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Saxena P, Samanta D, Thakur P, Goh KM, Subramaniam M, Peyton BM, Fields M, Sani RK. pH-dependent genotypic and phenotypic variability in Oleidesulfovibrio alaskensis G20. Appl Environ Microbiol 2025; 91:e0256524. [PMID: 40135858 DOI: 10.1128/aem.02565-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Accepted: 02/21/2025] [Indexed: 03/27/2025] Open
Abstract
Sulfate-reducing bacteria (SRB) exhibit versatile metabolic adaptability with significant flexibility influenced by pH fluctuations, which play a critical role in biogeochemical cycles. In this study, we used a model SRB, Oleidesulfovibrio alaskensis G20, to determine the temporal effects of pH variations (pH 6, 7, and 8) on both growth dynamics and metabolic gene expressions. The specific growth rate at pH 6 (0.014 h-1) closely matched that at pH 7 (0.016 h-1), while pH 8 exhibited a lower growth rate (0.010 h-1). Lactate consumption peaked at pH 7 (0.35 mM lactate.h-1) and declined at pH 8 (0.09 mM lactate.h-1). Significant hydrogen production was evident under both acidic and alkaline conditions. Gene expression studies revealed that ATPases function as proton pumps, while hydrogenases mediate reversible proton-to-hydrogen conversion. Sulfate and energy metabolism act as electron acceptors and donors, while amino acid synthesis regulates basic and acidic amino acids to mitigate pH stress. Downregulation of FtsZ at pH 6 suggests impaired division, correlating with slightly longer lengths (~2 µm), while upregulation of divisome proteins at pH 8 suggests efficient division processes, aligning with shorter lengths (~1.8 µm). This study will facilitate the employment of O. alaskensis G20 in extreme pH environments, enhancing its effectiveness in optimizing bioremediation and anaerobic digestion processes. IMPORTANCE Sulfate-reducing bacteria (SRB) play essential roles in global sulfur and carbon cycling and are critical for bioremediation and anaerobic digestion processes. However, detailed studies on the genotypic and phenotypic responses of SRB under varying pH conditions are limited. This study addresses this gap by examining the pH-dependent genetic and metabolic adaptations of Oleidesulfovibrio alaskensis G20, revealing key mechanisms regulating hydrogenase and ATPase activities, cell division, and extracellular polymeric substance formation. These findings provide new insights into how SRB maintains pH homeostasis, showcasing their ability to survive and function in both acidic and alkaline environments. Furthermore, this study reveals critical genetic and phenotypic characteristics that will directly aid to engineer industrial effluent management systems, bioremediation, and dissolved heavy metal recovery. By elucidating the dynamic response of O. alaskensis G20 to varied pH environments, the research provides a foundation for enhancing the resilience and performance of SRB-based systems, paving the way for improved environmental and industrial applications.
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Affiliation(s)
- Priya Saxena
- Department of Chemical and Biological Engineering, South Dakota School of Mines and Technology, Rapid City, South Dakota, USA
- Data-Driven Material Discovery Center for Bioengineering Innovation, South Dakota School of Mines and Technology, Rapid City, South Dakota, USA
| | - Dipayan Samanta
- Department of Chemical and Biological Engineering, South Dakota School of Mines and Technology, Rapid City, South Dakota, USA
| | - Payal Thakur
- Department of Chemical and Biological Engineering, South Dakota School of Mines and Technology, Rapid City, South Dakota, USA
- Data-Driven Material Discovery Center for Bioengineering Innovation, South Dakota School of Mines and Technology, Rapid City, South Dakota, USA
| | - Kian Mau Goh
- Faculty of Science, Universiti Teknologi Malaysia, Johor, Malaysia
| | - Mahadevan Subramaniam
- Computer Science, College of Information Science and Technology, University of Nebraska Omaha, Omaha, Nebraska, USA
| | - Brent M Peyton
- Department of Chemical and Biological Engineering, Montana State University, Bozeman, Montana, USA
| | - Matthew Fields
- Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA
| | - Rajesh K Sani
- Department of Chemical and Biological Engineering, South Dakota School of Mines and Technology, Rapid City, South Dakota, USA
- Data-Driven Material Discovery Center for Bioengineering Innovation, South Dakota School of Mines and Technology, Rapid City, South Dakota, USA
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Thompson S, Ojo OR, Hoyles L, Winter J. Menadione reduces the expression of virulence- and colonization-associated genes in Helicobacter pylori. MICROBIOLOGY (READING, ENGLAND) 2025; 171. [PMID: 40072906 DOI: 10.1099/mic.0.001539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/14/2025]
Abstract
Novel treatment options are needed for the gastric pathogen Helicobacter pylori due to its increasing antibiotic resistance. The vitamin K analogue menadione has been extensively studied due to interest in its anti-bacterial and anti-cancer properties. Here, we investigated the effects of menadione on H. pylori growth, viability, antibiotic resistance, motility and gene expression using clinical isolates. The MIC of menadione was 313 µM for 11/13 isolates and 156 µM for 2/13 isolates. The minimum bactericidal concentrations were 1.25-2.5 mM, indicating that concentrations in the micromolar range were bacteriostatic rather than bactericidal. We were not able to experimentally evolve resistance to menadione in vitro. Sub-MIC menadione (16 µM for 24 h) did not significantly inhibit bacterial growth but significantly (P<0.05) changed the expression of 1291/1615 (79.9%) genes encoded by strain 322A. The expression of the virulence factor genes cagA and vacA was downregulated in the presence of sub-MIC menadione, while genes involved in stress responses were upregulated. Sub-MIC menadione significantly (P<0.0001) inhibited the motility of H. pylori, consistent with the predicted effects of the observed significant (P<0.05) downregulation of cheY, upregulation of rpoN and changes in the expression of flagellar assembly pathway genes seen in the transcriptomic analysis. Through in-depth interrogation of transcriptomic data, we concluded that sub-MIC menadione elicits a general stress response in H. pylori with survival in the stationary phase likely mediated by the upregulation of surE and rpoN. Sub-MIC menadione caused some modest increases in H. pylori susceptibility to antibiotics, but the effect was variable with strain and antibiotic type and did not reach statistical significance. Menadione (78 µM) was minimally cytotoxic to human gastric adenocarcinoma (AGS) cells after 4 h but caused a significant loss of cell viability after 24 h. Given its inhibitory effects on bacterial growth, motility and expression of virulence- and colonization-associated genes, menadione at low micromolar concentrations may have potential utility as a virulence-attenuating agent against H. pylori.
