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Mahdizade Ari M, Scholz KJ, Cieplik F, Al-Ahmad A. Viable but non-cultivable state in oral microbiota: a critical review of an underexplored microbial survival strategy. Front Cell Infect Microbiol 2025; 15:1533768. [PMID: 40171166 PMCID: PMC11959090 DOI: 10.3389/fcimb.2025.1533768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Accepted: 02/19/2025] [Indexed: 04/03/2025] Open
Abstract
The viable but non-cultivable (VBNC) state and persister cells, two dormancy phenomena in bacteria, differ in various aspects. The entry of bacteria into the VBNC state as a survival strategy under stressful conditions has gained increasing attention in recent years, largely due to the higher tolerance of VBNC cells to antibiotics and antimicrobials resulting from their low metabolic activity. The oral cavity favors biofilm growth in dental hard tissues, resulting in tooth decay and periodontitis. Despite advances in VBNC state detection in the food industry and environment, the entry capability of oral bacteria into the VBNC state remains poorly documented. Furthermore, the VBNC state has recently been observed in oral pathogens, including Porphyromonas gingivalis, which shows potential relevance in chronic systemic infections, Enterococcus faecalis, an important taxon in endodontic infections, and Helicobacter pylori, which exhibits transient presence in the oral cavity. Further research could create opportunities to develop novel therapeutic strategies to control oral pathogens. The inability of conventional culture-based methods to identify VBNC bacteria and the metabolic reactivation of dormant cells to restore susceptibility to therapies highlights a notable gap in anti-VBNC state strategies. The lack of targeted approaches tested for efficacy against VBNC bacteria underscores the need to develop novel detection methods. This review discusses the VBNC state, its importance in public health, and diagnostic techniques, with a special focus on the VBNC state in oral bacteria.
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Affiliation(s)
- Marzie Mahdizade Ari
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Konstantin Johannes Scholz
- Department of Operative Dentistry and Periodontology, Center for Dental Medicine, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany
| | - Fabian Cieplik
- Department of Operative Dentistry and Periodontology, Center for Dental Medicine, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany
| | - Ali Al-Ahmad
- Department of Operative Dentistry and Periodontology, Center for Dental Medicine, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany
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Bhattacharjee A, Sahoo OS, Sarkar A, Bhattacharya S, Chowdhury R, Kar S, Mukherjee O. Infiltration to infection: key virulence players of Helicobacter pylori pathogenicity. Infection 2024; 52:345-384. [PMID: 38270780 DOI: 10.1007/s15010-023-02159-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 12/13/2023] [Indexed: 01/26/2024]
Abstract
PURPOSE This study aims to comprehensively review the multifaceted factors underlying the successful colonization and infection process of Helicobacter pylori (H. pylori), a prominent Gram-negative pathogen in humans. The focus is on elucidating the functions, mechanisms, genetic regulation, and potential cross-interactions of these elements. METHODS Employing a literature review approach, this study examines the intricate interactions between H. pylori and its host. It delves into virulence factors like VacA, CagA, DupA, Urease, along with phase variable genes, such as babA, babC, hopZ, etc., giving insights about the bacterial perspective of the infection The association of these factors with the infection has also been added in the form of statistical data via Funnel and Forest plots, citing the potential of the virulence and also adding an aspect of geographical biasness to the virulence factors. The biochemical characteristics and clinical relevance of these factors and their effects on host cells are individually examined, both comprehensively and statistically. RESULTS H. pylori is a Gram-negative, spiral bacterium that successfully colonises the stomach of more than half of the world's population, causing peptic ulcers, gastric cancer, MALT lymphoma, and other gastro-duodenal disorders. The clinical outcomes of H. pylori infection are influenced by a complex interplay between virulence factors and phase variable genes produced by the infecting strain and the host genetic background. A meta-analysis of the prevalence of all the major virulence factors has also been appended. CONCLUSION This study illuminates the diverse elements contributing to H. pylori's colonization and infection. The interplay between virulence factors, phase variable genes, and host genetics determines the outcome of the infection. Despite biochemical insights into many factors, their comprehensive regulation remains an understudied area. By offering a panoramic view of these factors and their functions, this study enhances understanding of the bacterium's perspective, i.e. H. pylori's journey from infiltration to successful establishment within the host's stomach.
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Affiliation(s)
- Arghyadeep Bhattacharjee
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India
- Department of Microbiology, Kingston College of Science, Beruanpukuria, Barasat, West Bengal, 700219, India
| | - Om Saswat Sahoo
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India
| | - Ahana Sarkar
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India
| | - Saurabh Bhattacharya
- Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, The Hebrew University of Jerusalem, P.O.B. 12272, 9112001, Jerusalem, Israel
| | - Rukhsana Chowdhury
- School of Biological Sciences, RKM Vivekananda Educational and Research Institute Narendrapur, Kolkata, India
| | - Samarjit Kar
- Department of Mathematics, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India
| | - Oindrilla Mukherjee
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India.
