scholarly journals Temporin-SHa and Its Analogs as Potential Candidates for the Treatment of Helicobacter pylori

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 598 ◽  
Author(s):  
Hamza Olleik ◽  
Elias Baydoun ◽  
Josette Perrier ◽  
Akram Hijazi ◽  
Josette Raymond ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Antibacterial Activity ◽  
Antibacterial Effect ◽  
Good Alternative ◽  
Resistant Bacteria ◽  
Gastric Cells ◽  
Resistant Strains ◽  
H Pylori ◽  
Conventional Antibiotics

Helicobacterpylori is one of the most prevalent pathogens colonizing 50% of the world’s population and causing gastritis and gastric cancer. Even with triple and quadruple antibiotic therapies, H. pylori shows increased prevalence of resistance to conventional antibiotics and treatment failure. Due to their pore-forming activity, antimicrobial peptides (AMP) are considered as a good alternative to conventional antibiotics, particularly in the case of resistant bacteria. In this study, temporin-SHa (a frog AMP) and its analogs obtained by Gly to Ala substitutions were tested against H. pylori. Results showed differences in the antibacterial activity and toxicity of the peptides in relation to the number and position of D-Ala substitution. Temporin-SHa and its analog NST1 were identified as the best molecules, both peptides being active on clinical resistant strains, killing 90–100% of bacteria in less than 1 h and showing low to no toxicity against human gastric cells and tissue. Importantly, the presence of gastric mucins did not prevent the antibacterial effect of temporin-SHa and NST1, NST1 being in addition resistant to pepsin. Taken together, our results demonstrated that temporin-SHa and its analog NST1 could be considered as potential candidates to treat H. pylori, particularly in the case of resistant strains.

scholarly journals In VitroInhibition ofHelicobacter pyloriGrowth by Redox Cycling Phenylaminojuglones

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Julio Benites ◽  
Héctor Toledo ◽  
Felipe Salas ◽  
Angélica Guerrero ◽  
David Rios ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Antibacterial Activity ◽  
Active Compound ◽  
Metabolic Pathways ◽  
Growth Inhibitor ◽  
Growth Inhibitors ◽  
Design Synthesis ◽  
H Pylori

Infection byHelicobacter pyloriincreases 10 times the risk of developing gastric cancer. Juglone, a natural occurring 1,4-naphthoquinone, preventsH. pylorigrowth by interfering with some of its critical metabolic pathways. Here, we report the design, synthesis, andin vitroevaluation of a series of juglone derivatives, namely, 2/3-phenylaminojuglones, as potentialH. pylorigrowth inhibitors. Results show that 5 out of 12 phenylaminojuglones (at 1.5 μg/mL) were 1.5–2.2-fold more active than juglone. Interestingly, most of the phenylaminojuglones (10 out of 12) were 1.1–2.8 fold more active than metronidazole, a knownH. pylorigrowth inhibitor. The most active compound, namely, 2-((3,4,5-trimethoxyphenyl)amino)-5-hydroxynaphthalene-1,4-dione 7, showed significant higher halo of growth inhibitions (HGI = 32.25 mm) to that of juglone and metronidazole (HGI = 14.50 and 11.67 mm). Structural activity relationships of the series suggest that the nature and location of the nitrogen substituents in the juglone scaffold, likely due in part to their redox potential, may influence the antibacterial activity of the series.

scholarly journals In Vitro Activity of a Novel Antimicrobial Agent, TG44, for Treatment of Helicobacter pylori Infection

2006 ◽  
Vol 50 (9) ◽  
pp. 3062-3069 ◽  
Author(s):  
Osamu Kamoda ◽  
Kinsei Anzai ◽  
Jun-ichi Mizoguchi ◽  
Masatoshi Shiojiri ◽  
Toshiharu Yanagi ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibacterial Activity ◽  
Bactericidal Activity ◽  
Structural Formula ◽  
Therapeutic Modalities ◽  
Resistant Strains ◽  
H Pylori ◽  
Ph Range ◽  
Drug Resistant Strains