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Affiliation(s)
- Stephen Thompson
- School of Science and Technology, Nottingham Trent University, Nottingham, UK
| | - Omoyemi Rebecca Ojo
- School of Science and Technology, Nottingham Trent University, Nottingham, UK
| | - Lesley Hoyles
- School of Science and Technology, Nottingham Trent University, Nottingham, UK
| | - Jody Winter
- School of Science and Technology, Nottingham Trent University, Nottingham, UK
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Trautmann D, Suazo F, Torres K, Simón L. Antitumor Effects of Resveratrol Opposing Mechanisms of Helicobacter pylori in Gastric Cancer. Nutrients 2024; 16:2141. [PMID: 38999888 PMCID: PMC11243391 DOI: 10.3390/nu16132141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 07/02/2024] [Accepted: 07/02/2024] [Indexed: 07/14/2024] Open
Abstract
Gastric cancer is an aggressive and multifactorial disease. Helicobacter pylori (H. pylori) is identified as a significant etiological factor in gastric cancer. Although only a fraction of patients infected with H. pylori progresses to gastric cancer, bacterial infection is critical in the pathology and development of this malignancy. The pathogenic mechanisms of this bacterium involve the disruption of the gastric epithelial barrier and the induction of chronic inflammation, oxidative stress, angiogenesis and metastasis. Adherence molecules, virulence (CagA and VacA) and colonization (urease) factors are important in its pathogenicity. On the other hand, resveratrol is a natural polyphenol with anti-inflammatory and antioxidant properties. Resveratrol also inhibits cancer cell proliferation and angiogenesis, suggesting a role as a potential therapeutic agent against cancer. This review explores resveratrol as an alternative cancer treatment, particularly against H. pylori-induced gastric cancer, due to its ability to mitigate the pathogenic effects induced by bacterial infection. Resveratrol has shown efficacy in reducing the proliferation of gastric cancer cells in vitro and in vivo. Moreover, the synergistic effects of resveratrol with chemotherapy and radiotherapy underline its therapeutic potential. However, further research is needed to fully describe its efficacy and safety in treating gastric cancer.
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Affiliation(s)
- Daniela Trautmann
- Nutrition and Dietetic School, Universidad Finis Terrae, Santiago 7501015, Chile
| | - Francesca Suazo
- Nutrition and Dietetic School, Universidad Finis Terrae, Santiago 7501015, Chile
| | - Keila Torres
- Nutrition and Dietetic School, Universidad Finis Terrae, Santiago 7501015, Chile
- Department of Hematology and Oncology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile
| | - Layla Simón
- Nutrition and Dietetic School, Universidad Finis Terrae, Santiago 7501015, Chile
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Åberg A, Gideonsson P, Bhat A, Ghosh P, Arnqvist A. Molecular insights into the fine-tuning of pH-dependent ArsR-mediated regulation of the SabA adhesin in Helicobacter pylori. Nucleic Acids Res 2024; 52:5572-5595. [PMID: 38499492 PMCID: PMC11162790 DOI: 10.1093/nar/gkae188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 02/28/2024] [Accepted: 03/12/2024] [Indexed: 03/20/2024] Open
Abstract
Adaptation to variations in pH is crucial for the ability of Helicobacter pylori to persist in the human stomach. The acid responsive two-component system ArsRS, constitutes the global regulon that responds to acidic conditions, but molecular details of how transcription is affected by the ArsR response regulator remains poorly understood. Using a combination of DNA-binding studies, in vitro transcription assays, and H. pylori mutants, we demonstrate that phosphorylated ArsR (ArsR-P) forms an active protein complex that binds DNA with high specificity in order to affect transcription. Our data showed that DNA topology is key for DNA binding. We found that AT-rich DNA sequences direct ArsR-P to specific sites and that DNA-bending proteins are important for the effect of ArsR-P on transcription regulation. The repression of sabA transcription is mediated by ArsR-P with the support of Hup and is affected by simple sequence repeats located upstream of the sabA promoter. Here stochastic events clearly contribute to the fine-tuning of pH-dependent gene regulation. Our results reveal important molecular aspects for how ArsR-P acts to repress transcription in response to acidic conditions. Such transcriptional control likely mediates shifts in bacterial positioning in the gastric mucus layer.
