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1.
Helicobacter pylori Biofilm and New Strategies to Combat it.
Moghadam, MT, Chegini, Z, Khoshbayan, A, Farahani, I, Shariati, A
Current molecular medicine. 2021;(7):549-561
Abstract
Helicobacter pylori, the most frequent pathogen worldwide that colonizes around 50% of the world's population, causes important diseases such as gastric adenocarcinoma, chronic gastritis, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In recent years, various studies have reported that H. pylori biofilm may be one of the critical barriers to the eradication of this bacterial infection. Biofilms inhibit the penetration of antibiotics, increase the expression of efflux pumps and mutations, multiple therapeutic failures, and chronic infections. Nanoparticles and natural products can demolish H. pylori biofilm by destroying the outer layers and inhibiting the initial binding of bacteria. Also, the use of combination therapies destroying extracellular polymeric substances decreases coccoid forms of bacteria and degrading polysaccharides in the outer matrix that lead to an increase in the permeability and performance of antibiotics. Different probiotics, antimicrobial peptides, chemical substances, and polysaccharides by inhibiting adhesion and colonization of H. pylori can prevent biofilm formation by this bacterium. Of note, many of the above are applicable to acidic pH and can be used to treat gastritis. Therefore, H. pylori biofilm may be one of the major causes of failure to eradication of infections caused by this bacterium, and antibiotics are not capable of destroying the biofilm. Thus, it is necessary to use new strategies to prevent recurrent and chronic infections by inhibiting biofilm formation.
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2.
Review: Helicobacter pylori infection in children.
Seo, JH, Bortolin, K, Jones, NL
Helicobacter. 2020;:e12742
Abstract
Helicobacter pylori infection in children and adolescents differs in comparison to adults with respect to epidemiology, host responses, and disease manifestations. Furthermore, treatment options are limited in this population and antibiotic resistance rates continue to increase. Therefore, ongoing research is vital to understand disease pathogenesis and provide optimal management of children with infection. This review summarizes relevant publications from April 2019 to March 2020. Similar to adults, recent studies show a decreasing prevalence of infection in the pediatric population. Studies of pathogenesis investigated serum immune responses and the potential inverse association of infection and allergy. Several studies investigated the effect of H pylori and related inflammation on the gut microbiome. The recommendation of endoscopy-based testing to identify the cause of symptoms and not just H pylori, reserving noninvasive UBT or stool antigen tests for post-eradication follow-up, was supported by the current literature.
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3.
Efficacy of Vonoprazan for Helicobacter pylori Eradication.
Kiyotoki, S, Nishikawa, J, Sakaida, I
Internal medicine (Tokyo, Japan). 2020;(2):153-161
Abstract
Helicobacter pylori can infect the gastric mucosa and cause chronic inflammation, resulting in various diseases, including gastric cancer. Eradication of H. pylori in all infected subjects is recommended; however, the number of H. pylori strains with antibiotic resistance has increased, and the eradication rate has decreased. Vonoprazan, a potassium-competitive acid blocker, produces a stronger acid-inhibitory effect than proton pump inhibitors (PPIs). The H. pylori eradication rate with vonoprazan was found to be higher than that with PPIs. The H. pylori eradication rate with vonoprazan-based triple therapy (vonoprazan, amoxicillin, and clarithromycin) was approximately 90% and had an incidence of adverse events similar to that of PPIs. We review the current situation of H. pylori eradication in Japan, the first country in which vonoprazan was made available.
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4.
ATP Analogues for Structural Investigations: Case Studies of a DnaB Helicase and an ABC Transporter.