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Qin C, Huang GR, Guan AX, Zhou WT, Chen H, Luo PP, Luo XK, Huang YQ, Huang ZS. Mechanistic research: Selenium regulates virulence factors, reducing adhesion ability and inflammatory damage of Helicobacter pylori. World J Gastroenterol 2024; 30:91-107. [PMID: 38293320 PMCID: PMC10823904 DOI: 10.3748/wjg.v30.i1.91] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 11/22/2023] [Accepted: 12/13/2023] [Indexed: 01/06/2024] Open
Abstract
BACKGROUND The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host. Although selenium is closely related to pathogenicity as an environmental factor, the specific correlation between them remains unclear. AIM To investigate how selenium acts on virulence factors and reduces their toxicity. METHODS H. pylori strains were induced by sodium selenite. The expression of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin gene A (VacA) was determined by quantitative PCR and Western blotting. Transcriptomics was used to analyze CagA, CagM, CagE, Cag1, Cag3, and CagT. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction, and H. pylori colonization, inflammatory reactions, and the cell adhesion ability of H. pylori were assessed. RESULTS CagA and VacA expression was upregulated at first and then downregulated in the H. pylori strains after sodium selenite treatment. Their expression was significantly and steadily downregulated after the 5th cycle (10 d). Transcriptome analysis revealed that sodium selenite altered the levels affect H. pylori virulence factors such as CagA, CagM, CagE, Cag1, Cag3, and CagT. Of these factors, CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite. Moreover, CagT expression was upregulated before the 3rd cycle (6 d) and significantly downregulated after the 5th cycle. Cag1 and Cag3 expression was upregulated and downregulated, respectively, but no significant change was observed by the 5th cycle. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction. The extent of H. pylori colonization in the stomach increased; however, sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H. pylori-infected mice, and the cell adhesion ability of H. pylori was significantly weakened. CONCLUSION These results demonstrate that H. pylori displayed virulence attenuation after the 10th d of sodium selenite treatment. Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H. pylori, thus mitigating the inflammatory damage to the gastric mucosa.
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Affiliation(s)
- Chun Qin
- Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
- Department of Digestive Diseases, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Gan-Rong Huang
- Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Ai-Xing Guan
- Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
- Department of Digestive Diseases, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Wen-Ting Zhou
- Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Hao Chen
- Department of Pathology, Wannan Medical College, Wuhu 241002, Anhui Province, China
| | - Pei-Pei Luo
- Department of Gastroenterology, Wujin People’s Hospital affiliated to Jiangsu University, Changzhou 213004, Jiangsu Province, China
| | - Xian-Ke Luo
- Department of Gastroenterology, Guangzhou Liwan District People's Hospital, Guangzhou 510370, Guangdong Province, China
| | - Yan-Qiang Huang
- Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Zan-Song Huang
- Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
- Department of Digestive Diseases, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
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Rezaei F, Alebouyeh M, Mirbagheri SZ, Ebrahimi A, Foroushani AR, Bakhtiari R. Transcriptional analysis of Helicobacter pylori cytotoxic-associated gene-pathogenicity island in response to different pH levels and proton pump inhibitor exposure. Indian J Gastroenterol 2023; 42:686-693. [PMID: 37665542 DOI: 10.1007/s12664-023-01422-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 06/21/2023] [Indexed: 09/05/2023]
Abstract
BACKGROUND Long-term use of proton pump inhibitors (PPIs) can increase the risk of gastric cancer in Helicobacter pylori-infected patients; nevertheless, there is no data about their impact on the pathogenicity of H. pylori. This study aimed at investigating the transcriptional alteration of key gene mediators of cytotoxin-associated gene-pathogenicity island (cag-PAI) among clinical H. pylori isolates in response to omeprazole at different pH levels. METHODS Accordingly, H. pylori isolates with the same virulence genotypes selected from the gastric biopsies of patients and transcriptional alteration in the cag-PAI genes studied in the presence or absence of omeprazole (2 mg/mL) at pH 2.0, 4.0 and 7.0 after 30 and 90 minutes of the treatment. Relative changes in the transcriptional levels were recorded in each assay, separately. RESULTS Of 18 H. pylori isolates, the cag-PAI empty site was detected in four strains, while the presence of cagA, cagL and cagY was characterized in 77.7%, 83.3% and 83.3% of the cag-PAI-positive strains, respectively. Transcriptional analysis of the selected strains showed up-regulation of cagA and cagL, mainly at pH 2.0 and 4.0 after 30 and 90-minute exposure. A diversity in the expression levels of cag-PAI genes was seen among the strains at the extent and time of induction. CONCLUSION Our results showed that omeprazole could increase the expression of H. pylori cagA and cagL at acidic pH. Heterogeneity among the strains probably has an impact on the extent of their interplay with PPIs. Further studies are needed to establish this correlation.
