expression and functional activities of the identified new determinants of GC must then be assessed and matched with human and pathogen ancestry, because some of risk loci are ancestry-specific. In addition, potential study-level covariates and moderator variables (eg physical conditions, life styles, gastric microbiome, etc) linked to causal relationships, and their impact, should be recognized and controlled.
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Affiliation(s)
- Seyedeh Zahra Bakhti
- Department of BiologyFaculty of SciencesUniversity of Mohaghegh ArdabiliArdabilIran
| | - Saeid Latifi‐Navid
- Department of BiologyFaculty of SciencesUniversity of Mohaghegh ArdabiliArdabilIran
| | - Reza Safaralizadeh
- Department of Animal BiologyFaculty of Natural SciencesUniversity of TabrizTabrizIran
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12
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Bakhti SZ, Latifi-Navid S, Zahri S. Unique constellations of five polymorphic sites of Helicobacter pylori vacA and cagA status associated with risk of gastric cancer. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2020; 79:104167. [PMID: 31891782 DOI: 10.1016/j.meegid.2019.104167] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 12/03/2019] [Accepted: 12/27/2019] [Indexed: 12/22/2022]
Abstract
Helicobacter pylori possesses virulence genes that are involved in the pathogenesis of the bacterium. There are little data regarding all constellations of five polymorphic sites of H. pylori vacA and cagA status. We therefore aimed to i) find any associations between H. pylori vacA alleles (s1/s2, m1/m2, i1/i2, d1/d2, and c1/c2) and cagA status and ii) determine the frequency of all five-genotype combinations of the vacA alleles with and without cagA gene, and their associations with risk of gastric cancer (GC). A total of 290 Iranian H. pylori isolates from gastrointestinal patients were obtained successfully by the cultivation of biopsies and genotyped. The patients included 144/290 with non-atrophic gastritis (NAG), 57/290 with peptic ulcer disease (PUD), and 89/290 with GC. We found that each of the vacA m1-, i1-, d1-, and c1-genotypes was significantly associated with cagA+ status. The odds ratio(OR) and 95% confidence interval (95% CI) was 2.316 (1.241-4.301) for cagA+/vacA m1, 2.764 (1.540-4.960) for cagA+/vacA i1, 4.288 (2.305-7.977) for cagA+/vacA d1, and 2.639 (1.488-4.680) for cagA+/vacA c1, respectively. In this study, 43 five- and six-genotype combinations were found among 224 strains. The highest frequencies were observed for vacA s1m2i2d2c2 (85/224, 37.9%), s1m2i2d2c2/cagA (48/222, 21.6%), s1m1i1d1c1 (40/224, 17.9%) and s1m1i1d1c1/cagA (35/222, 15.8%). Logistic regression analysis showed that vacA s1m1i1d1c1, s1m2i1d2c1, s1m2i2d2c1, and s1m2i2d2c1/cagA had a high prevalence in GC patients compared to non-atrophic gastritis patients (p < .05). The ORs and 95% CI were 2.433 (1.070-5.531), 11.524 (1.253-106.023), 4.200 (1.261-13.993), and 6.263 (1.494-26.256), respectively. These results were also confirmed when the controls were non-tumors (NAG/PUD). We found novel five- and six-genotype combinations associated with the risk of GC. These associations seem to be strongly dependent on the presence of c1-type of vacA. Therefore, analysis of all combined genotypes of the vacA alleles and cagA status may play a significant role in determining H. pylori-related clinical outcomes.
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Affiliation(s)
- Seyedeh Zahra Bakhti
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil 56199-11367, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil 56199-11367, Iran.
| | - Saber Zahri
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil 56199-11367, Iran
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13
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Hamidi S, Badmasti F, Sadeghpour Heravi F, Safapoor MH, Mohammad Ali Tabrizi A, Ghorbani M, Azizi O. Antibiotic resistance and clonal relatedness of Helicobacter pylori strains isolated from stomach biopsy specimens in northeast of Iran. Helicobacter 2020; 25:e12684. [PMID: 32074664 DOI: 10.1111/hel.12684] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 12/25/2019] [Accepted: 02/04/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Resistant Helicobacter pylori to commonly used antimicrobial agents are associated with severe upper gastrointestinal disorders. To provide an epidemiological picture of H pylori and characterize the resistance pattern and genetic variation of clinical isolates, stomach biopsies from patients with functional dyspepsia were evaluated in northeast of Iran. MATERIALS AND METHODS In this study, 80 patients were recruited. Finally, fifty H pylori strains were isolated from antrum and corpus biopsies by culturing on Columbia agar. All strains were identified by standard laboratory procedures. Susceptibility testing of antibiotics was performed using minimum inhibitory concentration test. Allele-specific primer (ASP)-PCR of 23S rRNA which associated with clarithromycin resistance was done among resistant strains. Moreover, cagA gene and polymorphism in vacA were detected. Random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) was applied to investigate the genetic variations among all strains. RESULTS Antibiotic resistance pattern of H pylori strains was as follows: 68% (34/50) to metronidazole, 50% (25/50) to rifampicin, 30% (15/50) to amoxicillin, 28% (14/50) to levofloxacin, 22% (11/50) to clarithromycin, and 16% (8/50) to tetracycline. Multidrug-resistant strains were observed in 19 strains (38%). ASP-PCR of 23S rRNA showed four strains had A2143G mutation, six strains had A2142G mutation, and one strain had a Wt+A2143G mutation. Amplification of virulence-associated genes revealed that cagA was present in 27 isolates (54%) and vacA in 36 isolates (72%). The most common genotype of H pylori was vacA s1am2 (40%) followed by vacA s2m2 (14%), vacA s1am1 (12%), vacA s1bm1 (4%), and vacA s1bm2 (2%). DNA fingerprinting pattern indicated a high heterogeneity among isolated strains. CONCLUSION An alarming level of resistance to metronidazole and rifampicin and high heterogeneity among H pylori isolates highlighted the importance of continued monitoring of antimicrobial susceptibility and epidemiological surveillance of this pathogen.
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Affiliation(s)
- Sara Hamidi
- Department of Laboratory Sciences, School of Paramedical Sciences, Torbat Heydariyeh University of Medical sciences, Torbat Heydariyeh, Iran
| | - Farzad Badmasti
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
| | - Fatemah Sadeghpour Heravi
- Surgical Infection Research Group, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia
| | - Mohammed Hossein Safapoor
- Department of Internal Medicine, 9 Dey Educational Hospital, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran
| | - Amir Mohammad Ali Tabrizi
- Department of Laboratory Sciences, School of Paramedical Sciences, Torbat Heydariyeh University of Medical sciences, Torbat Heydariyeh, Iran
| | - Mohammad Ghorbani
- Department of Public Health, School of Health, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran
| | - Omid Azizi
- Department of Laboratory Sciences, School of Paramedical Sciences, Torbat Heydariyeh University of Medical sciences, Torbat Heydariyeh, Iran.,Health Sciences Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran
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14
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Miernyk KM, Bruden D, Rudolph KM, Hurlburt DA, Sacco F, McMahon BJ, Bruce MG. Presence of cagPAI genes and characterization of vacA s, i and m regions in Helicobacter pylori isolated from Alaskans and their association with clinical pathologies. J Med Microbiol 2020; 69:218-227. [PMID: 32011229 PMCID: PMC10874806 DOI: 10.1099/jmm.0.001123] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Introduction. Gastric cancer is a health disparity in the Alaska Native people. The incidence of Helicobacter pylori infection, a risk factor for non-cardia gastric adenocarcinoma, is also high. Gastric cancer is partially associated with the virulence of the infecting strain.Aim. To genotype the vacA s, m and i and cag pathogenicity island (cagPAI) genes in H. pylori from Alaskans and investigate associations with gastropathy.Methodology. We enrolled patients with gastritis, peptic ulcer disease (PUD) and intestinal metaplasia (IM) in 1998-2005 and patients with gastric cancer in 2011-2013. Gastric biopsies were collected and cultured and PCR was performed to detect the presence of the right and left ends of the cagPAI, the cagA, cagE, cagT and virD4 genes and to genotype the vacA s, m and i regions.Results. We recruited 263 people; 22 (8 %) had no/mild gastritis, 121 (46 %) had moderate gastritis, 40 (15%) had severe gastritis, 38 (14 %) had PUD, 30 (11 %) had IM and 12 (5 %) had gastric cancer. H. pylori isolates from 150 (57%) people had an intact cagPAI; those were associated with a more severe gastropathy (P≤0.02 for all comparisons). H. pylori isolates from 77 % of people had either the vacA s1/i1/m1 (40 %; 94/234) or s2/i2/m2 (37 %; 86/234) genotype. vacA s1/i1/m1 was associated with a more severe gastropathy (P≤0.03 for all comparisons).Conclusions. In this population with high rates of gastric cancer, we found that just over half of the H. pylori contained an intact cagPAI and 40 % had the vacA s1/i1/m1 genotype. Infection with these strains was associated with a more severe gastropathy.