Lacabanne, D, Wiegand, T, Wili, N, Kozlova, MI, Cadalbert, R, Klose, D, Mulkidjanian, AY, Meier, BH, Böckmann, A
Molecules (Basel, Switzerland). 2020;(22)
Abstract
Nucleoside triphosphates (NTPs) are used as chemical energy source in a variety of cell systems. Structural snapshots along the NTP hydrolysis reaction coordinate are typically obtained by adding stable, nonhydrolyzable adenosine triphosphate (ATP) -analogues to the proteins, with the goal to arrest a state that mimics as closely as possible a physiologically relevant state, e.g., the pre-hydrolytic, transition and post-hydrolytic states. We here present the lessons learned on two distinct ATPases on the best use and unexpected pitfalls observed for different analogues. The proteins investigated are the bacterial DnaB helicase from Helicobacter pylori and the multidrug ATP binding cassette (ABC) transporter BmrA from Bacillus subtilis, both belonging to the same division of P-loop fold NTPases. We review the magnetic-resonance strategies which can be of use to probe the binding of the ATP-mimics, and present carbon-13, phosphorus-31, and vanadium-51 solid-state nuclear magnetic resonance (NMR) spectra of the proteins or the bound molecules to unravel conformational and dynamic changes upon binding of the ATP-mimics. Electron paramagnetic resonance (EPR), and in particular W-band electron-electron double resonance (ELDOR)-detected NMR, is of complementary use to assess binding of vanadate. We discuss which analogues best mimic the different hydrolysis states for the DnaB helicase and the ABC transporter BmrA. These might be relevant also to structural and functional studies of other NTPases.
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5.
Carbohydrate-Dependent and Antimicrobial Peptide Defence Mechanisms Against Helicobacter pylori Infections.
Padra, M, Benktander, J, Robinson, K, Lindén, SK
Current topics in microbiology and immunology. 2019;:179-207
Abstract
The human stomach is a harsh and fluctuating environment for bacteria with hazards such as gastric acid and flow through of gastric contents into the intestine. H. pylori gains admission to a stable niche with nutrient access from exudates when attached to the epithelial cells under the mucus layer, whereof adherence to glycolipids and other factors provides stable and intimate attachment. To reach this niche, H. pylori must overcome mucosal defence mechanisms including the continuously secreted mucus layer, which provides several layers of defence: (1) mucins in the mucus layer can bind H. pylori and transport it away from the gastric niche with the gastric emptying, (2) mucins can inhibit H. pylori growth, both via glycans that can have antibiotic like function and via an aggregation-dependent mechanism, (3) antimicrobial peptides (AMPs) have antimicrobial activity and are retained in a strategic position in the mucus layer and (4) underneath the mucus layer, the membrane-bound mucins provide a second barrier, and can function as releasable decoys. Many of these functions are dependent on H. pylori interactions with host glycan structures, and both the host glycosylation and concentration of antimicrobial peptides change with infection and inflammation, making these interactions dynamic. Here, we review our current understanding of mucin glycan and antimicrobial peptide-dependent host defence mechanisms against H. pylori infection.
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6.
Review: Helicobacter pylori in pediatrics.
Mišak, Z, Hojsak, I, Homan, M
Helicobacter. 2019;:e12639
Abstract
Despite a decrease in the prevalence of Helicobacter pylori infection, it still poses a significant health burden worldwide. This review summarizes important pediatric studies on H pylori published from April 2018 to March 2019. Epidemiologic studies have reported different prevalences in different parts of the world and have mainly confirmed traditional risk factors. Several studies on pathophysiology attempted to identify risk markers in childhood for gastric cancer development later in life. One of the most interesting studies evaluated the relationship between eosinophilic esophagitis and H pylori infection; however, an inverse relationship was not confirmed. The high resistance of H pylori and, consequently, low eradication rates, is still a major concern and susceptibility testing before treatment has again been highlighted. Potassium-competitive acid blockers are promising new acid-suppressant drugs but their role in H pylori eradication schemes is still to be determined.
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7.
Review: Helicobacter pylori and extragastric diseases.
Franceschi, F, Covino, M, Roubaud Baudron, C
Helicobacter. 2019;:e12636
Abstract
In the last year, many studies have demonstrated a potential role of Helicobacter pylori in the pathogenic mechanisms of different extragastric diseases. While the role of H pylori in idiopathic thrombocytopenic purpura, idiopathic iron deficiency anemia, and vitamin B12 deficiency has already been demonstrated, there is growing evidence of other related conditions, especially cardiovascular, metabolic, and neurologic disorders, including neurodegenerative diseases. A summary of the results of the most relevant studies published over the last year on this attractive topic is presented in this review.