ABSTRACT Due to concerns about the current therapeutic modalities for Helicobacter pylori infection, e.g., the increased emergence of drug-resistant strains and the adverse reactions of drugs currently administered, there is a need to develop an anti-H. pylori agent with higher efficacy and less toxicity. The antibacterial activity of TG44, an anti-H. pylori agent with a novel structural formula, against 54 clinical isolates of H. pylori was examined and compared with those of amoxicillin (AMX), clarithromycin (CLR), and metronidazole (MNZ). Consequently, TG44 inhibited the growth of H. pylori in an MIC range of 0.0625 to 1 μg/ml. The MIC ranges of AMX, CLR, and MNZ were 0.0078 to 8 μg/ml, 0.0156 to 64 μg/ml, and 2 to 128 μg/ml, respectively. The antibacterial activity of TG44 against AMX-, CLR-, and MNZ-resistant strains was nearly comparable to that against drug-susceptible ones. In a pH range of 3 to 7, TG44 at 3.13 to 12.5 μg/ml exhibited potent bactericidal activity against H. pylori in the stationary phase of growth as early as 1 h after treatment began, in contrast to AMX, which showed no bactericidal activity at concentrations of up to 50 μg/ml at the same time point of treatment. TG44 at 25 μg/ml exhibited no antibacterial activity against 13 strains of aerobic bacteria, suggesting that its antibacterial activity against H. pylori is potent and highly specific. The present study indicated that TG44 possesses antibacterial activity which manifests quickly and is potentially useful for eradicating not only the antibiotic-susceptible but also the antibiotic-resistant strains of H. pylori by monotherapy.

scholarly journals Nanomechanical Hallmarks of Helicobacter pylori Infection in Pediatric Patients

2021 ◽  
Vol 22 (11) ◽  
pp. 5624
Author(s):  
Piotr Deptuła ◽  
Łukasz Suprewicz ◽  
Tamara Daniluk ◽  
Andrzej Namiot ◽  
Sylwia Joanna Chmielewska ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mechanical Properties ◽  
Helicobacter Pylori ◽  
Mechanical Response ◽  
Cellular Level ◽  
Cancer Development ◽  
Tissue Samples ◽  
Diagnostic Measures ◽  
Gastric Cells ◽  
H Pylori

Background: the molecular mechanism of gastric cancer development related to Helicobacter pylori (H. pylori) infection has not been fully understood, and further studies are still needed. Information regarding nanomechanical aspects of pathophysiological events that occur during H. pylori infection can be crucial in the development of new prevention, treatment, and diagnostic measures against clinical consequences associated with H. pylori infection, including gastric ulcer, duodenal ulcer, and gastric cancer. Methods: in this study, we assessed mechanical properties of children’s healthy and H. pylori positive stomach tissues and the mechanical response of human gastric cells exposed to heat-treated H. pylori cells using atomic force microscopy (AFM NanoWizard 4 BioScience JPK Instruments Bruker). Elastic modulus (i.e., the Young’s modulus) was derived from the Hertz–Sneddon model applied to force-indentation curves. Human tissue samples were evaluated using rapid urease tests to identify H. pylori positive samples, and the presence of H. pylori cells in those samples was confirmed using immunohistopathological staining. Results and conclusion: collected data suggest that nanomechanical properties of infected tissue might be considered as markers indicated H. pylori presence since infected tissues are softer than uninfected ones. At the cellular level, this mechanical response is at least partially mediated by cell cytoskeleton remodeling indicating that gastric cells are able to tune their mechanical properties when subjected to the presence of H. pylori products. Persistent fluctuations of tissue mechanical properties in response to H. pylori infection might, in the long-term, promote induction of cancer development.

Hydrotalcite Can Prevent the Damaging Effects of Helicobacter Pylori on Gastric Epithelial Cells

2018 ◽  
Vol 24 (3) ◽  
pp. 277-283 ◽  
Author(s):  
Shi Yanyan ◽  
Guo Yanlei ◽  
Zhang Ting ◽  
Ding Shigang
Keyword(s):  
Electron Microscopy ◽  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Cell Line ◽  
Cell Apoptosis ◽  
Gastric Cancer Cell Line ◽  
Gastric Epithelial Cells ◽  
Gastric Cells ◽  
H Pylori

AbstractBackground: Helicobacter pylori is a major cause of gastric diseases including gastric cancer. This study was aimed to explore whether hydrotalcite can inhibit H. pylori infection of gastric epithelial cells. Methods: the gastric epithelial cell line GES-1 and the gastric cancer cell line BGC823 were infected with H. pylori at multiplicities of infections (MOIs) of 50:1 and 100:1. Hydrotalcite was added to cell cultures. Cell apoptosis and cell cycle analysis were performed to measure the situation of cell growth. The main changes of cell ultrastructure were observed by transmission electron microscopy. H. pylori cell adhesion was observed by scanning electron microscopy. Results: hydrotalcite could significantly inhibit cell apoptosis of GES-1 and cell proliferation of BGC823 induced by H. pylori infection at an MOI of 50:1. Hydrotalcite treatment protected gastric cells from H. pylori infection, and H. pylori adhesion to gastric cells was reduced. However, hydrotalcite could not reverse damage induced by H. pylori infection at an MOI of 100:1. Conclusion: hydrotalcite can protect gastric cells from H. pylori infection when cell damage is not serious. It can weaken the damage of cells induced by H. pylori and decrease H. pylori adhesion to gastric cells.