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Affiliation(s)
- Karen M. Miernyk
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, AK, USA
| | - Dana Bruden
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, AK, USA
| | - Karen M. Rudolph
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, AK, USA
| | - Debby A. Hurlburt
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, AK, USA
| | - Frank Sacco
- Alaska Native Tribal Health Consortium, Anchorage, AK, USA
| | | | - Michael G. Bruce
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, AK, USA
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15
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Šterbenc A, Jarc E, Poljak M, Homan M. Helicobacter pylori virulence genes. World J Gastroenterol 2019; 25:4870-4884. [PMID: 31543679 PMCID: PMC6737321 DOI: 10.3748/wjg.v25.i33.4870] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 07/29/2019] [Accepted: 08/07/2019] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is one of the most important human pathogens, infecting approximately half of the global population. Despite its high prevalence, only a subset of H. pylori infected individuals develop serious gastroduodenal pathology. The pathogenesis of H. pylori infection and disease outcome is thus thought to be mediated by an intricate interplay between host, environmental and bacterial virulence factors. H. pylori has adapted to the harsh milieu of the human stomach through possession of various virulence genes that enable survival of the bacteria in the acidic environment, movement towards the gastric epithelium, and attachment to gastric epithelial cells. These virulence factors enable successful colonization of the gastric mucosa and sustain persistent H. pylori infection, causing chronic inflammation and tissue damage, which may eventually lead to the development of peptic ulcers and gastric cancer. Numerous studies have focused on the prevalence and role of putative H. pylori virulence genes in disease pathogenesis. While several virulence factors with various functions have been identified, disease associations appear to be less evident, especially among different study populations. This review presents key findings on the most important H. pylori virulence genes, including several bacterial adhesins and toxins, in children and adults, and focuses on their prevalence, clinical significance and potential relationships.
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Affiliation(s)
- Anja Šterbenc
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Erika Jarc
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Mario Poljak
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Matjaž Homan
- Department of Gastroenterology, Hepatology and Nutrition, University Children’s Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
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16
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Amin M, Shayesteh AA, Serajian A. Concurrent detection of cagA, vacA, sodB and hsp60 virulence genes and their relationship with clinical outcomes of disease in Helicobacter pylori isolated strains of southwest of Iran. IRANIAN JOURNAL OF MICROBIOLOGY 2019; 11:198-205. [PMID: 31523402 PMCID: PMC6711871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
BACKGROUND AND OBJECTIVES Helicobacter pylori is a Gram-negative spiral-shaped bacterium that contaminates more than half of the world's inhabitants, and infection with this bacterium is associated with some gastric disorders. Also, 5% to 10% of H. pylori genes are specific to this bacterium and many bacterial virulence factors fall into this group. The cagA, vacA, sodB and hsp60 are among important virulence factors of H. pylori. MATERIALS AND METHODS A gastric biopsy specimen was taken from 341 gastric patients and cultivated on a Colombia agar plate, containing various antibiotics, such as vancomycin, amphotericin B, and trimethoprim & polymyxin B, and incubated for 3 to 10 days under microaerophilic conditions at 37°C. PCR was used to detect the ureC, cagA, vacA, sodB and hsp60 genes. RESULTS In this study, 131 isolates were identified as H. pylori. The prevalence of cagA, vacA, sodB and hsp60 were 74%, 100%, 92.4% and 96.2%, respectively. The correlation between the clinical forms of the disease and the virulence genes were analyzed by statistical tests and no significant correlation was found. CONCLUSION The obtained results are similar to some studies conducted in different parts of the world and is different in other cases. This discrepancy is due to the difference in the type of gastric disorders, sample size and methodology.
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Affiliation(s)
- Mansour Amin
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ali Akbar Shayesteh
- Research Center for Infectious Diseases of Digestive System, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Amirarsalan Serajian
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran,Corresponding author: Amirarsalan Serajian, Ph.D, Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Tel: +986133330074, Fax: +986133720160,
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17
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Chen LL, Cui HF, Fan SF, Li ZY, Han SY, Ma X, Luo SW, Song X, Lv QY. Detection of Helicobacter pylori in dental plaque using a DNA biosensor for noninvasive diagnosis. RSC Adv 2018; 8:21075-21083. [PMID: 35539942 PMCID: PMC9080877 DOI: 10.1039/c8ra03134g] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Accepted: 06/02/2018] [Indexed: 01/08/2023] Open
Abstract
H. pylori in dental plaque was detected with a DNA biosensor with results correlating well with the 13C urea breath test.
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Affiliation(s)
- Li-Li Chen
- Department of Bioengineering
- School of Life Sciences
- Zhengzhou University
- Zhengzhou
- P. R. China
| | - Hui-Fang Cui
- Department of Bioengineering
- School of Life Sciences
- Zhengzhou University
- Zhengzhou
- P. R. China
| | - Shuang-Fei Fan
- Department of Bioengineering
- School of Life Sciences
- Zhengzhou University
- Zhengzhou
- P. R. China
| | - Zong-Yi Li
- Department of Bioengineering
- School of Life Sciences
- Zhengzhou University
- Zhengzhou
- P. R. China
| | - Shuang-Yin Han
- Division of Gastroenterology
- Henan Provincial People's Hospital
- Zhengzhou
- P. R. China
| | - Xin Ma
- Division of Stomatology
- Henan Provincial People's Hospital
- Zhengzhou
- P. R. China
| | - Shu-Wen Luo
- Division of Stomatology
- Henan Provincial People's Hospital
- Zhengzhou
- P. R. China
| | - Xiaojie Song
- Department of Bioengineering
- School of Life Sciences
- Zhengzhou University
- Zhengzhou
- P. R. China
| | - Qi-Yan Lv
- Department of Bioengineering
- School of Life Sciences
- Zhengzhou University
- Zhengzhou
- P. R. China
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18
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McClain MS, Beckett AC, Cover TL. Helicobacter pylori Vacuolating Toxin and Gastric Cancer. Toxins (Basel) 2017; 9:toxins9100316. [PMID: 29023421 PMCID: PMC5666363 DOI: 10.3390/toxins9100316] [Citation(s) in RCA: 97] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 10/03/2017] [Accepted: 10/05/2017] [Indexed: 12/13/2022] Open
Abstract
Helicobacter pylori VacA is a channel-forming toxin unrelated to other known bacterial toxins. Most H. pylori strains contain a vacA gene, but there is marked variation among strains in VacA toxin activity. This variation is attributable to strain-specific variations in VacA amino acid sequences, as well as variations in the levels of VacA transcription and secretion. In this review, we discuss epidemiologic studies showing an association between specific vacA allelic types and gastric cancer, as well as studies that have used animal models to investigate VacA activities relevant to gastric cancer. We also discuss the mechanisms by which VacA-induced cellular alterations may contribute to the pathogenesis of gastric cancer.