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Affiliation(s)
- Anna Åberg
- Department of Medical Biochemistry and Biophysics, Umeå University, SE-90187 Umeå, Sweden
| | - Pär Gideonsson
- Department of Medical Biochemistry and Biophysics, Umeå University, SE-90187 Umeå, Sweden
| | - Abhayprasad Bhat
- Department of Medical Biochemistry and Biophysics, Umeå University, SE-90187 Umeå, Sweden
| | - Prachetash Ghosh
- Department of Medical Biochemistry and Biophysics, Umeå University, SE-90187 Umeå, Sweden
| | - Anna Arnqvist
- Department of Medical Biochemistry and Biophysics, Umeå University, SE-90187 Umeå, Sweden
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Vannini A, Pinatel E, Costantini PE, Pelliciari S, Roncarati D, Puccio S, De Bellis G, Scarlato V, Peano C, Danielli A. (Re)-definition of the holo- and apo-Fur direct regulons of Helicobacter pylori. J Mol Biol 2024; 436:168573. [PMID: 38626867 DOI: 10.1016/j.jmb.2024.168573] [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: 12/13/2023] [Revised: 04/09/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024]
Abstract
Iron homeostasis is a critical process for living organisms because this metal is an essential co-factor for fundamental biochemical activities, like energy production and detoxification, albeit its excess quickly leads to cell intoxication. The protein Fur (ferric uptake regulator) controls iron homeostasis in bacteria by switching from its apo- to holo-form as a function of the cytoplasmic level of ferrous ions, thereby modulating gene expression. The Helicobacter pylori HpFur protein has the rare ability to operate as a transcriptional commutator; apo- and holo-HpFur function as two different repressors with distinct DNA binding recognition properties for specific sets of target genes. Although the regulation of apo- and holo-HpFur in this bacterium has been extensively investigated, we propose a genome-wide redefinition of holo-HpFur direct regulon in H. pylori by integration of RNA-seq and ChIP-seq data, and a large extension of the apo-HpFur direct regulon. We show that in response to iron availability, new coding sequences, non-coding RNAs, toxin-antitoxin systems, and transcripts within open reading frames are directly regulated by apo- or holo-HpFur. These new targets and the more thorough validation and deeper characterization of those already known provide a complete and updated picture of the direct regulons of this two-faced transcriptional regulator.
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Affiliation(s)
- Andrea Vannini
- University of Bologna Department of Pharmacy and Biotechnology, Via Selmi 3, 40126 Bologna, Italy.
| | - Eva Pinatel
- Institute of Biomedical Technologies - National Research Council, Via Fratelli Cervi 93, 20054 Segrate (MI), Italy.
| | - Paolo Emidio Costantini
- University of Bologna Department of Pharmacy and Biotechnology, Via Selmi 3, 40126 Bologna, Italy.
| | - Simone Pelliciari
- Human Genetic Unit, Institute of Genetic and Cancer - University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
| | - Davide Roncarati
- University of Bologna Department of Pharmacy and Biotechnology, Via Selmi 3, 40126 Bologna, Italy.
| | - Simone Puccio
- Institute of Genetics and Biomedical Research, UoS Milan - National Research Council, Via Manzoni 113, 20089 Rozzano (MI), Italy; Humanitas Clinical and Research Center, Via Manzoni 56, 20089 Rozzano (MI), Italy.
| | - Gianluca De Bellis
- Institute of Biomedical Technologies - National Research Council, Via Fratelli Cervi 93, 20054 Segrate (MI), Italy.
| | - Vincenzo Scarlato
- University of Bologna Department of Pharmacy and Biotechnology, Via Selmi 3, 40126 Bologna, Italy.
| | - Clelia Peano
- Institute of Genetics and Biomedical Research, UoS Milan - National Research Council, Via Manzoni 113, 20089 Rozzano (MI), Italy; Human Technopole, Via Rita Levi Montalcini 1, 20157 Milan, Italy.
| | - Alberto Danielli
- University of Bologna Department of Pharmacy and Biotechnology, Via Selmi 3, 40126 Bologna, Italy.