scholarly journals A Novel Role for Helicobacter pylori Gamma-Glutamyltranspeptidase in Regulating Autophagy and Bacterial Internalization in Human Gastric Cells

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 801 ◽  
Author(s):  
Jimena Bravo ◽  
Paula Díaz ◽  
Alejandro H. Corvalán ◽  
Andrew F.G. Quest
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Virulence Factor ◽  
Bacterial Infections ◽  
Membrane Integrity ◽  
Autophagic Flux ◽  
Ags Cells ◽  
Gastric Cells ◽  
H Pylori

The risk of developing gastric cancer is strongly linked to Helicobacter pylori (H. pylori) infection. Alternatively, autophagy is a conserved response that is important in cellular homeostasis and provides protection against bacterial infections. Although H. pylori is typically considered an extracellular bacterium, several reports indicate that it internalizes, possibly to avoid exposure to antibiotics. Mechanisms by which H. pylori manipulates host cell autophagic processes remain unclear and, importantly, none of the available studies consider a role for the secreted H. pylori virulence factor gamma-glutamyltranspeptidase (HpGGT) in this context. Here, we identify HpGGT as a novel autophagy inhibitor in gastric cells. Our experiments revealed that deletion of HpGGT increased autophagic flux following H. pylori infection of AGS and GES-1 gastric cells. In AGS cells, HpGGT disrupted the late stages of autophagy by preventing degradation in lysosomes without affecting lysosomal acidification. Specifically, HpGGT impaired autophagic flux by disrupting lysosomal membrane integrity, which leads to a decrease in lysosomal cathepsin B activity. Moreover, HpGGT was necessary for efficient internalization of the bacteria into gastric cells. This important role of HpGGT in internalization together with the ability to inhibit autophagy posits HpGGT as a key virulence factor in the development of gastric cancer.

Increased Production of Matrix Metalloproteinases in Helicobacter pylori Infection that Stimulates Gastric Cancer Stem Cells

2020 ◽  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Helicobacter Pylori ◽  
Cancer Stem Cells ◽  
Histopathological Examination ◽  
Physiological Saline ◽  
Rrna Gene ◽  
Peptic Ulcers ◽  
Gastric Cancer Stem Cells ◽  
H Pylori

Background and aim: Helicobacter pylori (H. pylori) is an incriminated pathogen causing diseases in both animals and humans and considered a zoonotic pathogen. H. pylori infection is considered a cause of gastric cancer, which rests a significant health care challenge. This study analyzes the expression pattern of matrix metalloprotein 2 (MMP-2) in patients with Helicobacter pylori-associated gastritis and the effect of H. pylori on gastric cancer stem cells, as well as study the role of helicon bacteriosis in dog in transmission of H. pylori infection to human. Materials and methods: Fifty-five of each sample (gastric biopsy, blood and stool) were collected from patients suffering from dyspepsia, chronic vomiting and perforated peptic ulcers and also from apparent healthy dogs. The investigation detected H. pylori by serological and histopathological examination. Biopsies were stored in physiological saline for identification of H. pylori by conventional time PCR. MMP-2 and Gastric cancer stem cells were then identified by immunohistochemistry. Results: Serological identification for H. pylori Antigen and Antibodies revealed (63% human, 50% dogs) and (87% human, 90% dogs) respectively were positive. Genotyping of H. pylori based on 16S rRNA gene showed 54.5% of human and 35% of dogs were positive. Immunohistochemistry revealed strong expression of CD44 in H. pylori- associated gastric cancer cases, MMP-2 expression was observed in all neoplastic lesions associated with H. pylori infection. Conclusion: H. pylori infection affects gastric mucosa and induces changes in gastric stem cells altering their differentiation and increased expression of MMP’s and CD44with a resultant potentiation of oncogenic alteration. In addition the up-regulation of both markers could be an instrumental to interpret the origination of gastric cancer.

Synthesis, Molecular Modelling and Antibacterial Activity Against Helicobacter pylori of Novel Diflunisal Derivatives as Urease Enzyme Inhibitors

2019 ◽  
Vol 16 (4) ◽  
pp. 392-400 ◽  
Author(s):  
Göknil Pelin Coşkun ◽  
Teodora Djikic ◽  
Sadık Kalaycı ◽  
Kemal Yelekçi ◽  
Fikrettin Şahin ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibacterial Activity ◽  
Enzyme Inhibitors ◽  
Binding Modes ◽  
Bacterial Strains ◽  
Urease Enzyme ◽  
H Pylori ◽  
Ulcer Treatment ◽  
Main Factor