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Affiliation(s)
- Fatemeh Rezaei
- Department of Pathobiology, School of Public Health and Institute Health Research, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Alebouyeh
- Pediatric Infections Research Centre, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyedeh Zohre Mirbagheri
- Department of Pathobiology, School of Public Health and Institute Health Research, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Ebrahimi
- Department of Pathobiology, School of Public Health and Institute Health Research, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas Rahimi Foroushani
- Department of Epidemiology and Biostatistics, School of Public Health and Institute Health Research, Tehran University of Medical Sciences, Tehran, Iran
| | - Ronak Bakhtiari
- Department of Pathobiology, School of Public Health and Institute Health Research, Tehran University of Medical Sciences, Tehran, Iran.
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Ahmadzadeh A, Rashidi M, Mohsenifar Z, Faeghi F, Rezaei-Tavirani M, Ahmadi N, Zali MR, Alebouyeh M, Feizi M, Ahmadzadeh Z. Examining the effect of Helicobacter pylori cagPAI variety on gene expression pattern related to gastric cancer. Horm Mol Biol Clin Investig 2023; 44:251-258. [PMID: 36872607 DOI: 10.1515/hmbci-2022-0048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 02/08/2023] [Indexed: 03/07/2023]
Abstract
OBJECTIVES We aimed to determine possible association between heterogeneity of Helicobacter pylori cytotoxin-associated gene pathogenicity island and gene expression profiles in patients with distinct histopathological changes. METHODS Gastric biopsies were obtained from seventy five patients. Microbiological and pathological examinations were done and intactness of Helicobacter pylori cagPAI was determined by PCR using 11 pairs of primers flanking cagζ-cagA regions and cagPAI empty site. Alterations at mRNA levels of eight genes were investigated by real-time PCR and their association with cagPAI intactness and histopathological changes examined statistically. RESULTS A larger proportion of cagPAI positive strains colonized patients with SAG (52.4%), followed by CG (33.3%), and IM (14.3%). Intact cagPAI was found in 87.5% of the strains obtained from patients with SAG, while significantly lower frequency was detected among those with CG (12.5%) and IM (0%). No significant difference was found among the studied histological groups and fold changes in gene expression of gastric biopsies of Helicobacter pylori infected patients with distinct cagPAI status. However, in each histological group, the strains with more complete gene cluster induced (ErbB2, CCNE1, CTNNB1, and MMP7 in SAG and IM groups) or reduced (TP53, in CG group) expression of the GC associated genes in relatively higher levels. APC, TP53 and E-cadherin were down-regulated in patients with SAG and IM compared with CG patients, irrespective to the status of cagPAI integrity. CONCLUSIONS Helicobacter pylori strains that carry more complete cagPAI segment could induce remarkably higher levels of mRNA changes of GC associated genes in all histopathological groups.
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Affiliation(s)
- Alireza Ahmadzadeh
- School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohsen Rashidi
- Department of Physiology and Pharmacology, School of Medicine, Mazandaran University of Medical Sciences, Mazandaran, Iran
| | - Zhaleh Mohsenifar
- Department of Pathology, School of Medicine, Ayatollah Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fariborz Faeghi
- Department of Radiation Technology, Paramedical Sciences Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mostafa Rezaei-Tavirani
- School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nayebali Ahmadi
- School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masoud Alebouyeh
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Pediatric Infections Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Feizi
- Faculty of Medical Sciences, Hamedan University of Medical Sciences, Hamedan, Iran
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Yang F, Zhang J, Wang S, Sun Z, Zhou J, Li F, Liu Y, Ding L, Liu Y, Chi W, Liu T, He Y, Xiang P, Bao Z, Olszewski MA, Zhao H, Zhang Y. Genomic population structure of Helicobacter pylori Shanghai isolates and identification of genomic features uniquely linked with pathogenicity. Virulence 2021; 12:1258-1270. [PMID: 33904371 PMCID: PMC8081043 DOI: 10.1080/21505594.2021.1920762] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 04/01/2021] [Accepted: 04/19/2021] [Indexed: 02/08/2023] Open
Abstract
Severe Helicobacter pylori-linked gastric disorders are especially prevalent in the East Asia region. The ability of H. pylori to cause different clinical outcomes is thought to be associated with unique sets of its genetic features. However, only few genetic features have been definitively linked to specific gastrointestinal pathologies. Genome heterogeneity of clinical H. pylori strains from patients with four different gastric disorders was studied to explore the population structure and molecular genomic features and their association with pathogenicity. Population analysis showed that 92.9% of the Shanghai H. pylori isolates were clustered in the East Asia group. Among 2,866 genes detected in all genomes, 1,146 genes formed the core genome, whereas 209 unique genes were detected in individual disease groups. The unique genes of peptic ulcer and gastric cancer groups represented the inorganic ion transport and metabolism function gene clusters. Sixteen virulence genes were detected with statistically different detection rates among the four disease groups. Furthermore, 127 clustered regularly interspaced short palindromic repeats were found with significantly different rates in the four disease groups. A total of 337 putative genomic islands were identified, and three genomic islands were individually found in more than 10% of strains. The genomic islands included several metabolism-associated genes and many genes with unknown function. In total, 88 sequence types were detected among the 112 Shanghai H. pylori isolates. Our study provides an essential milestone in the mapping of specific genomic features and their functions to identify factors needed to induce specific gastric disorders in H. pylori.