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Zimmerman EH, Ramsey EL, Hunter KE, Villadelgado SM, Phillips CM, Shipman RT, Forsyth MH. The Helicobacter pylori methylome is acid-responsive due to regulation by the two-component system ArsRS and the type I DNA methyltransferase HsdM1 (HP0463). J Bacteriol 2024; 206:e0030923. [PMID: 38179929 PMCID: PMC10810217 DOI: 10.1128/jb.00309-23] [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: 09/23/2023] [Accepted: 12/14/2023] [Indexed: 01/06/2024] Open
Abstract
In addition to its role in genome protection, DNA methylation can regulate gene expression. In this study, we characterized the impact of acidity, phase variation, and the ArsRS TCS on the expression of the Type I m6A DNA methyltransferase HsdM1 (HP0463) of Helicobacter pylori 26695 and their subsequent effects on the methylome. Transcription of hsdM1 increases at least fourfold in the absence of the sensory histidine kinase ArsS, the major acid-sensing protein of H. pylori. hsdM1 exists in the phase-variable operon hsdR1-hsdM1. Phase-locking hsdR1 (HP0464), the restriction endonuclease gene, has significant impacts on the transcription of hsdM1. To determine the impacts of methyltransferase transcription patterns on the methylome, we conducted methylome sequencing on samples cultured at pH 7 or pH 5. We found differentially methylated motifs between these growth conditions and that deletions of arsS and/or hsdM1 interfere with the epigenetic acid response. Deletion of arsS leads to altered activity of HsdM1 and multiple other methyltransferases under both pH conditions indicating that the ArsRS TCS, in addition to direct effects on regulon transcription during acid acclimation, may also indirectly impact gene expression via regulation of the methylome. We determined the target motif of HsdM1 (HP0463) to be the complementary bipartite sequence pair 5'-TCAm6AVN6TGY-3' and 3'-AGTN6GAm6ACA-5'. This complex regulation of DNA methyltransferases, and thus differential methylation patterns, may have implications for the decades-long persistent infection by H. pylori. IMPORTANCE This study expands the possibilities for complex, epigenomic regulation in Helicobacter pylori. We demonstrate that the H. pylori methylome is plastic and acid sensitive via the two-component system ArsRS and the DNA methyltransferase HsdM1. The control of a methyltransferase by ArsRS may allow for a layered response to changing acidity. Likely, an early response whereby ArsR~P affects regulon expression, including the methyltransferase hsdM1. Then, a somewhat later effect as the altered methylome, due to altered HsdM1 expression, subsequently alters the expression of other genes involved in acclimation. The intermediate methylation of certain motifs supports the hypothesis that methyltransferases play a regulatory role. Untangling this additional web of regulation could play a key role in understanding H. pylori colonization and persistence.
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Affiliation(s)
| | - Erin L. Ramsey
- Department of Biology, William & Mary, Williamsburg, Virginia, USA
| | | | | | | | - Ryan T. Shipman
- Department of Biology, William & Mary, Williamsburg, Virginia, USA
| | - Mark H. Forsyth
- Department of Biology, William & Mary, Williamsburg, Virginia, USA
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7
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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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Al-Fakhrany OM, Elekhnawy E. Helicobacter pylori in the post-antibiotics era: from virulence factors to new drug targets and therapeutic agents. Arch Microbiol 2023; 205:301. [PMID: 37550555 PMCID: PMC10406680 DOI: 10.1007/s00203-023-03639-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 07/16/2023] [Accepted: 07/20/2023] [Indexed: 08/09/2023]
Abstract
Helicobacter pylori is considered one of the most prevalent human pathogenic microbes globally. It is the main cause of a number of gastrointestinal ailments, including peptic and duodenal ulcers, and gastric tumors with high mortality rates. Thus, eradication of H. pylori is necessary to prevent gastric cancer. Still, the rise in antibiotic resistance is the most important challenge for eradication strategies. Better consideration of H. pylori virulence factors, pathogenesis, and resistance is required for better eradication rates and, thus, prevention of gastrointestinal malignancy. This article is aimed to show the role of virulence factors of H. pylori. Some are involved in its survival in the harsh environment of the human gastric lumen, and others are related to pathogenesis and the infection process. Furthermore, this work has highlighted the recent advancement in H. pylori treatment, as well as antibiotic resistance as a main challenge in H. pylori eradication. Also, we tried to provide an updated summary of the evolving H. pylori control strategies and the potential alternative drugs to fight this lethal resistant pathogen. Recent studies have focused on evaluating the efficacy of alternative regimens (such as sequential, hybrid, concomitant treatment, vonoprazan (VPZ)-based triple therapy, high-dose PPI-amoxicillin dual therapy, probiotics augmented triple therapy, or in combination with BQT) in the effective eradication of H. pylori. Thus, innovating new anti-H. pylori drugs and establishing H. pylori databanks are upcoming necessities in the near future.
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Affiliation(s)
- Omnia Momtaz Al-Fakhrany
- Pharmaceutical Microbiology Department, Faculty of Pharmacy, Tanta University, Tanta, 31527 Egypt
| | - Engy Elekhnawy
- Pharmaceutical Microbiology Department, Faculty of Pharmacy, Tanta University, Tanta, 31527 Egypt
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Tao H, Meng F, Zhou Y, Fan J, Liu J, Han Y, Sun BB, Wang G. Transcriptomic and Functional Approaches Unveil the Role of tmRNA in Zinc Acetate Mediated Levofloxacin Sensitivity in Helicobacter pylori. Microbiol Spectr 2022; 10:e0115222. [PMID: 36354329 PMCID: PMC9769675 DOI: 10.1128/spectrum.01152-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 10/17/2022] [Indexed: 11/12/2022] Open
Abstract
Rapid increase in resistance of Helicobacter pylori (H. pylori) has hindered antibiotics-based eradication efforts worldwide and raises the need for additional approaches. Here, we investigate the role of zinc-based compounds in inhibiting H. pylori growth and modulating antibiotic sensitivities, interrogate their downstream transcriptomic changes, and highlight the potential mechanism driving the observed effects. We showed that zinc acetate inhibited H. pylori growth and increased H. pylori sensitivity to levofloxacin. Transcriptomic profiling showed distinct gene expression patterns between zinc acetate treated groups versus controls. In particular, we independently replicated the association between zinc acetate treatment and increased ssrA expression. Knockdown of ssrA restored levofloxacin resistance to levels of the control group. In this study, we first demonstrated the role of zinc acetate in H. pylori growth and antibiotic sensitivities. Additionally, we explored the transcriptomic perturbations of zinc acetate followed by functional knockdown follow-up of differentially expressed ssrA, highlighting the role of tmRNA and trans-translation in H. pylori levofloxacin resistance. Our results provide alternative and complementary strategies for H. pylori treatment and shed light on the underlying mechanisms driving these effects. IMPORTANCE Helicobacter pylori (H. pylori) eradication plays an important role in gastric cancer prevention, but the antimicrobial resistance of H. pylori is fast becoming a growing concern. In this study, we investigated the role of zinc acetate in inhibiting H. pylori growth and modulating antibiotic sensitivities in vitro. Additionally, we explored the transcriptomic perturbations of zinc acetate followed by functional knockdown follow-up of differentially expressed ssrA, highlighting the role of tmRNA and trans-translation in H. pylori levofloxacin resistance. Our results open up a new horizon for the treatment of antibiotic-resistant H. pylori.