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Affiliation(s)
- Mark S McClain
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
| | - Amber C Beckett
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
| | - Timothy L Cover
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37212, USA.
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19
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Abdi E, Latifi-Navid S, Zahri S, Yazdanbod A, Safaralizadeh R. Helicobacter pylori genotypes determine risk of non-cardia gastric cancer and intestinal- or diffuse-type GC in Ardabil: A very high-risk area in Northwestern Iran. Microb Pathog 2017; 107:287-292. [PMID: 28390977 DOI: 10.1016/j.micpath.2017.04.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2016] [Revised: 04/03/2017] [Accepted: 04/04/2017] [Indexed: 12/16/2022]
Abstract
Frequency of the Helicobacter pylori vacA gene polymorphism and its association with gastric cancer (GC) was assessed in Ardabil, a very high-risk area in Northwestern Iran. We determined the presence of the H. pylori 16S rDNA gene and the vacA s-, m-, i-, and d-region genotypes in DNA from fresh gastric biopsies. Patients with GC were classified based on both the anatomic site and the histopathologic type of tumor Of 135 patients, including 57 with non-atrophic gastritis (NAG) and 78 with GC, 103 were infected by H. pylori. The vacA i1 and d1 genotypes were significantly linked to an increased risk of GC, where both cardia (CGC) and non-cardia GC (NCGC) patients were entered into the analysis. The adjusted OR was 9.59 for i1 and 4.39 for d1. Furthermore, i1 was significantly linked to an increased risk of the intestinal-type adenocarcinoma (OR = 14.04) and d1 to the risk of the diffuse-type adenocarcinoma (OR = 7.71). The presence of the m1-type of vacA in combination with i1 or d1 further increased the risk of GC. When the analysis was restricted to NCGC, the adjusted OR for i1 and d1, was 37.52 and 7.17, respectively. No significant association was found between genotypes and the risk of GC in the cardia site of the stomach. It is proposed that the new types of H. pylori vacA, i1 and d1, might be important determinants of NCGC risk in Ardabil. The m1, not independently, but in combination might further define the risk of GC. i1and d1 might also predict the risk of the intestinal- and diffuse-type adenocarcinomas, respectively.
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Affiliation(s)
- Esmat Abdi
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, 56199-11367, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, 56199-11367, Iran; Biosciences and Biotechnology Research Center (BBRC), Faculty of Advanced Technologies, University of Mohaghegh Ardabili, Namin, 56318-51167, Iran.
| | - Saber Zahri
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, 56199-11367, Iran
| | - Abbas Yazdanbod
- Gastrointestinal Cancer Research Center, Ardabil University of Medical Sciences, Ardabil, 56189-53141, Iran
| | - Reza Safaralizadeh
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
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El Khadir M, Alaoui Boukhris S, Benajah DA, El Rhazi K, Ibrahimi SA, El Abkari M, Harmouch T, Nejjari C, Mahmoud M, Benlemlih M, Bennani B. VacA and CagA Status as Biomarker of Two Opposite End Outcomes of Helicobacter pylori Infection (Gastric Cancer and Duodenal Ulcer) in a Moroccan Population. PLoS One 2017; 12:e0170616. [PMID: 28125638 PMCID: PMC5268467 DOI: 10.1371/journal.pone.0170616] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Accepted: 01/06/2017] [Indexed: 12/13/2022] Open
Abstract
Helicobacter pylori (H. pylori) infection induces inflammation of the gastric mucosa, which may progress to precancerous lesions leading to gastric cancer. Pathological determinism is associated to some virulence genes of the bacterium, notably the vacA and cagA genes. The present study aimed to determine the H. pylori genotypes distribution and their association with sex, age and gastric diseases in a Moroccan population. Gastric biopsy was taken from 1079 consenting patients. The specimens were processed by PCR to identify H. pylori and to determine the genotypic profile by PCR characterizing vacA s, vacA m and vacA i regions directly from biopsies H. pylori positives. VacA genotyping revealed the predominance of vacA m2 (53.2%), vacA s2 (52.9%) and vacA i2 (52%). The most virulent vacA alleles (s1, i1 and m1) are more predominant in men (47.3%, 41.9% and 46.1% respectively) than in women (38.3%, 33.3% and 37% respectively). However, the association between vacA genotypes and age did not reach a statistical significant value. Logistic regression analysis results show that vacA i1m1 and vacA i1m2 genotypes were strongly associated with the risk of GC, the Odds Ratio (95% confidence interval) was 29.73 [5.08-173.73] and 9.17 [2.06-40.82] respectively, while vacAs1/cagA+ seems to be a risk factor for DU since it is inversely associated with GC (OR was 0.13 [0.02-0.75]. The results of this study suggest that vacA i1 genotype independently to vacAm status may be of a clinical usefulness and will help to identify patients at a high risk of GC development.