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Affiliation(s)
- Feng Yang
- Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai, China
- Department of Laboratory Medicine, Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, China
- Department of Laboratory Medicine, Huadong Hospital, Fudan University, Shanghai, China
| | - Jinghao Zhang
- Department of Laboratory Medicine, Huadong Hospital, Fudan University, Shanghai, China
| | - Su Wang
- Department of Laboratory Medicine, Huadong Hospital, Fudan University, Shanghai, China
| | - Zhaoyang Sun
- Department of Laboratory Medicine, Huadong Hospital, Fudan University, Shanghai, China
| | - Jun Zhou
- Department of Endoscopy, Huadong Hospital, Fudan University, Shanghai, China
| | - Feng Li
- Department of Endoscopy, Huadong Hospital, Fudan University, Shanghai, China
| | - Yue Liu
- Department of Laboratory Medicine, Huadong Hospital, Fudan University, Shanghai, China
| | - Li Ding
- Department of Laboratory Medicine, Huadong Hospital, Fudan University, Shanghai, China
| | - Yixin Liu
- Department of Laboratory Medicine, Huadong Hospital, Fudan University, Shanghai, China
| | - Wenjing Chi
- Department of Laboratory Medicine, Huadong Hospital, Fudan University, Shanghai, China
| | - Tao Liu
- Department of Laboratory Medicine, Huadong Hospital, Fudan University, Shanghai, China
| | - Yongqun He
- Unit for Laboratory Animal Medicine, Department of Microbiology and Immunology, And Center for Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, USA
| | - Ping Xiang
- Department of Endoscopy, Huadong Hospital, Fudan University, Shanghai, China
| | - Zhijun Bao
- Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai, China
- Department of Laboratory Medicine, Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, China
- Department of Gastroenterology, Gerontology Institute of Shanghai, Huadong Hospital, Fudan University, Shanghai, China
| | - Michal A. Olszewski
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan and Research Service, VA Ann Arbor Healthcare System, Ann Arbor, USA
| | - Hu Zhao
- Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai, China
- Department of Laboratory Medicine, Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, China
- Department of Laboratory Medicine, Huadong Hospital, Fudan University, Shanghai, China
| | - Yanmei Zhang
- Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai, China
- Department of Laboratory Medicine, Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, China
- Department of Laboratory Medicine, Huadong Hospital, Fudan University, Shanghai, China
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Yarmohammadi M, Yadegar A, Ebrahimi MT, Zali MR. Effects of a Potential Probiotic Strain Lactobacillus gasseri ATCC 33323 on Helicobacter pylori-Induced Inflammatory Response and Gene Expression in Coinfected Gastric Epithelial Cells. Probiotics Antimicrob Proteins 2021; 13:751-764. [PMID: 33206342 DOI: 10.1007/s12602-020-09721-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/20/2020] [Indexed: 12/20/2022]
Abstract
In the present study, we aimed to investigate the modulatory effects of a potential probiotic bacterium Lactobacillus gasseri ATCC 33323 on Helicobacter pylori-induced inflammatory response and gene expression in human gastric adenocarcinoma (AGS) cell line. The gastric epithelial cells were coinfected with a collection of H. pylori clinical strains alone or in combination with L. gasseri at a multiplicity of infection (MOI) of 1:100 for each bacterium, and incubated for different time points of 3, 6, and 12 h. IL-8 secretion from coinfected AGS cells after incubation at each time point was measured by an enzyme-linked immunosorbent assay (ELISA). The mRNA expression of IL-8, Bcl-2, β-catenin, integrin α5, and integrin β1 genes was determined by quantitative RT-PCR amplification of total RNA extracted from coinfected epithelial cells. L. gasseri significantly (P < 0.05 and P < 0.01) decreased the production of IL-8 in AGS cells coinfected with H. pylori strains at 6 h post-infection. We also detected that L. gasseri significantly (P < 0.05) down-regulated the gene expression level of IL-8 in H. pylori-stimulated AGS cells after 6 and 12 h of coinfection. Similarly, L. gasseri caused a significant decrease (P < 0.05) in mRNA expression of Bcl-2, β-catenin, integrin α5, and integrin β1 genes in AGS cells at 3 and 6 h after infection with H. pylori strains as compared with non-infected control cells. In conclusion, our results demonstrated that L. gasseri ameliorates H. pylori-induced inflammation and could be developed as a supplementation to the current treatment regimens administrated against H. pylori infection.