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Affiliation(s)
- Hongjin Tao
- Department of Gastroenterology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China
- Medical School of Chinese PLA, Beijing, People’s Republic of China
| | - Fansen Meng
- Department of Gastroenterology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Yu Zhou
- Department of Laboratory Medicine, Second Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Jiao Fan
- Institute of Geriatrics, National Clinical Research Center of Geriatrics Disease, Second Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Jing Liu
- Institute of Geriatrics, National Clinical Research Center of Geriatrics Disease, Second Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Yingjie Han
- Department of Oncology, Fifth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Benjamin B. Sun
- MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Gangshi Wang
- Department of Gastroenterology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China
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Marmion M, Macori G, Ferone M, Whyte P, Scannell A. Survive and thrive: Control mechanisms that facilitate bacterial adaptation to survive manufacturing-related stress. Int J Food Microbiol 2022; 368:109612. [DOI: 10.1016/j.ijfoodmicro.2022.109612] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 02/21/2022] [Accepted: 03/02/2022] [Indexed: 10/18/2022]
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Sharndama HC, Mba IE. Helicobacter pylori: an up-to-date overview on the virulence and pathogenesis mechanisms. Braz J Microbiol 2022; 53:33-50. [PMID: 34988937 PMCID: PMC8731681 DOI: 10.1007/s42770-021-00675-0] [Citation(s) in RCA: 83] [Impact Index Per Article: 27.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 12/24/2021] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori is an organism associated with ulcer disease and gastric cancer. The latter is one of the most prevalent malignancies and currently the fourth major cause of cancer-related deaths globally. The pathogen infects about 50% of the world population, and currently, no treatment ensures its total elimination. There has been an increase in our understanding of the pathophysiology and pathogenesis mechanisms of H. pylori over the years. H. pylori can induce several genetic alterations, express numerous virulence factors, and trigger diverse adaptive mechanisms during its adherence and colonization. For successful colonization and infection establishment, several effector proteins/toxins are released by the organism. Evidence is also available reporting spiral to coccoid transition as a unique tactic H. pylori uses to survive in the host's gastrointestinal tract (GIT). Thus, the virulence and pathogenicity of H. pylori are under the control of complex interplay between the virulence factors, host, and environmental factors. Expounding the role of the various virulence factors in H. pylori pathogenesis and clinical outcomes is crucial for vaccine development and in providing and developing a more effective therapeutic intervention. Here we critically reflect on H. pylori infection and delineate what is currently known about the virulence and pathogenesis mechanisms of H. pylori.
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Affiliation(s)
| | - Ifeanyi Elibe Mba
- Department of Microbiology, University of Nigeria, Nsukka, Enugu, Nigeria.
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12
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The changing microbiome of poultry meat; from farm to fridge. Food Microbiol 2021; 99:103823. [PMID: 34119108 DOI: 10.1016/j.fm.2021.103823] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 04/24/2021] [Accepted: 04/27/2021] [Indexed: 11/20/2022]
Abstract
Chickens play host to a diverse community of microorganisms which constitute the microflora of the live bird. Factors such as diet, genetics and immune system activity affect this complex population within the bird, while external influences including weather and exposure to other animals alter the development of the microbiome. Bacteria from these settings including Campylobacter and Salmonella play an important role in the quality and safety of end-products from these birds. Further steps, including washing and chilling, within the production cycle aim to control the proliferation of these microbes as well as those which cause product spoilage. These steps impose specific selective pressures upon the microflora of the meat product. Within the next decade, it is forecast that poultry meat, particularly chicken will become the most consumed meat globally. However, as poultry meat is a frequently cited reservoir of zoonotic disease, understanding the development of its microflora is key to controlling the proliferation of important spoilage and pathogenic bacterial groups present on the bird. Whilst several excellent reviews exist detailing the microbiome of poultry during primary production, others focus on fate of important poultry pathogens such as Campylobacter and Salmonella spp. At farm and retail level, and yet others describe the evolution of spoilage microbes during spoilage. This review seeks to provide the poultry industry and research scientists unfamiliar with food technology process with a holistic overview of the key changes to the microflora of broiler chickens at each stage of the production and retail cycle.