Background:The main factor for the prolongation of the ulcer treatment in the gastrointestinal system would be Helicobacter pylori infection, which can possibly lead to gastrointestinal cancer. Triple therapy is the treatment of choice by today's standards. However, observed resistance among the bacterial strains can make the situation even worse. Therefore, there is a need to discover new targeted antibacterial therapy in order to make success in the eradication of H. pylori infections.Methods:The targeted therapy rule is to identify the related macromolecules that are responsible for the survival of the bacteria. Thus, 2-[(2',4'-difluoro-4-hydroxybiphenyl-3-yl)carbonyl]-N- (substituted)hydrazinocarbothioamide (3-13) and 5-(2',4'-difluoro-4-hydroxybiphenyl-3-yl)-4- (substituted)-2,4-dihydro-3H-1,2,4-triazole-3-thiones (14-17) were synthesized and evaluated for antibacterial activity in vitro against H. pylori.Results:All of the tested compounds showed remarkable antibacterial activity compared to the standard drugs (Ornidazole, Metronidazole, Nitrimidazin and Clarithromycin). Compounds 4 and 13 showed activity as 2µg/ml MIC value.Conclusion:In addition, we have investigated binding modes and energy of the compounds 4 and 13 on urease enzyme active by using the molecular docking tools.

scholarly journals The correlation between lncRNAs and Helicobacter pylori in gastric cancer

2019 ◽  
Vol 77 (9) ◽  
Author(s):  
Narges Dastmalchi ◽  
Seyed Mahdi Banan Khojasteh ◽  
Mirsaed Miri Nargesi ◽  
Reza Safaralizadeh
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Molecular Mechanisms ◽  
Gastrointestinal Diseases ◽  
Mechanisms Of Action ◽  
Molecular Pathways ◽  
Gastric Diseases ◽  
Non Coding Rnas ◽  
H Pylori ◽  
The Relationship

ABSTRACT Helicobacter pylori infection performs a key role in gastric tumorigenesis. Long non-coding RNAs (lncRNAs) have demonstrated a great potential to be regarded as effective malignancy biomarkers for various gastrointestinal diseases including gastric cancer (GC). The present review highlights the relationship between lncRNAs and H. pylori in GC. Several studies have examined not only the involvement of lncRNAs in H. pylori-associated GC progression but also their molecular mechanisms of action. Among the pertinent studies, some have addressed the effects of H. pylori infection on modulatory networks of lncRNAs, while others have evaluated the effects of changes in the expression level of lncRNAs in H. pylori-associated gastric diseases, especially GC. The relationship between lncRNAs and H. pylori was found to be modulated by various molecular pathways.

scholarly journals Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development

2021 ◽  
Vol 22 (9) ◽  
pp. 4823
Author(s):  
María Fernanda González ◽  
Paula Díaz ◽  
Alejandra Sandoval-Bórquez ◽  
Daniela Herrera ◽  
Andrew F. G. Quest
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Extracellular Vesicles ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Gastric Epithelium ◽  
Infected Cells ◽  
H Pylori

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

scholarly journals Role of TNF-α-Inducing Protein Secreted by Helicobacter pylori as a Tumor Promoter in Gastric Cancer and Emerging Preventive Strategies

Toxins ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 181
Author(s):  
Masami Suganuma ◽  
Tatsuro Watanabe ◽  
Eisaburo Sueoka ◽  
In Kyoung Lim ◽  
Hirota Fujiki
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cell Surface Receptor ◽  
Tumor Promoter ◽  
Cancer Development ◽  
Human Gastric Cancer ◽  
Tnf Α ◽  
Surface Receptor ◽  
H Pylori ◽  
Factor Α

The tumor necrosis factor-α (TNF-α)-inducing protein (tipα) gene family, comprising Helicobacter pylori membrane protein 1 (hp-mp1) and tipα, has been identified as a tumor promoter, contributing to H. pylori carcinogenicity. Tipα is a unique H. pylori protein with no similarity to other pathogenicity factors, CagA, VacA, and urease. American H. pylori strains cause human gastric cancer, whereas African strains cause gastritis. The presence of Tipα in American and Euro-Asian strains suggests its involvement in human gastric cancer development. Tipα secreted from H. pylori stimulates gastric cancer development by inducing TNF-α, an endogenous tumor promoter, through its interaction with nucleolin, a Tipα receptor. This review covers the following topics: tumor-promoting activity of the Tipα family members HP-MP1 and Tipα, the mechanism underlying this activity of Tipα via binding to the cell-surface receptor, nucleolin, the crystal structure of rdel-Tipα and N-terminal truncated rTipα, inhibition of Tipα-associated gastric carcinogenesis by tumor suppressor B-cell translocation gene 2 (BTG2/TIS21), and new strategies to prevent and treat gastric cancer. Thus, Tipα contributes to the carcinogenicity of H. pylori by a mechanism that differs from those of CagA and VacA.

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