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Affiliation(s)
- Mahdieh Yarmohammadi
- Department of Biology, Faculty of Sciences, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Maryam Tajabadi Ebrahimi
- Department of Biology, Faculty of Sciences, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Alihosseini S, Ghotaslou R, Heravi FS, Ahmadian Z, Leylabadlo HE. Management of antibiotic-resistant Helicobacter pylori infection: current perspective in Iran. J Chemother 2020; 32:273-285. [PMID: 32657237 DOI: 10.1080/1120009x.2020.1790889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Helicobacter pylori is a common gastric bacterial pathogen implicated in the pathogenesis of many digestive tract disorders. H. pylori infection prevalence has been reported alarmingly in Iran. A plethora of studies have been conducted to evaluate the efficiency of first-line and second-line eradication attempts in patients diagnosed with H. pylori infections in Iran. The present study, was evaluated the efficacy of first-line and second-line therapy in H. pylori infections in Iran. We aimed to consider the literature review of the various library and electronic databases (Science Direct, PubMed, and Google Scholar) until 2020. The frequency of bacterial resistance to tetracycline, ampicillin, trimethoprim, erythromycin, ofloxacin, and metronidazolewas found to be high in Iran, while the most effective antibiotics were clarithromycin, rifampin, rifampicin, tetracycline, amoxicillin, ciprofloxacin, levofloxacin, moxifloxacin, and azithromycin. The therapeutic choice for H. pylori eradication in Iran could be quadruple therapy using two antibiotics amoxicillin and metronidazole/clarithromycin for the first-line regimen, and a combination of furazolidone plus tetracycline/amoxicillin and bismuth plus proton pump inhibitor for the second-line regimen. Due to increased antibiotic resistance in our region, empirical therapy must be replaced by more targeted treatment based on antimicrobial drug resistance profiles obtained from patients. Although we limited our investigation on the H. pylori eradication regimens in Iran, the results can be generalized to any region as long as the patterns of resistance are the same.
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Affiliation(s)
- Samin Alihosseini
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Ghotaslou
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Bacteriology and Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Zainab Ahmadian
- Department of Pharmaceutics, School of Pharmacy, Zanjan University of Medical Science, Zanjan, Iran
| | - Hamed Ebrahimzadeh Leylabadlo
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Bacteriology and Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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9
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Genetic variation in the cag pathogenicity island of Helicobacter pylori strains detected from gastroduodenal patients in Thailand. Braz J Microbiol 2020; 51:1093-1101. [PMID: 32410092 DOI: 10.1007/s42770-020-00292-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Accepted: 04/30/2020] [Indexed: 12/26/2022] Open
Abstract
There is a lack of evidence of genetic variation in the Helicobacter pylori cag-PAI in Thailand, a region with the low incidence of gastric cancer. To clarify this issue, variation in the H. pylori cag-PAI in strains detected in Thailand was characterized and simultaneously compared with strains isolated from a high-risk population in Korea. The presence of ten gene clusters within cag-PAI (cagA, cagE, cagG, cagH, cagL, cagM, cagT, orf13, virB11, and orf10) and IS605 was characterized in H. pylori strains detected from these two countries. The cagA genotypes and EPIYA motifs were analyzed by DNA sequencing. The overall proportion of the ten cag-PAI genes that were detected ranged between 66 and 79%; additionally, approximately 48% of the strains from Thai patients contained an intact cag-PAI structure, while a significantly higher proportion (80%) of the strains from Korean patients had an intact cag-PAI. A significantly higher proportion of IS605 was detected in strains from Thai patients (55%). Analysis of cagA genotypes and EPIYA motifs revealed a higher frequency of Western-type cagA in Thai patients (87%) relative to Korean patients (8%) who were predominately associated with the East Asian-type cagA (92%). Variations in the Western-type cagA in the Thai population, such as EPIYA-BC patterns and EPIYA-like sequences (EPIYT), were mainly detected as compared with the Korean population (p < 0.05). In summary, H. pylori strains that colonize the Thai population tend to be associated with low virulence due to distinctive cag-PAI variation, which may partially explain the Asian paradox phenomenon in Thailand.