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13
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Zhang X, Zhou D, Bai H, Liu Q, Xiao XL, Yu YG. Comparative transcriptome analysis of virulence genes of enterohemorrhagic Escherichia coli O157:H7 to acid stress. FOOD BIOTECHNOL 2021. [DOI: 10.1080/08905436.2021.1908345] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Affiliation(s)
- Xiaowei Zhang
- School of Food Science and Engineering, South China University of Technology, Guangzhou City, Guangdong Province, China
| | - Donggen Zhou
- Ningbo International Travel Healthcare Center, Ningbo City, Haishu District, China
| | - Hong Bai
- School of Food Science and Engineering, South China University of Technology, Guangzhou City, Guangdong Province, China
| | - Qijun Liu
- School of Food Science and Engineering, South China University of Technology, Guangzhou City, Guangdong Province, China
| | - Xing-Long Xiao
- School of Food Science and Engineering, South China University of Technology, Guangzhou City, Guangdong Province, China
| | - Yi-Gang Yu
- School of Food Science and Engineering, South China University of Technology, Guangzhou City, Guangdong Province, China
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14
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Delineation of the pH-Responsive Regulon Controlled by the Helicobacter pylori ArsRS Two-Component System. Infect Immun 2021; 89:IAI.00597-20. [PMID: 33526561 DOI: 10.1128/iai.00597-20] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 01/09/2021] [Indexed: 12/22/2022] Open
Abstract
Helicobacter pylori encounters a wide range of pH within the human stomach. In a comparison of H. pylori cultured in vitro under neutral or acidic conditions, about 15% of genes are differentially expressed, and corresponding changes are detectable for many of the encoded proteins. The ArsRS two-component system (TCS), comprised of the sensor kinase ArsS and its cognate response regulator ArsR, has an important role in mediating pH-responsive changes in H. pylori gene expression. In this study, we sought to delineate the pH-responsive ArsRS regulon and further define the role of ArsR in pH-responsive gene expression. We compared H. pylori strains containing an intact ArsRS system with an arsS null mutant or strains containing site-specific mutations of a conserved aspartate residue (D52) in ArsR, which is phosphorylated in response to signals relayed by the cognate sensor kinase ArsS. We identified 178 genes that were pH-responsive in strains containing an intact ArsRS system but not in ΔarsS or arsR mutants. These constituents of the pH-responsive ArsRS regulon include genes involved in acid acclimatization (ureAB, amidases), oxidative stress responses (katA, sodB), transcriptional regulation related to iron or nickel homeostasis (fur, nikR), and genes encoding outer membrane proteins (including sabA, alpA, alpB, hopD [labA], and horA). When comparing H. pylori strains containing an intact ArsRS TCS with arsRS mutants, each cultured at neutral pH, relatively few genes are differentially expressed. Collectively, these data suggest that ArsRS-mediated gene regulation has an important role in H. pylori adaptation to changing pH conditions.
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15
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Xu X, Chen J, Huang X, Feng S, Zhang X, She F, Wen Y. The Role of a Dipeptide Transporter in the Virulence of Human Pathogen, Helicobacter pylori. Front Microbiol 2021; 12:633166. [PMID: 33732225 PMCID: PMC7959749 DOI: 10.3389/fmicb.2021.633166] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 02/05/2021] [Indexed: 12/16/2022] Open
Abstract
Helicobacter pylori harbors a dipeptide (Dpp) transporter consisting of a substrate-binding protein (DppA), two permeases (DppB and C), and two ATPases (DppD and F). The Dpp transporter is responsible for the transportation of dipeptides and short peptides. We found that its expression is important for the growth of H. pylori. To understand the role of the Dpp transporter in the pathogenesis of H. pylori, the expression of virulence factors and H. pylori-induced IL-8 production were investigated in H. pylori wild-type and isogenic H. pylori Dpp transporter mutants. We found that expression of CagA was downregulated, while expression of type 4 secretion system (T4SS) components was upregulated in Dpp transporter mutants. The DppA mutant strain expressed higher levels of outer membrane proteins (OMPs), including BabA, HopZ, OipA, and SabA, and showed a higher adhesion level to gastric epithelial AGS cells compared with the H. pylori 26695 wild-type strain. After infection of AGS cells, H. pylori ΔdppA induced a higher level of NF-κB activation and IL-8 production compared with wild-type. These results suggested that in addition to supporting the growth of H. pylori, the Dpp transporter causes bacteria to alter the expression of virulence factors and reduces H. pylori-induced NF-κB activation and IL-8 production in gastric epithelial cells.