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Affiliation(s)
- Mounia El Khadir
- Laboratoire de Microbiologie et de Biologie Moléculaire, Equipe Micro-organismes, Génomique et Facteurs Oncogènes, Faculté de Médecine et de Pharmacie de Fès (FMPF), Université Sidi Mohammed Ben Abdellah (USMBA), Fez, Morocco
- Laboratoire de Biotechnologie, Faculté des Sciences Dhar El Mehraz, USMBA, Fez, Morocco
| | - Samia Alaoui Boukhris
- Laboratoire de Microbiologie et de Biologie Moléculaire, Equipe Micro-organismes, Génomique et Facteurs Oncogènes, Faculté de Médecine et de Pharmacie de Fès (FMPF), Université Sidi Mohammed Ben Abdellah (USMBA), Fez, Morocco
| | - Dafr-Allah Benajah
- Service d’Hépato Gastro-entérologie, CHU Hassan II de Fès, Equipe Maladies de l’Appareil Digestif, FMPF, Fez, Morocco
- Laboratoire de Pathologie Humaine, Biomédecine et Environnement, FMPF, USMBA, Fez, Morocco
| | - Karima El Rhazi
- Laboratoire d’Epidémiologie et de Recherche Clinique, FMPF, USMBA, Fez, Morocco
| | - Sidi Adil Ibrahimi
- Service d’Hépato Gastro-entérologie, CHU Hassan II de Fès, Equipe Maladies de l’Appareil Digestif, FMPF, Fez, Morocco
- Laboratoire de Pathologie Humaine, Biomédecine et Environnement, FMPF, USMBA, Fez, Morocco
| | - Mohamed El Abkari
- Service d’Hépato Gastro-entérologie, CHU Hassan II de Fès, Equipe Maladies de l’Appareil Digestif, FMPF, Fez, Morocco
- Laboratoire de Pathologie Humaine, Biomédecine et Environnement, FMPF, USMBA, Fez, Morocco
| | | | - Chakib Nejjari
- Laboratoire d’Epidémiologie et de Recherche Clinique, FMPF, USMBA, Fez, Morocco
| | | | - Mohamed Benlemlih
- Laboratoire de Biotechnologie, Faculté des Sciences Dhar El Mehraz, USMBA, Fez, Morocco
| | - Bahia Bennani
- Laboratoire de Microbiologie et de Biologie Moléculaire, Equipe Micro-organismes, Génomique et Facteurs Oncogènes, Faculté de Médecine et de Pharmacie de Fès (FMPF), Université Sidi Mohammed Ben Abdellah (USMBA), Fez, Morocco
- Laboratoire de Pathologie Humaine, Biomédecine et Environnement, FMPF, USMBA, Fez, Morocco
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Bakhti SZ, Latifi-Navid S, Mohammadi S, Zahri S, Bakhti FS, Feizi F, Yazdanbod A, Siavoshi F. Relevance of Helicobacter pylori vacA 3'-end Region Polymorphism to Gastric Cancer. Helicobacter 2016; 21:305-16. [PMID: 26612250 DOI: 10.1111/hel.12284] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND Helicobacter pylori vacA genotypes play an important role in the pathogenesis of severe gastrointestinal disease. MATERIALS AND METHODS We identified a novel polymorphic site in the 3'-end region of H. pylori vacA gene, denoted by c1/-c2 (c1: with deletion of 15 bp), and examined associations of this and the previous four sites as well as cagA status with gastroduodenal diseases, in a total of 217 Iranian H. pylori isolates. Histopathologic evaluations were performed and patients with gastric cancer (GC) were further classified based on the anatomic site of tumor, including cardia and noncardia GC, and the histopathologic type of tumor, including intestinal- and diffuse-type GC. RESULTS The vacA m1, i1, d1, c1, and cagA genotypes were significantly associated with an increased risk of GC, the odds ratio (95% confidence interval) was 4.29 (2.03-9.08), 6.11 (2.63-14.19), 3.18 (1.49-6.76), 15.13 (5.86-39.01), and 2.59 (1.09-6.12), respectively. The vacA c1 genotype had an increased age- and sex-adjusted risk for GC by the multiple logistic regression analysis; the OR was 38.32 (95% CI, 6.60-222.29). This association was independent of and larger than the associations of the m-, i-, and d-type of vacA or cagA status with GC. No significant correlation was found between s1, whether independently or in combination, and the risk of GC or peptic ulcer disease (PUD). The vacA i1 and cagA genotypes were linked to an increased risk of PUD; the OR (95% CI) was 2.80 (1.45-5.40) and 2.62 (1.23-5.61), respectively. The presence of both the vacA i1 and cagA genotypes further increased the risk of PUD; the OR was 5.20 (95% CI, 1.92-14.03). CONCLUSION The H. pylori vacA c1 genotype might therefore be one of the strongest risk predictors of GC in male patients aged ≥55 in Iran.
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Affiliation(s)
- Seyedeh Zahra Bakhti
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Shiva Mohammadi
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Saber Zahri
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Fatemeh Sadat Bakhti
- Department of Biostatistics, Faculty of Public Health, Mazandaran University of Medical Sciences, Sari, Iran
| | - Farideh Feizi
- Aras Clinics, Imam Khomeini Hospital, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Abbas Yazdanbod
- Gastrointestinal Cancer Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Farideh Siavoshi
- Department of Microbiology, School of Biology, University College of Sciences, University of Tehran, Tehran, Iran
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22
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Thi Huyen Trang T, Thanh Binh T, Yamaoka Y. Relationship between vacA Types and Development of Gastroduodenal Diseases. Toxins (Basel) 2016; 8:toxins8060182. [PMID: 27294955 PMCID: PMC4926148 DOI: 10.3390/toxins8060182] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 05/29/2016] [Accepted: 05/31/2016] [Indexed: 02/07/2023] Open
Abstract
The Helicobacter pylori vacuolating cytotoxin (VacA) is a secreted pore-forming toxin and a major virulence factor in the pathogenesis of H. pylori infection. While VacA is present in almost all strains, only some forms are toxigenic and pathogenic. While vacA and its genotypes are considered as markers of H. pylori-related diseases or disorders, the pathophysiological mechanisms of VacA and its genotypes remain controversial. This review outlines key findings of publications regarding vacA with emphasis on the relationship between vacA genotypes and the development of human disease.
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Affiliation(s)
- Tran Thi Huyen Trang
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu-City, Oita 879-5593, Japan.
- Department of Molecular Biology, 108 Hospital, Hanoi, Vietnam.
| | - Tran Thanh Binh
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu-City, Oita 879-5593, Japan.
- Department of Endoscopy, Cho Ray Hospital, Ho Chi Minh, Vietnam.
| | - 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, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX 77030, USA.
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Helicobacter pylori vacA Genotypes in Chronic Gastritis and Gastric Carcinoma Patients from Macau, China. Toxins (Basel) 2016; 8:toxins8050142. [PMID: 27164143 PMCID: PMC4885057 DOI: 10.3390/toxins8050142] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2016] [Revised: 04/11/2016] [Accepted: 04/29/2016] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori is the major triggering factor for gastric carcinoma, but only a small proportion of infected patients develop this disease. Differences in virulence observed among H. pylori strains, namely in the vacuolating cytotoxin vacA gene, may contribute to this discrepancy. Infection with vacA s1, i1 and m1 strains increases the risk for progression of gastric premalignant lesions and for gastric carcinoma. However, in East Asian countries most of the H. pylori strains are vacA s1, regardless of the patients’ clinical status, and the significance of the vacA i1 and m1 genotypes for gastric carcinoma in this geographic area remains to be fully elucidated. The aim of the present study was to investigate this relationship in 290 patients from Macau, China. Using very sensitive and accurate genotyping methods, we detected infection with vacA i1 and with vacA m1 strains in, respectively, 85.2% and 52.6% of the patients that were infected with single genotypes. The prevalence of cagA-positive strains was 87.5%. No significant associations were observed between vacA genotypes or cagA and gastric carcinoma. It is worth noting that 37.5% of the infected patients had coexistence of H. pylori strains with different vacA genotypes. Additional studies directed to other H. pylori virulence factors should be performed to identify high risk patients in East Asia.
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Liu X, He B, Cho WC, Pan Y, Chen J, Ying H, Wang F, Lin K, Peng H, Wang S. A systematic review on the association between the Helicobacter pylori vacA i genotype and gastric disease. FEBS Open Bio 2016; 6:409-417. [PMID: 27419046 PMCID: PMC4856419 DOI: 10.1002/2211-5463.12046] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Revised: 01/20/2016] [Accepted: 02/16/2016] [Indexed: 12/16/2022] Open
Abstract
Helicobacter pylori (H. pylori) has been recognized as a cause of gastrointestinal diseases and progress of the pathology of gastrointestinal diseases is related to the genotype of H. pylori. Published studies have indicated that the H. pylori vacuolating cytotoxin gene A (vacA) i1/i2 genotype is associated with peptic ulcer disease (PUD) and gastric cancer (GC), but their conclusions are inconsistent. This study aimed to further assess the risk of vacA i gene for PUD and/or GC. A systematic search was conducted across three main electronic databases (PubMed, Web of Science, and CNKI). A meta-analysis was then performed on the pooled data of the published articles to estimate the overall influence of vacA i polymorphisms on PUD and/or GC by crude odds ratio (OR) with 95% confidence intervals (CI). The reliability of the results were confirmed by publication bias and sensitivity analysis of included studies. A total of 14 studies were selected according to the specific inclusion and exclusion criteria. The pooled results revealed that patients with GC were more vulnerable to infection by H. pylori i1 genotype (OR = 5.12; 95% CI: 2.66-9.85; P < 0.001) than those with chronic gastritis or nonulcer disease. Moreover, the results of subgroup analysis indicated that the i1 genotype of H. pylori was associated with an increased GC risk (OR = 10.89; 95% CI: 4.11-20.88; P < 0.001) in the Middle Asian population. The H. pylori vacA i1 genotype is associated with an increased GC risk, especially in the Middle Asian population.