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Sukri A, Hanafiah A, Mohamad Zin N, Kosai NR. Epidemiology and role of Helicobacter pylori virulence factors in gastric cancer carcinogenesis. APMIS 2020; 128:150-161. [PMID: 32352605 DOI: 10.1111/apm.13034] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 02/09/2020] [Indexed: 02/06/2023]
Abstract
Infection with Helicobacter pylori is associated with the development of gastric cancer. Although the prevalence of gastric cancer has declined throughout years due to improvement in early screening strategy, mortality due to gastric cancer has not changed. Incidence and mortality due to gastric cancer are higher in developing countries as compared to developed countries. Diagnosis and prognosis of gastric cancer are still poor with patients usually diagnosed with cancer at an advanced stage. Eradication of H. pylori is pertinent for the prevention of gastric cancer. However, the rise in antimicrobial resistance among H. pylori isolates has complicated the prevention strategy. H. pylori express multiple virulence factors for survival in the hostile acid gastric environment. The expression of oncogenic protein cytotoxin-associated gene A (CagA), vacuolating cytotoxin A (VacA), and outer inflammatory protein is essential for H. pylori to exert pathogenesis towards the host. Interestingly, <3% of H. pylori-infected subjects develop gastric cancer, suggesting a unique way of interaction between the host's immune response and H. pylori virulence factors. This article is aimed to review the epidemiology and role of H. pylori in gastric carcinogenesis. A better understanding of the interaction between H. pylori virulence factors and host is required for better gastric cancer prevention.
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Affiliation(s)
- Asif Sukri
- Programme of Biomedical Science, Faculty of Health Science, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Alfizah Hanafiah
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Noraziah Mohamad Zin
- Programme of Biomedical Science, Faculty of Health Science, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Nik Ritza Kosai
- Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
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Ansari S, Yamaoka Y. Helicobacter pylori Virulence Factors Exploiting Gastric Colonization and its Pathogenicity. Toxins (Basel) 2019; 11:677. [PMID: 31752394 PMCID: PMC6891454 DOI: 10.3390/toxins11110677] [Citation(s) in RCA: 156] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 11/15/2019] [Accepted: 11/16/2019] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori colonizes the gastric epithelial cells of at least half of the world's population, and it is the strongest risk factor for developing gastric complications like chronic gastritis, ulcer diseases, and gastric cancer. To successfully colonize and establish a persistent infection, the bacteria must overcome harsh gastric conditions. H. pylori has a well-developed mechanism by which it can survive in a very acidic niche. Despite bacterial factors, gastric environmental factors and host genetic constituents together play a co-operative role for gastric pathogenicity. The virulence factors include bacterial colonization factors BabA, SabA, OipA, and HopQ, and the virulence factors necessary for gastric pathogenicity include the effector proteins like CagA, VacA, HtrA, and the outer membrane vesicles. Bacterial factors are considered more important. Here, we summarize the recent information to better understand several bacterial virulence factors and their role in the pathogenic mechanism.
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Affiliation(s)
- Shamshul Ansari
- Department of Microbiology, Chitwan Medical College and Teaching Hospital, Bharatpur 44200, Chitwan, Nepal;
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan
- Global Oita Medical Advanced Research Center for Health, Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, 2002 Holcombe Blvd., Houston, TX 77030, USA
- Borneo Medical and Health Research Centre, Universiti Malaysia Sabah, Kota Kinabaru, Sabah 88400, Malaysia
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Farzi N, Yadegar A, Sadeghi A, Asadzadeh Aghdaei H, Marian Smith S, Raymond J, Suzuki H, Zali MR. High Prevalence of Antibiotic Resistance in Iranian Helicobacter pylori Isolates: Importance of Functional and Mutational Analysis of Resistance Genes and Virulence Genotyping. J Clin Med 2019; 8:2004. [PMID: 31744181 PMCID: PMC6912791 DOI: 10.3390/jcm8112004] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 11/11/2019] [Accepted: 11/14/2019] [Indexed: 12/14/2022] Open
Abstract
The high prevalence of antibiotic resistance in Helicobacter pylori has become a great challenge in Iran. The genetic mutations that contribute to the resistance have yet to be precisely identified. This study aimed to investigate the prevalence of antibiotic resistance and virulence markers in Iranian H. pylori isolates and to analyze if there is any association between resistance and genotype. Antibiotic susceptibility patterns of 68 H. pylori isolates were investigated against metronidazole, clarithromycin, amoxicillin, rifampicin, ciprofloxacin, levofloxacin, and tetracycline by the agar dilution method. The frxA, rdxA, gyrA, gyrB, and 23S rRNA genes of the isolates were sequenced. The virulence genotypes were also determined using PCR. Metronidazole resistance was present in 82.4% of the isolates, followed by clarithromycin (33.8%), ciprofloxacin (33.8%), rifampicin (32.4%), amoxicillin (30.9%), levofloxacin (27.9%), and tetracycline (4.4%). Overall, 75% of the isolates were resistant to at least two antibiotics tested and considered as a multidrug resistance (MDR) phenotype. Most of the metronidazole-resistant isolates carried frameshift mutations in both frxA and rdxA genes, and premature termination occurred in positions Q5Stop and Q50Stop, respectively. Amino acid substitutions M191I, G208E, and V199A were predominantly found in gyrA gene of fluoroquinolone-resistant isolates. A2143G and C2195T mutations of 23S rRNA were found in four clarithromycin-resistant isolates. Interestingly, significant associations were found between resistance to metronidazole (MNZ) and cagA-, sabA-, and dupA-positive genotypes, with p = 0.0002, p = 0.0001, and p = 0.0001, respectively. Furthermore, a significant association was found between oipA "on" status and resistance to amoxicillin (AMX) (p = 0.02). The prevalence of H. pylori antibiotic resistance is high in our region, particularly that of metronidazole, clarithromycin, ciprofloxacin, and MDR. Simultaneous screening of virulence and resistance genotypes can help clinicians to choose the appropriate therapeutic regime against H. pylori infection.