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Affiliation(s)
- Xiaohong Xu
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China.,Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China.,Fujian Medical University Union Hospital, Fuzhou, China
| | - Junwei Chen
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China.,Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Xiaoxing Huang
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China.,Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Shunhang Feng
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China.,Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Xiaoyan Zhang
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China.,Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Feifei She
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China.,Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Yancheng Wen
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China.,Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
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16
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Reshetnyak VI, Burmistrov AI, Maev IV. Helicobacter pylori: Commensal, symbiont or pathogen? World J Gastroenterol 2021; 27:545-560. [PMID: 33642828 PMCID: PMC7901052 DOI: 10.3748/wjg.v27.i7.545] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 12/28/2020] [Accepted: 01/21/2021] [Indexed: 02/06/2023] Open
Abstract
This review considers the data on Helicobacter pylori (H. pylori), which have been accumulated over 40 years since its description as an etiological factor in gastrointestinal diseases. The majority of modern publications are devoted to the study of the pathogenic properties of the microorganism in the development of chronic gastritis, peptic ulcer disease, and gastric cancer, as well as methods for its eradication. However, in recent years, there have been more and more studies which have suggested that H. pylori has a beneficial, or potentially positive, effect on the human body. The authors have attempted to objectively analyze the information accumulated in the literature on H. pylori. Some studies consider it as one of the recently identified human bacterial pathogens, and special attention is paid to the evidence suggesting that it is probably part of the composition of the human microbiome as a commensal (commensal from French to English is a table companion) or even a symbiont. The presented data discussing the presence or absence of the effect of H. pylori on human health suggest that there is an apparent ambiguity of the problem. The re-assessment of the data available on H. pylori infection is important in order to answer the question of whether it is necessary to create a program of mass H. pylori eradication or to apply a more personalized approach to treating patients with H. pylori-associated gastrointestinal diseases and to perform eradication therapy.
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Affiliation(s)
- Vasiliy Ivanovich Reshetnyak
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
| | - Alexandr Igorevich Burmistrov
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
| | - Igor Veniaminovich Maev
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
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17
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Fisher L, Fisher A, Smith PN. Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review). J Clin Med 2020; 9:E3253. [PMID: 33053671 PMCID: PMC7600664 DOI: 10.3390/jcm9103253] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 09/28/2020] [Accepted: 10/07/2020] [Indexed: 02/06/2023] Open
Abstract
Osteoporosis (OP) and osteoporotic fractures (OFs) are common multifactorial and heterogenic disorders of increasing incidence. Helicobacter pylori (H.p.) colonizes the stomach approximately in half of the world's population, causes gastroduodenal diseases and is prevalent in numerous extra-digestive diseases known to be associated with OP/OF. The studies regarding relationship between H.p. infection (HPI) and OP/OFs are inconsistent. The current review summarizes the relevant literature on the potential role of HPI in OP, falls and OFs and highlights the reasons for controversies in the publications. In the first section, after a brief overview of HPI biological features, we analyze the studies evaluating the association of HPI and bone status. The second part includes data on the prevalence of OP/OFs in HPI-induced gastroduodenal diseases (peptic ulcer, chronic/atrophic gastritis and cancer) and the effects of acid-suppressive drugs. In the next section, we discuss the possible contribution of HPI-associated extra-digestive diseases and medications to OP/OF, focusing on conditions affecting both bone homeostasis and predisposing to falls. In the last section, we describe clinical implications of accumulated data on HPI as a co-factor of OP/OF and present a feasible five-step algorithm for OP/OF risk assessment and management in regard to HPI, emphasizing the importance of an integrative (but differentiated) holistic approach. Increased awareness about the consequences of HPI linked to OP/OF can aid early detection and management. Further research on the HPI-OP/OF relationship is needed to close current knowledge gaps and improve clinical management of both OP/OF and HPI-related disorders.
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Affiliation(s)
- Leon Fisher
- Department of Gastroenterology, Frankston Hospital, Peninsula Health, Melbourne 3199, Australia
| | - Alexander Fisher
- Department of Geriatric Medicine, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Department of Orthopedic Surgery, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Australian National University Medical School, Canberra 2605, Australia
| | - Paul N Smith
- Department of Orthopedic Surgery, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Australian National University Medical School, Canberra 2605, Australia
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18
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Pathways of Gastric Carcinogenesis, Helicobacter pylori Virulence and Interactions with Antioxidant Systems, Vitamin C and Phytochemicals. Int J Mol Sci 2020; 21:ijms21176451. [PMID: 32899442 PMCID: PMC7503565 DOI: 10.3390/ijms21176451] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 08/21/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori is a class one carcinogen which causes chronic atrophic gastritis, gastric intestinal metaplasia, dysplasia and adenocarcinoma. The mechanisms by which H. pylori interacts with other risk and protective factors, particularly vitamin C in gastric carcinogenesis are complex. Gastric carcinogenesis includes metabolic, environmental, epigenetic, genomic, infective, inflammatory and oncogenic pathways. The molecular classification of gastric cancer subtypes has revolutionized the understanding of gastric carcinogenesis. This includes the tumour microenvironment, germline mutations, and the role of Helicobacter pylori bacteria, Epstein Barr virus and epigenetics in somatic mutations. There is evidence that ascorbic acid, phytochemicals and endogenous antioxidant systems can modify the risk of gastric cancer. Gastric juice ascorbate levels depend on dietary intake of ascorbic acid but can also be decreased by H. pylori infection, H. pylori CagA secretion, tobacco smoking, achlorhydria and chronic atrophic gastritis. Ascorbic acid may be protective against gastric cancer by its antioxidant effect in gastric cytoprotection, regenerating active vitamin E and glutathione, inhibiting endogenous N-nitrosation, reducing toxic effects of ingested nitrosodimethylamines and heterocyclic amines, and preventing H. pylori infection. The effectiveness of such cytoprotection is related to H. pylori strain virulence, particularly CagA expression. The role of vitamin C in epigenetic reprogramming in gastric cancer is still evolving. Other factors in conjunction with vitamin C also play a role in gastric carcinogenesis. Eradication of H. pylori may lead to recovery of vitamin C secretion by gastric epithelium and enable regression of premalignant gastric lesions, thereby interrupting the Correa cascade of gastric carcinogenesis.