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Affiliation(s)
- Xian Liu
- Central Laboratory Nanjing First Hospital Nanjing Medical University Jiangsu China
| | - Bangshun He
- Central Laboratory Nanjing First Hospital Nanjing Medical University Jiangsu China
| | - William C Cho
- Department of Clinical Oncology Queen Elizabeth Hospital Hong Kong China
| | - Yuqin Pan
- Central Laboratory Nanjing First Hospital Nanjing Medical University Jiangsu China
| | - Jie Chen
- Department of Life Sciences Nanjing Normal University Jiangsu China
| | - Houqun Ying
- Medical College Southeast University Nanjing Jiangsu China
| | - Feng Wang
- Central Laboratory Nanjing First Hospital Nanjing Medical University Jiangsu China
| | - Kang Lin
- Central Laboratory Nanjing First Hospital Nanjing Medical University Jiangsu China
| | - Hongxin Peng
- Medical College Southeast University Nanjing Jiangsu China
| | - Shukui Wang
- Central Laboratory Nanjing First Hospital Nanjing Medical University Jiangsu China
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Raei N, Behrouz B, Zahri S, Latifi-Navid S. Helicobacter pylori Infection and Dietary Factors Act Synergistically to Promote Gastric Cancer. Asian Pac J Cancer Prev 2016; 17:917-21. [DOI: 10.7314/apjcp.2016.17.3.917] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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26
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Kao CY, Sheu BS, Wu JJ. Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis. Biomed J 2016; 39:14-23. [PMID: 27105595 PMCID: PMC6138426 DOI: 10.1016/j.bj.2015.06.002] [Citation(s) in RCA: 290] [Impact Index Per Article: 32.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Accepted: 06/08/2015] [Indexed: 12/16/2022] Open
Abstract
Helicobacter pylori pathogenesis and disease outcomes are mediated by a complex interplay between bacterial virulence factors, host, and environmental factors. After H. pylori enters the host stomach, four steps are critical for bacteria to establish successful colonization, persistent infection, and disease pathogenesis: (1) Survival in the acidic stomach; (2) movement toward epithelium cells by flagella-mediated motility; (3) attachment to host cells by adhesins/receptors interaction; (4) causing tissue damage by toxin release. Over the past 20 years, the understanding of H. pylori pathogenesis has been improved by studies focusing on the host and bacterial factors through epidemiology researches and molecular mechanism investigations. These include studies identifying the roles of novel virulence factors and their association with different disease outcomes, especially the bacterial adhesins, cag pathogenicity island, and vacuolating cytotoxin. Recently, the development of large-scale screening methods, including proteomic, and transcriptomic tools, has been used to determine the complex gene regulatory networks in H. pylori. In addition, a more available complete genomic database of H. pylori strains isolated from patients with different gastrointestinal diseases worldwide is helpful to characterize this bacterium. This review highlights the key findings of H. pylori virulence factors reported over the past 20 years.
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Affiliation(s)
- Cheng-Yen Kao
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Bor-Shyang Sheu
- Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Jiunn-Jong Wu
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan; Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan.
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27
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Zabaglia LM, Ferraz MA, Pereira WN, Orcini WA, de Labio RW, Neto AC, Wisnieski F, de Oliveira JG, de Arruda Cardoso Smith M, Payão SLM, Rasmussen LT. Lack of association among TNF-α gene expression, -308 polymorphism (G > A) and virulence markers of Helicobacter pylori. J Venom Anim Toxins Incl Trop Dis 2015; 21:54. [PMID: 26719751 PMCID: PMC4696262 DOI: 10.1186/s40409-015-0054-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Accepted: 12/21/2015] [Indexed: 12/18/2022] Open
Abstract
Background Tumor necrosis factor plays a critical role in the pathogenesis of gastric diseases such as gastric cancer, and an abnormal inflammatory response has frequently been observed in dyspeptic patients. Helicobacter pylori infection can induce a gastric mucosal inflammatory response that may be influenced by -308 (G > A) polymorphisms and gene expression of the TNF-α gene. Methods One hundred and thirty-four gastric biopsy samples were collected from patients of both genders (61♂ and 73♀, mean age 40.3 ± 24.2 years) with gastric symptoms. The -308 (G > A) polymorphism of TNF-α was characterized using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The expression level was measured using real-time PCR, and relative quantification (RQ) was calculated using the comparative CT method (2-ΔΔCT). Results The analysis revealed an increase in TNF-α gene expression in patients with gastritis; on the other hand, no statistical differences were observed in patients with gastric cancer. In addition, no association was found among -308 polymorphism genotypes, virulence markers, or TNF-α gene expression. Conclusions Helicobacter pylori induces a large increase in TNF-α expression in patients with gastritis, regardless of tissue inflammation, but after the tissue becomes neoplastic, the presence of bacteria did not influence expression. These results suggest that the TNF-α pathway may play an important role in the progression from gastritis to gastric cancer
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Affiliation(s)
- Luanna Munhoz Zabaglia
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil
| | - Mariane Avante Ferraz
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil
| | - Weendelly Nayara Pereira
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil
| | - Wilson Aparecido Orcini
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil
| | | | | | - Fernanda Wisnieski
- Universidade Federal de São Paulo, Rua Sena Madureira, 1500, 04021-001 São Paulo, SP Brazil
| | | | | | - Spencer Luiz Marques Payão
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil ; Faculdade de Medicina de Marília, Rua Lourival Freire 240, 17519-050 Marília, SP Brazil
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Ahn HJ, Lee DS. Helicobacter pylori in gastric carcinogenesis. World J Gastrointest Oncol 2015; 7:455-65. [PMID: 26690981 PMCID: PMC4678392 DOI: 10.4251/wjgo.v7.i12.455] [Citation(s) in RCA: 73] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2015] [Revised: 10/10/2015] [Accepted: 11/03/2015] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer still is a major concern as the third most common cancer worldwide, despite declining rates of incidence in many Western countries. Helicobacter pylori (H. pylori) is the major cause of gastric carcinogenesis, and its infection insults gastric mucosa leading to the occurrence of atrophic gastritis which progress to intestinal metaplasia, dysplasia, early gastric cancer, and advanced gastric cancer consequently. This review focuses on multiple factors including microbial virulence factors, host genetic factors, and environmental factors, which can heighten the chance of occurrence of gastric adenocarcinoma due to H. pylori infection. Bacterial virulence factors are key components in controlling the immune response associated with the induction of carcinogenesis, and cagA and vacA are the most well-known pathogenic factors. Host genetic polymorphisms contribute to regulating the inflammatory response to H. pylori and will become increasingly important with advancing techniques. Environmental factors such as high salt and smoking may also play a role in gastric carcinogenesis. It is important to understand the virulence factors, host genetic factors, and environmental factors interacting in the multistep process of gastric carcinogenesis. To conclude, prevention via H. pylori eradication and controlling environmental factors such as diet, smoking, and alcohol is an important strategy to avoid H. pylori-associated gastric carcinogenesis.