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Affiliation(s)
- Nastaran Farzi
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran;
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran;
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran; (A.S.); (M.R.Z.)
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran;
| | - Sinéad Marian Smith
- School of Medicine & School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland;
| | - Josette Raymond
- Bacteriology, University of Paris-Descartes, Cochin Hospital, 75006 Paris, France;
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan;
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran; (A.S.); (M.R.Z.)
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Yadegar A, Mohabati Mobarez A, Zali MR. Genetic diversity and amino acid sequence polymorphism in Helicobacter pylori CagL hypervariable motif and its association with virulence markers and gastroduodenal diseases. Cancer Med 2019; 8:1619-1632. [PMID: 30873747 PMCID: PMC6488209 DOI: 10.1002/cam4.1941] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Revised: 11/22/2018] [Accepted: 12/03/2018] [Indexed: 12/19/2022] Open
Abstract
Genetic variability in cagL gene especially within the Helicobacter pylori CagL hypervariable motif (CagLHM) may affect the development of gastric cancer. Therefore, this study was conducted to investigate the association of CagL diversity with clinical outcomes and with H pylori virulence markers. A total of 126 patients with different gastric diseases including non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), gastric erosion (GE), and gastric cancer (GC) were enrolled. H pylori was cultured from gastric biopsies, and the isolates were screened for the presence of cagL, cagA, vacA, babA2, sabA, and cagPAI integrity by PCR. The amino acid polymorphisms of cagL were analyzed using DNA sequencing. We isolated 61 (48.4%) H pylori strains from 36 NUD, eight PUD, 12 GE, and five GC patients. Almost all isolates were cagL positive (97%), and their RGD, RHS, and SKIIVK motifs were highly conserved. Among 10 CagLHM variants identified, NEIGQ and NKIGQ were detected as the most prevalent sequences. Interestingly, a significant association was found between the presence of NKMGK and PUD (P = 0.002). Notably, the NEIGQ isolates with multiple C-type EPIYA repeat that carried intact cagPAI correlated with disease risk for PUD, GE, and GC (P = 0.021). In conclusion, we identified novel variants of H pylori CagLHM sequences in Iranian population such as NKMGK, which was associated with disease risk for PUD. Further studies using a large number of strains are required to better clarify the function of certain CagLHM motifs in gastric carcinogenesis and disease outcome.
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Affiliation(s)
- Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
| | | | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
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García-Gil A, Lopez-Bailon LU, Ortiz-Navarrete V. Beyond the antibody: B cells as a target for bacterial infection. J Leukoc Biol 2019; 105:905-913. [PMID: 30657607 DOI: 10.1002/jlb.mr0618-225r] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Revised: 12/15/2018] [Accepted: 12/26/2018] [Indexed: 12/16/2022] Open
Abstract
It is well established that B cells play an important role during infections beyond antibody production. B cells produce cytokines and are APCs for T cells. Recently, it has become clear that several pathogenic bacterial genera, such as Salmonella, Brucella, Mycobacterium, Listeria, Francisella, Moraxella, and Helicobacter, have evolved mechanisms such as micropinocytosis induction, inflammasome down-regulation, inhibitory molecule expression, apoptosis induction, and anti-inflammatory cytokine secretion to manipulate B cell functions influencing immune responses. In this review, we summarize our current understanding of B cells as targets of bacterial infection and the mechanisms by which B cells become a niche for bacterial survival and replication away from extracellular immune responses such as complement and antibodies.