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19
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Pohl D, Keller PM, Bordier V, Wagner K. Review of current diagnostic methods and advances in Helicobacter pylori diagnostics in the era of next generation sequencing. World J Gastroenterol 2019; 25:4629-4660. [PMID: 31528091 PMCID: PMC6718044 DOI: 10.3748/wjg.v25.i32.4629] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 06/25/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is highly prevalent in the human population and may lead to severe gastrointestinal pathology including gastric and duodenal ulcers, mucosa associated tissue lymphoma and gastric adenocarcinoma. In recent years, an alarming increase in antimicrobial resistance and subsequently failing empiric H. pylori eradication therapies have been noted worldwide, also in many European countries. Therefore, rapid and accurate determination of H. pylori’s antibiotic susceptibility prior to the administration of eradication regimens becomes ever more important. Traditionally, detection of H. pylori and its antimicrobial resistance is done by culture and phenotypic drug susceptibility testing that are cumbersome with a long turn-around-time. Recent advances in diagnostics provide new tools, like real-time polymerase chain reaction (PCR) and line probe assays, to diagnose H. pylori infection and antimicrobial resistance to certain antibiotics, directly from clinical specimens. Moreover, high-throughput whole genome sequencing technologies allow the rapid analysis of the pathogen’s genome, thereby allowing identification of resistance mutations and associated antibiotic resistance. In the first part of this review, we will give an overview on currently available diagnostic methods for detection of H. pylori and its drug resistance and their implementation in H. pylori management. The second part of the review focusses on the use of next generation sequencing technology in H. pylori research. To this end, we conducted a literature search for original research articles in English using the terms “Helicobacter”, “transcriptomic”, “transcriptome”, “next generation sequencing” and “whole genome sequencing”. This review is aimed to bridge the gap between current diagnostic practice (histology, rapid urease test, H. pylori culture, PCR and line probe assays) and new sequencing technologies and their potential implementation in diagnostic laboratory settings in order to complement the currently recommended H. pylori management guidelines and subsequently improve public health.
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Affiliation(s)
- Daniel Pohl
- Division of Gastroenterology, University Hospital of Zurich, Zurich 8006, Switzerland
| | - Peter M Keller
- Institute for Infectious Diseases, University of Bern, Bern 3010, Switzerland
| | - Valentine Bordier
- Division of Gastroenterology, University Hospital of Zurich, Zurich 8006, Switzerland
| | - Karoline Wagner
- Institute of Medical Microbiology, University of Zurich, Zurich 8006, Switzerland
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20
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Maxim R, Pleşa A, Stanciu C, Gîrleanu I, Moraru E, Trifan A. Helicobacter pylori prevalence and risk factors among children with celiac disease. THE TURKISH JOURNAL OF GASTROENTEROLOGY : THE OFFICIAL JOURNAL OF TURKISH SOCIETY OF GASTROENTEROLOGY 2019; 30:284-289. [PMID: 30460898 PMCID: PMC6428505 DOI: 10.5152/tjg.2018.18181] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND/AIMS The relationship between Helicobacter pylori and celiac disease (CD) remains controversial. The aim of this study was to assess the prevalence and risk factors for H. pylori infection among children diagnosed with CD. MATERIALS AND METHODS This study included 70 patients diagnosed with CD at a tertiary referral center in Romania. Age, gender, and indicators of environmental conditions were evaluated via interviews with the children's caretakers. A multivariable logistic regression analysis was performed to identify the independent predictors for H. pylori infection. RESULTS Of the 70 patients, 37 (52.9%) were females, and the mean age was 4.04±3.26 years. H. pylori infection was diagnosed in 23 (32.8%) patients, of whom 12 (52.1%) were females, and the mean age was 6.2±4.5 years. Of the total number of children with CD and H. pylori infection, 18 (78.2%) had milder forms of enteropathy (Marsh I-II), whereas the remaining 5 (21.7%) had villous atrophy compared to the other 47 (67.2%) patients who were negative for H. pylori-infection and showed more severe intestinal damage. The development of H. pylori infection was independently related to children with one parent only [odd ratio (OR), 9.04; 95% confidence interval (CI), 1.29-62.89; p<0.001], living in houses without sanitary facilities (OR, 3.88; 95% CI, 1.27-14.22; p=0.016), belonging to low-income families (OR, 8.52; 95% CI, 2.52-71.39; p=0.002), and of parents with a prior history of gastritis (OR, 2.68; 95% CI, 1.49-14.50; p=0.004). CONCLUSION Children with CD and H. pylori infection had milder forms of enteropathy compared to children who are negative for H. pylori, suggesting that H. pylori infection may confer some protection against the development of severe degrees of villous atrophy.
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Affiliation(s)
- Roxana Maxim
- Institute of Gastroenterology and Hepatology, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
| | - Alina Pleşa
- Institute of Gastroenterology and Hepatology, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
| | - Carol Stanciu
- Institute of Gastroenterology and Hepatology, FRCP, Iasi, Romania
| | - Irina Gîrleanu
- Institute of Gastroenterology and Hepatology, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
| | - Evelina Moraru
- Institute of Gastroenterology and Hepatology, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
| | - Anca Trifan
- Institute of Gastroenterology and Hepatology, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
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