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29
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Histological variety of gastric carcinoma and Helicobacter pylori cagA and vacA polymorphism. Eur J Gastroenterol Hepatol 2015; 27:1017-21. [PMID: 26067222 DOI: 10.1097/meg.0000000000000414] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Helicobacter pylori infection may increase the risk of both histotypes of gastric carcinoma (GC): intestinal (IGC) and diffuse (DGC). Polymorphism of the main H. pylori virulence factors, cagA and vacA, could have a different impact on the histological variety of GC. METHODS Two hundred and twenty-six H. pylori colonies were examined from 28 GC patients: 15 with IGC and 13 with DGC. DNA was extracted from bacteria and a PCR was performed using primers specific for cagA, the 3' cagA variable region and s and m regions of vacA. RESULTS There were 214 cagA+ strains and 55.61% of them were isolated from IGC cases; there were 12 cagA- colonies and they were all isolated from DGC (P<0.001). Most patients were infected by strains with more than one cagA structural type. No strains with a particular cagA type were found to be significantly more frequent in either histological variety of GC. A percentage of 43.90 of strains with vacA subtype s1/m1 were isolated from IGC, whereas 80.95% of vacA subtype s1/m2 strains were isolated from DGC cases (P<0.001). CONCLUSION Polymorphism of the main virulence genes of H. pylori may play different roles in the pathogenesis of IGC and DGC.
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30
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Magalhães A, Marcos-Pinto R, Nairn AV, Dela Rosa M, Ferreira RM, Junqueira-Neto S, Freitas D, Gomes J, Oliveira P, Santos MR, Marcos NT, Xiaogang W, Figueiredo C, Oliveira C, Dinis-Ribeiro M, Carneiro F, Moremen KW, David L, Reis CA. Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways. Biochim Biophys Acta Mol Basis Dis 2015; 1852:1928-39. [PMID: 26144047 DOI: 10.1016/j.bbadis.2015.07.001] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2015] [Revised: 05/29/2015] [Accepted: 07/01/2015] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori exploits host glycoconjugates to colonize the gastric niche. Infection can persist for decades promoting chronic inflammation, and in a subset of individuals lesions can silently progress to cancer. This study shows that H. pylori chronic infection and gastric tissue inflammation result in a remodeling of the gastric glycophenotype with increased expression of sialyl-Lewis a/x antigens due to transcriptional up-regulation of the B3GNT5, B3GALT5, and FUT3 genes. We observed that H. pylori infected individuals present a marked gastric local pro-inflammatory signature with significantly higher TNF-α levels and demonstrated that TNF-induced activation of the NF-kappaB pathway results in B3GNT5 transcriptional up-regulation. Furthermore, we show that this gastric glycosylation shift, characterized by increased sialylation patterns, favors SabA-mediated H. pylori attachment to human inflamed gastric mucosa. This study provides novel clinically relevant insights into the regulatory mechanisms underlying H. pylori modulation of host glycosylation machinery, and phenotypic alterations crucial for life-long infection. Moreover, the biosynthetic pathways here identified as responsible for gastric mucosa increased sialylation, in response to H. pylori infection, can be exploited as drug targets for hindering bacteria adhesion and counteract the infection chronicity.
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Affiliation(s)
- Ana Magalhães
- Institute for Research and Innovation in Health (i3S), University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal
| | - Ricardo Marcos-Pinto
- Centro Hospitalar do Porto (CHP), Gastroenterology Department, Portugal; Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Portugal; Medical Faculty, University of Porto, Portugal
| | - Alison V Nairn
- Complex Carbohydrate Research Center and Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA
| | - Mitche Dela Rosa
- Complex Carbohydrate Research Center and Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA
| | - Rui M Ferreira
- Institute for Research and Innovation in Health (i3S), University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal
| | - Susana Junqueira-Neto
- Institute for Research and Innovation in Health (i3S), University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal
| | - Daniela Freitas
- Institute for Research and Innovation in Health (i3S), University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal
| | - Joana Gomes
- Institute for Research and Innovation in Health (i3S), University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal
| | - Patrícia Oliveira
- Institute for Research and Innovation in Health (i3S), University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal
| | - Marta R Santos
- Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal
| | - Nuno T Marcos
- Institute for Research and Innovation in Health (i3S), University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal; Section of Health Sciences, University of Aveiro, Portugal
| | - Wen Xiaogang
- Department of Pathology, Centro Hospitalar São João, Porto, Portugal; Centro Hospitalar Vila Nova de Gaia/Espinho, Portugal
| | - Céu Figueiredo
- Institute for Research and Innovation in Health (i3S), University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal; Medical Faculty, University of Porto, Portugal
| | - Carla Oliveira
- Institute for Research and Innovation in Health (i3S), University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal; Medical Faculty, University of Porto, Portugal
| | - Mário Dinis-Ribeiro
- Medical Faculty, University of Porto, Portugal; Gastroenterology Department, IPO Porto, Portugal; CIDES/CINTESIS, University of Porto, Portugal
| | - Fátima Carneiro
- Institute for Research and Innovation in Health (i3S), University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal; Medical Faculty, University of Porto, Portugal; Department of Pathology, Centro Hospitalar São João, Porto, Portugal
| | - Kelley W Moremen
- Complex Carbohydrate Research Center and Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA
| | - Leonor David
- Institute for Research and Innovation in Health (i3S), University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal; Medical Faculty, University of Porto, Portugal
| | - Celso A Reis
- Institute for Research and Innovation in Health (i3S), University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal; Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Portugal; Medical Faculty, University of Porto, Portugal.
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Fontenete S, Leite M, Guimarães N, Madureira P, Ferreira RM, Figueiredo C, Wengel J, Azevedo NF. Towards Fluorescence In Vivo Hybridization (FIVH) Detection of H. pylori in Gastric Mucosa Using Advanced LNA Probes. PLoS One 2015; 10:e0125494. [PMID: 25915865 PMCID: PMC4410960 DOI: 10.1371/journal.pone.0125494] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2014] [Accepted: 03/12/2015] [Indexed: 12/13/2022] Open
Abstract
In recent years, there have been several attempts to improve the diagnosis of infection caused by Helicobacter pylori. Fluorescence in situ hybridization (FISH) is a commonly used technique to detect H. pylori infection but it requires biopsies from the stomach. Thus, the development of an in vivo FISH-based method (FIVH) that directly detects and allows the visualization of the bacterium within the human body would significantly reduce the time of analysis, allowing the diagnosis to be performed during endoscopy. In a previous study we designed and synthesized a phosphorothioate locked nucleic acid (LNA)/ 2’ O-methyl RNA (2’OMe) probe using standard phosphoramidite chemistry and FISH hybridization was then successfully performed both on adhered and suspended bacteria at 37°C. In this work we simplified, shortened and adapted FISH to work at gastric pH values, meaning that the hybridization step now takes only 30 minutes and, in addition to the buffer, uses only urea and probe at non-toxic concentrations. Importantly, the sensitivity and specificity of the FISH method was maintained in the range of conditions tested, even at low stringency conditions (e.g., low pH). In conclusion, this methodology is a promising approach that might be used in vivo in the future in combination with a confocal laser endomicroscope for H. pylori visualization.