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Affiliation(s)
- Abraham García-Gil
- Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico
| | - Luis Uriel Lopez-Bailon
- Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico
| | - Vianney Ortiz-Navarrete
- Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico
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Waskito LA, Yih-Wu J, Yamaoka Y. The role of integrating conjugative elements in Helicobacter pylori: a review. J Biomed Sci 2018; 25:86. [PMID: 30497458 PMCID: PMC6264033 DOI: 10.1186/s12929-018-0489-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Accepted: 11/16/2018] [Indexed: 12/15/2022] Open
Abstract
The genome of Helicobacter pylori contains many putative genes, including a genetic region known as the Integrating Conjugative Elements of H. pylori type four secretion system (ICEHptfs). This genetic regions were originally termed as "plasticity zones/regions" due to the great genetic diversity between the original two H. pylori whole genome sequences. Upon analysis of additional genome sequences, the regions were reported to be extremely common within the genome of H. pylori. Moreover, these regions were also considered conserved rather than genetically plastic and were believed to act as mobile genetic elements transferred via conjugation. Although ICEHptfs(s) are highly conserved, these regions display great allele diversity, especially on ICEHptfs4, with three different subtypes: ICEHptfs4a, 4b, and 4c. ICEHptfs were also reported to contain a novel type 4 secretion system (T4SS) with both epidemiological and in vitro infection model studies highlighting that this novel T4SS functions primarily as a virulence factor. However, there is currently no information regarding the structure, the genes responsible for forming the T4SS, and the interaction between this T4SS and other virulence genes. Unlike the cag pathogenicity island (PAI), which contains CagA, a gene found to be essential for H. pylori virulence, these novel T4SSs have not yet been reported to contain genes that contribute significant effects to the entire system. This notion prompted the hypothesis that these novel T4SSs may have different mechanisms involving cag PAI.
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Affiliation(s)
- Langgeng Agung Waskito
- Department of Environmental and Preventive Medicine, Oita University, Faculty of Medicine, Yufu City, Oita, Japan.,Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
| | - Jeng Yih-Wu
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University, Faculty of Medicine, Yufu City, Oita, Japan. .,Department of Medicine, Gastroenterology Section, Baylor College of Medicine, Houston, TX, USA. .,Global Oita Medical Advanced Research Center for Health, Yufu City, Oita, Japan.
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Markovska R, Boyanova L, Yordanov D, Stankova P, Gergova G, Mitov I. Status of Helicobacter pylori cag pathogenicity island (cagPAI) integrity and significance of its individual genes. INFECTION GENETICS AND EVOLUTION 2018; 59:167-171. [PMID: 29427761 DOI: 10.1016/j.meegid.2018.02.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Revised: 01/06/2018] [Accepted: 02/06/2018] [Indexed: 01/24/2023]
Abstract
One of the most important virulence factors of H. pylori is the intact cagPAI. The aim of the present study is to investigate cagPAI intactness among Bulgarian H. pylori isolates, its associations with clinical outcomes and vacA alleles, and to evaluate the significance of individual cagPAI genes. MATERIAL AND METHODS Totally, 156 isolates from 156 patients with endoscopic findings for duodenal or gastric ulcer (33 subjects), non-ulcer disease (121) and other diseases, such as Crohn's disease and hepatitis (2) were tested. Polymerase chain reaction (PCR) was used to detect 14 essential cagPAI genes, including cagA, as well as vacA s, i and m alleles. RESULTS CagA positive were 81.4% of all H. pylori isolates. Intact cagPAI was found in 64.1% of the all isolates, 16.7% and 19.2% showed complete and partial cagPAI absence, respectively. The prevalence of all cagPAI genes and intact cagPAI was significantly higher in isolates from ulcer patients compared with those from non-ulcer patients (p = 0.001). The most frequently missing genes among the isolates with partially deleted cagPAIs were cagE or/and cagY (28 of 30 isolates). Overall prevalence of vacA s1a allele was 80.1% and that of vacA i1 was 64.1%. The vacA s1a, m1 and i1 alleles were more prevalent in H. pylori isolates from ulcer patients (p = 0.03, p = 0.009, and p = 0.0003, respectively) and were associated with isolates with intact cagPAI. CONCLUSIONS In Bulgaria the prevalence of intact cagPAI was high. cagE or/and cagY absence was the most important predictor of cagPAI status.
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Affiliation(s)
- Rumyana Markovska
- Department of Medical Microbiology, Medical University of Sofia, 1431 Sofia, Bulgaria.
| | - Lyudmila Boyanova
- Department of Medical Microbiology, Medical University of Sofia, 1431 Sofia, Bulgaria
| | - Daniel Yordanov
- Department of Medical Microbiology, Medical University of Sofia, 1431 Sofia, Bulgaria
| | - Petya Stankova
- Department of Medical Microbiology, Medical University of Sofia, 1431 Sofia, Bulgaria
| | - Galina Gergova
- Department of Medical Microbiology, Medical University of Sofia, 1431 Sofia, Bulgaria
| | - Ivan Mitov
- Department of Medical Microbiology, Medical University of Sofia, 1431 Sofia, Bulgaria
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Functional Cytotoxin Associated Gene A in Helicobacter pylori Strains and Its Association with Integrity of Cag-pathogenicity Island and Histopathological Changes of Gastric Tissue. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2017. [DOI: 10.5812/archcid.62955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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