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8.
Probiotic therapy in Helicobacter pylori infection: a potential strategy against a serious pathogen?
Qureshi, N, Li, P, Gu, Q
Applied microbiology and biotechnology. 2019;(4):1573-1588
Abstract
Helicobacter pylori is a highly prevalent human pathogen responsible for chronic inflammation of the gastric tissues, gastroduodenal ulcers, and cancer. The treatment includes a pair of antibiotics with a proton pump inhibitor PPI. Despite the presence of different treatments, the infection rate is still increasing both in developed and developing states. The challenge of treatment failure is greatly due to the resistance of H. pylori to antibiotics and its side effects. Probiotics potential to cure H. pylori infection is well-documented. Probiotics combined with conventional treatment regime appear to have great potential in eradicating H. pylori infection, therefore, provide an excellent alternative approach to manage H. pylori load and its threatening disease outcome. Notably, anti-H. pylori activity of probiotics is strain specific,therefore establishing standard guidelines regarding the dose and formulation of individual strain is inevitable. This review is focused on probiotic's antagonism against H. pylori summarizing their three main potential aspects: their efficiency (i) as an alternative to H. pylori eradication treatment, (ii) as an adjunct to H. pylori eradication treatment and (iii) as a vaccine delivery vehicle.
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9.
Gastric cancer: epidemiology, biology, and prevention: a mini review.
Lyons, K, Le, LC, Pham, YT, Borron, C, Park, JY, Tran, CTD, Tran, TV, Tran, HT, Vu, KT, Do, CD, et al
European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP). 2019;(5):397-412
Abstract
Gastric cancer is one of the most common causes of cancer-related mortality worldwide. The objective of this article is to review the epidemiology and biology of gastric cancer risk. This literature review explores the biological, clinical, and environmental factors that influence the rates of this disease and discuss the different intervention methods that may not only increase the awareness of gastric cancer but also increase screening in efforts to reduce the risk of gastric cancer. Helicobacter pylori infection is the primary risk factor for gastric cancer. Additional risk factors include geographical location, age, sex, smoking, socioeconomic status, dietary intake, and genetics. Primary and secondary prevention strategies such as dietary modifications and screenings are important measures for reducing the risk of gastric cancer. Interventions, such as H. pylori eradication through chemoprevention trials, have shown some potential as a preventative strategy. Although knowledge about gastric cancer risk has greatly increased, future research is warranted on the differentiation of gastric cancer epidemiology by subsite and exploring the interactions between H. pylori infection, genetics, and environmental factors. Better understanding of these relationships can help researchers determine the most effective intervention strategies for reducing the risk of this disease.
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10.
Gastric Parietal Cell Physiology and Helicobacter pylori-Induced Disease.
Yao, X, Smolka, AJ
Gastroenterology. 2019;(8):2158-2173
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Abstract
Acidification of the gastric lumen poses a barrier to transit of potentially pathogenic bacteria and enables activation of pepsin to complement nutrient proteolysis initiated by salivary proteases. Histamine-induced activation of the PKA signaling pathway in gastric corpus parietal cells causes insertion of proton pumps into their apical plasma membranes. Parietal cell secretion and homeostasis are regulated by signaling pathways that control cytoskeletal changes required for apical membrane remodeling and organelle and proton pump activities. Helicobacter pylori colonization of human gastric mucosa affects gastric epithelial cell plasticity and homeostasis, promoting epithelial progression to neoplasia. By intervening in proton pump expression, H pylori regulates the abundance and diversity of microbiota that populate the intestinal lumen. We review stimulation-secretion coupling and renewal mechanisms in parietal cells and the mechanisms by which H pylori toxins and effectors alter cell secretory pathways (constitutive and regulated) and organelles to establish and maintain their inter- and intracellular niches. Studies of bacterial toxins and their effector proteins have provided insights into parietal cell physiology and the mechanisms by which pathogens gain control of cell activities, increasing our understanding of gastrointestinal physiology, microbial infectious disease, and immunology.