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Affiliation(s)
- Sílvia Fontenete
- LEPABE, Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Porto, Portugal
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
- Nucleic Acid Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense M, Denmark
- ICBAS, Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
- * E-mail:
| | - Marina Leite
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
| | - Nuno Guimarães
- LEPABE, Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Porto, Portugal
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
- Nucleic Acid Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense M, Denmark
| | - Pedro Madureira
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- ICBAS, Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
- IBMC, Institute for Molecular Biology and Cell Biology, Porto, Portugal
| | - Rui Manuel Ferreira
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
| | - Céu Figueiredo
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
- FMUP, Faculty of Medicine of Porto University, Porto, Portugal
| | - Jesper Wengel
- IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
| | - Nuno Filipe Azevedo
- LEPABE, Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Porto, Portugal
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Li B, Li YM, Guo JW, Wei YC. Relationship between Helicobacter pylori infection and gastric cancer. Shijie Huaren Xiaohua Zazhi 2015; 23:1083-1089. [DOI: 10.11569/wcjd.v23.i7.1083] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer is one of the most common malignancies worldwide, and Helicobacter pylori (H. pylori) infection is the most important risk factor. More than 50% of the world population is infected by H. pylori, but less than 2% develop gastric cancer. Other risk factors like host and environmental factors also play a role in the occurrence of gastric cancer. The pathogenesis of gastric cancer is a multi-factorial and multi-step process, and its outcome is influenced by a combination of host, bacterial, and environmental factors.
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Almeida N, Donato MM, Romãozinho JM, Luxo C, Cardoso O, Cipriano MA, Marinho C, Fernandes A, Sofia C. Correlation of Helicobacter pylori genotypes with gastric histopathology in the central region of a South-European country. Dig Dis Sci 2015; 60:74-85. [PMID: 25142169 DOI: 10.1007/s10620-014-3319-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Accepted: 08/01/2014] [Indexed: 12/30/2022]
Abstract
BACKGROUND Outcome of Helicobacter pylori (H. pylori) infection results from interaction of multiple variables including host, environmental and bacterial-associated virulence factors. AIM This study aimed to investigate the correlation of cagA, cagE, vacA, iceA and babA2 genotypes with gastric histopathology and disease phenotype in the central region of a South-European country. METHODS This prospective study involved 148 infected patients (110 female; mean age 43.5 ± 13.4 years) submitted to endoscopy with corpus and antrum biopsies. H. pylori was cultured and DNA extracted from the isolates. Genotypes were determined by PCR. Histopathological features were graded according to the updated Sydney system and OLGA/OLGIM classification. Only patients with single H. pylori genotypes and complete histopathological results were included. RESULTS Antrum samples presented higher degrees of atrophy, intestinal metaplasia, chronic inflammation and neutrophil activity. Genotype distribution was as follows: cagA-31.8 %; cagE-45.9 %; vacA s1a-24.3 %; vacA s1b-19.6 %; vacA s1c-0.7 %; vacA s2-55.4 %; vacA m1-20.9 %; vacA m2-79.1 %; vacA s1m1-18.9 %; vacA s1m2-25.7 %; vacA s2m1-2 %; vacA s2m2-53.4 %; iceA1-33.8 %; iceA2-66.2 %; babA2-12.2 %. CagA genotype was significantly associated with higher degrees of intestinal metaplasia, neutrophil activity, chronic inflammation and OLGIM stages. BabA2 was linked with higher H. pylori density. Strains with vacA s1m1 or vacA s1m1 + cagA positive genotypes had a significant association with peptic ulcer and vacA s2m2 with iron-deficient anemia. CONCLUSIONS cagA, vacA s1m1 and babA2 genotypes are relatively rare in the central region of Portugal. cagA-positive strains are correlated with more severe histopathological modifications. This gene is commonly associated with vacA s1m1, and such isolates are frequently found in patients with peptic ulcer.
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Affiliation(s)
- Nuno Almeida
- Gastroenterology Department, Coimbra University Hospital Centre, Praceta Mota Pinto e Avenida Bissaya Barreto, 3000-075, Coimbra, Portugal,
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Braga LLBC, Oliveira MAAD, Gonçalves MHRB, Chaves FK, Benigno TGDS, Gomes AD, Silva CISM, Anacleto C, Batista SDA, Queiroz DMM. CagA phosphorylation EPIYA-C motifs and the vacA i genotype in Helicobacter pylori strains of asymptomatic children from a high-risk gastric cancer area in northeastern Brazil. Mem Inst Oswaldo Cruz 2014; 109:1045-9. [PMID: 25494468 PMCID: PMC4325609 DOI: 10.1590/0074-0276140279] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2014] [Accepted: 11/11/2014] [Indexed: 12/16/2022] Open
Abstract
Helicobacter pylori infection is one of the most common infections worldwide and is associated with gastric diseases. Virulence factors such as VacA and CagA have been shown to increase the risk of these diseases. Studies have suggested a causal role of CagA EPIYA-C in gastric carcinogenesis and this factor has been shown to be geographically diverse. We investigated the number of CagA EPIYA motifs and the vacA i genotypes in H. pylori strains from asymptomatic children. We included samples from 40 infected children (18 females and 22 males), extracted DNA directly from the gastric mucus/juice (obtained using the string procedure) and analysed the DNA using polymerase chain reaction and DNA sequencing. The vacA i1 genotype was present in 30 (75%) samples, the i2 allele was present in nine (22.5%) samples and both alleles were present in one (2.5%) sample. The cagA-positive samples showed distinct patterns in the 3’ variable region of cagA and 18 of the 30 (60%) strains contained 1 EPIYA-C motif, whereas 12 (40%) strains contained two EPIYA-C motifs. We confirmed that the studied population was colonised early by the most virulent H. pylori strains, as demonstrated by the high frequency of the vacA i1 allele and the high number of EPIYA-C motifs. Therefore, asymptomatic children from an urban community in Fortaleza in northeastern Brazil are frequently colonised with the most virulent H. pylori strains.
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Affiliation(s)
- Lucia Libanez Bessa Campelo Braga
- Unidade de Pesquisa Clínica, Departamento de Medicina Interna, Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, Fortaleza, CE, Brasil
| | - Maria Aparecida Alves de Oliveira
- Unidade de Pesquisa Clínica, Departamento de Medicina Interna, Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, Fortaleza, CE, Brasil
| | - Maria Helane Rocha Batista Gonçalves
- Unidade de Pesquisa Clínica, Departamento de Medicina Interna, Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, Fortaleza, CE, Brasil
| | - Fernando Kennedy Chaves
- Unidade de Pesquisa Clínica, Departamento de Medicina Interna, Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, Fortaleza, CE, Brasil
| | - Tiago Gomes da Silva Benigno
- Unidade de Pesquisa Clínica, Departamento de Medicina Interna, Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, Fortaleza, CE, Brasil
| | - Adriana Dias Gomes
- Laboratório de Pesquisa em Bacteriologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - Cícero Igor Simões Moura Silva
- Unidade de Pesquisa Clínica, Departamento de Medicina Interna, Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, Fortaleza, CE, Brasil
| | - Charles Anacleto
- Laboratório de Pesquisa em Bacteriologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - Sérgio de Assis Batista
- Laboratório de Pesquisa em Bacteriologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
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Helicobacter pylori vacA i region polymorphism but not babA2 status associated to gastric cancer risk in northwestern Iran. Clin Exp Med 2014; 16:57-63. [PMID: 25472424 DOI: 10.1007/s10238-014-0327-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Accepted: 11/22/2014] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori-specific genotypes have been strongly associated with an increased risk of gastric cancer (GC). The aim of the present work was to study the associations of H. pylori virulence factors, vacA i region polymorphisms and babA2 status with GC risk in Azerbaijan patients. The DNA extracted from gastric biopsy specimens was used to access the babA2 and vacA genotypes. Overall, babA2 was present in 85.39 % (76/89) of H. pylori strains: 19 out of 24 (79.16 %) strains from GC, 16 out of 17 (94.14 %) strains from peptic ulcer disease (PUD) and 41 out of 48 (85.14 %) strains from chronic gastritis. No significant association was found between babA2 genotype and clinical outcomes (P > 0.05). i1 vacA polymorphism was detected in 46/89 (51.68 %) strains: in 21/24 (87.5 %), 6/17 (35.29 %) and 19/48 (39.58 %) patients with GC, PUD and chronic gastritis, respectively. i2 allele was detected in 43 (48.31 %) out of all 89 strains examined: 3 (14.28 %) of 24 strains from GC, 11 (64.71 %) of 17 from PUD, and 29 (60.42 %) of 48 strains from chronic gastritis. In this study, multiple linear regression analysis confirmed the strong association of i1 allele with GC (partial regression correlation 0.455 ± 0.101; P = 0). Results of multiple logistic regression analysis showed that vacA i1 genotype was significantly associated with GC compared with a control group (gastritis) (odds ratio 13.142, 95 % CI 3.116-55.430; P = 0). Findings from the measurement of H. pylori babA2 and vacA genotypes indicate a strong correlation between the vacA i1 allele and GC risk in the Azerbaijan area of Iran.
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Ferreira RM, Machado JC, Figueiredo C. Clinical relevance of Helicobacter pylori vacA and cagA genotypes in gastric carcinoma. Best Pract Res Clin Gastroenterol 2014; 28:1003-15. [PMID: 25439067 DOI: 10.1016/j.bpg.2014.09.004] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2014] [Revised: 08/21/2014] [Accepted: 09/15/2014] [Indexed: 02/08/2023]
Abstract
Helicobacter pylori infection is the major etiological factor of gastric carcinoma. This disease is the result of a long, multistep, and multifactorial process, which occurs only in a small proportion of patients infected with H. pylori. Gastric carcinoma development is influenced by host genetic susceptibility factors, environmental factors, and H. pylori virulence. H. pylori is genetically highly variable, and variability that affects H. pylori virulence factors may be useful to identify strains with different degrees of pathogenicity. This review will focus on VacA and CagA that have polymorphic regions that impact their functional properties. The characterization of H. pylori vacA and cagA-associated could be useful for identifying patients at highest risk of disease, who could be offered H. pylori eradication therapy and who could be included in programs of more intensive surveillance in an attempt to reduce gastric carcinoma incidence.
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Affiliation(s)
- Rui M Ferreira
- Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Portugal
| | - José C Machado
- Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Portugal; Department of Pathology and Oncology, Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Ceu Figueiredo
- Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Portugal; Department of Pathology and Oncology, Faculty of Medicine of the University of Porto, Porto, Portugal.
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Cizginer S, Ordulu Z, Kadayifci A. Approach to Helicobacter pylori infection in geriatric population. World J Gastrointest Pharmacol Ther 2014; 5:139-147. [PMID: 25133042 PMCID: PMC4133439 DOI: 10.4292/wjgpt.v5.i3.139] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Revised: 03/04/2014] [Accepted: 04/29/2014] [Indexed: 02/06/2023] Open
Abstract
The prevalence of Helicobacter pylori (H. pylori) infection and its complications increase with age. The majority of infected individuals remain asymptomatic throughout the life but 10%-20% develops peptic ulcer disease and 1% gastric malignancies. The incidence of ulcers and their complications are more common in the older population resulting in higher hospitalization and mortality rates. The increased use of medications causing gastric mucosal damage and the decreased secretion of protective prostaglandins in elderly are major factors increasing gastric mucosal sensitivity to the destructive effects of H. pylori. Due to higher prevalence of gastrointestinal (GI) malignancies, upper GI endoscopy is mostly preferred in elderly for the diagnosis of infection. Therefore, “endoscopy and treat” strategy may be more appropriate instead of “test and treat” strategy for dyspeptic patients in older age. Urea breath test and stool antigen test can be used for control of eradication, except for special cases requiring follow-up with endoscopy. The indications for treatment and suggested eradication regimens are similar with other age groups; however, the eradication failure may be a more significant problem due to high antibiotic resistance and low compliance rate in elderly. Multidrug usage and drug interactions should always be considered before starting the treatment. This paper reviews briefly the epidemiology, diagnosis, disease manifestations, and treatment options of H. pylori in the geriatric population.
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Lopes AI, Vale FF, Oleastro M. Helicobacter pylori infection - recent developments in diagnosis. World J Gastroenterol 2014; 20:9299-9313. [PMID: 25071324 PMCID: PMC4110561 DOI: 10.3748/wjg.v20.i28.9299] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
Considering the recommended indications for Helicobacter pylori (H. pylori) eradication therapy and the broad spectrum of available diagnostic methods, a reliable diagnosis is mandatory both before and after eradication therapy. Only highly accurate tests should be used in clinical practice, and the sensitivity and specificity of an adequate test should exceed 90%. The choice of tests should take into account clinical circumstances, the likelihood ratio of positive and negative tests, the cost-effectiveness of the testing strategy and the availability of the tests. This review concerns some of the most recent developments in diagnostic methods of H. pylori infection, namely the contribution of novel endoscopic evaluation methodologies for the diagnosis of H. pylori infection, such as magnifying endoscopy techniques and chromoendoscopy. In addition, the diagnostic contribution of histology and the urea breath test was explored recently in specific clinical settings and patient groups. Recent studies recommend enhancing the number of biopsy fragments for the rapid urease test. Bacterial culture from the gastric biopsy is the gold standard technique, and is recommended for antibiotic susceptibility test. Serology is used for initial screening and the stool antigen test is particularly used when the urea breath test is not available, while molecular methods have gained attention mostly for detecting antibiotic resistance.
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Bessède E, Dubus P, Mégraud F, Varon C. Helicobacter pylori infection and stem cells at the origin of gastric cancer. Oncogene 2014; 34:2547-55. [DOI: 10.1038/onc.2014.187] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2014] [Revised: 05/08/2014] [Accepted: 05/23/2014] [Indexed: 02/06/2023]
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40
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Mitchell HM, Rocha GA, Kaakoush NO, O’Rourke JL, Queiroz DMM. The Family Helicobacteraceae. THE PROKARYOTES 2014:337-392. [DOI: 10.1007/978-3-642-39044-9_275] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Calvet X, Ramírez Lázaro MJ, Lehours P, Mégraud F. Diagnosis and epidemiology of Helicobacter pylori infection. Helicobacter 2013; 18 Suppl 1:5-11. [PMID: 24011238 DOI: 10.1111/hel.12071] [Citation(s) in RCA: 93] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
A limited amount of new information was published in the field of diagnosis and epidemiology of Helicobacter pylori this last year. Besides some improvement in current tests, it is interesting to note the attempts to identify severe disease, for example gastric cancer, by breath analysis using nanomaterial-based sensors. In contrast, the predictive value for gastric cancer and atrophy of pepsinogen determinations was found inadequate. Prevalence studies of H. pylori infection have been carried out in adults and children around the world in the general population but also in specific communities. The usual risk factors were found. In addition, a Japanese study highlighted the role of grandmothers in the familial transmission of H. pylori. A study showed that the infection may not always readily establish itself in children, given the number of transient infections observed. It was also noted that after eradication, a first-year relapse is likely to be a recurrence of the previous infection, while later on it is probably a reinfection with a new strain.
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Affiliation(s)
- Xavier Calvet
- Department of Gastroenterology, Hospital de Sabadell, Barcelona, Spain; Departament de Medicina, Universitat Autonoma de Barcelona and CIBEREHD, Barcelona, Spain
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