Materiały źródłowe

• #1

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6138426/

  Helicobacter pylori pathogenesis and disease outcomes are mediated by a complex interplay between bacterial virulence factors, host, and environmental factors. After H. pylori enters the host stomach, four steps are critical for bacteria to establish successful colonization, persistent infection, and disease pathogenesis: (1) Survival in the acidic stomach; (2) movement toward epithelium cells by flagella-mediated motility; (3) attachment to host cells by adhesins/receptors interaction; (4) causing tissue damage by toxin release. […] Recently, the development of large-scale screening methods, including proteomic, and transcriptomic tools, has been used to determine the complex gene regulatory networks in H. pylori. […] After entering the host stomach, H. pylori utilizes its urease activity to neutralize the hostile acidic condition at the beginning of infection. Flagella-mediated motility is then required for H. pylori to move toward host gastric epithelium cells, followed by specific interactions between bacterial adhesins with host cell receptors, which thus leads to successful colonization and persistent infection. Finally, H. pylori releases several effector proteins/toxins, including cytotoxin-associated gene A (CagA), and vacuolating cytotoxin A (VacA), causing host tissue damage.

• #2 Pathogenesis of Helicobacter pylori Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1539101/

  Helicobacter pylori is the first formally recognized bacterial carcinogen and is one of the most successful human pathogens, as over half of the world’s population is colonized with this gram-negative bacterium. H. pylori infection represents a key factor in the etiology of various gastrointestinal diseases, ranging from chronic active gastritis without clinical symptoms to peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Disease outcome is the result of the complex interplay between the host and the bacterium. Host immune gene polymorphisms and gastric acid secretion largely determine the bacterium’s ability to colonize a specific gastric niche. Bacterial virulence factors such as the cytotoxin-associated gene pathogenicity island-encoded protein CagA and the vacuolating cytotoxin VacA aid in this colonization of the gastric mucosa and subsequently seem to modulate the host’s immune system. This review focuses on the microbiological, clinical, immunological, and biochemical aspects of the pathogenesis of H. pylori.

• #2

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6138426/

  In summary, four steps are critical for H. pylori colonization and pathogenesis: (1) Survival under acidic stomach conditions; (2) movement toward epithelium cells through flagella-mediated motility; (3) attaching to host receptors by adhesins; (4) causing tissue damage by toxin release. […] H. pylori has developed an acid acclimation mechanism that promotes adjustment of periplasmic pH in the harsh acidic environment of the stomach by regulating urease activity. […] Urease is also found on the H. pylori surface due to the lysis of some organisms. […] H. pylori moves through the gastric mucosa epithelium layer to the basal layer where the pH value is close to 7.0 by the action of 47 polar sheathed flagella. […] H. pylori flagella are mainly composed of the basal body, hook, and flagellar filament.

• #3 Helicobacter pylori – Wikipedia

  https://en.wikipedia.org/wiki/Helicobacter_pylori

  H. pylori has from two to seven flagella at the same polar location which gives it a high motility. The flagellar filaments are about 3 m long, and composed of two copolymerized flagellins, FlaA and FlaB, coded by the genes flaA, and flaB. The flagella are sheathed in a continuation of the bacterial outer membrane which gives protection against the gastric acidity. The sheath is also the location of the origin of the outer membrane vesicles that gives protection to the bacterium from bacteriophages. Flagella motility is provided by the proton motive force provided by urease-driven hydrolysis allowing chemotactic movements towards the less acidic pH gradient in the mucosa. […] In addition to using chemotaxis to avoid areas of high acidity (low pH), H. pylori also produces large amounts of urease, an enzyme which breaks down the urea present in the stomach to produce ammonia and bicarbonate, which are released into the bacterial cytosol and the surrounding environment, creating a neutral area. The decreased acidity (higher pH) changes the mucus layer from a gel-like state to a more viscous state that makes it easier for the flagella to move the bacteria through the mucosa and attach to the gastric epithelial cells. Urease is the bacterium’s most abundant protein, accounting for 10-15% of the bacterium’s total protein content. Its expression is not only required for establishing initial colonization in the breakdown of urea to carbonic acid and ammonia, but is also essential for maintaining chronic infection. Ammonia reduces stomach acidity, allowing the bacteria to become locally established.

• #3

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6138426/

  When H. pylori colonizes on the mucosal layer lining the gastric epithelium, the interaction of bacterial adhesins with cellular receptors protects the bacteria from displacement from the stomach by forces such as those generated by peristalsis and gastric emptying, and then bacteria get metabolic substrates and nutrients to improve growth through releasing toxins to damage the host cells. […] Cytotoxin-associated gene A protein can be further divided into the Western-type CagA and East Asian-type CagA, by the repeat sequence Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs at the N-terminus of CagA. […] Vacuolating cytotoxin A is predicted to encode a protoxin with a mass of about 140 kDa, but the secreted VacA toxin is composed of the p33 and p55 domains that form an oligomeric structure.

• #4 Understanding the survival mechanism of Helicobacter pylori in the stomach | Malvern Panalytical

  https://www.malvernpanalytical.com/en/learn/knowledge-center/insights/understanding-the-survival-mechanism-of-helicobacter-pylori-in-the-stomach

  It is estimated that the Gram-negative bacterium Helicobacter pylori is present in the stomachs of over half the worlds population. H. pylori infection can lead to peptic ulceration and it is the highest risk factor for gastric cancer. The key to H. pylori’s successful pathogenicity lies in its ability to colonize the stomach. […] One unique adaptation of H. pylori is its ability to counteract gastric acid by producing ammonia from urea, using bacterial urease. Another survival mechanism of H. pylori is the use of its adhesion protein BabA to attach to Lewisb antigens, which are naturally expressed sugars on healthy gastric epithelium. Since the bacteria are able to directly attach to epithelial cells, they are able to avoid being cleared from the stomach, and colonization is maintained.

• #4 Helicobacter pylori – Wikipedia

  https://en.wikipedia.org/wiki/Helicobacter_pylori

  H. pylori must make attachment with the epithelial cells to prevent its being swept away with the constant movement and renewal of the mucus. To give them this adhesion, bacterial outer membrane proteins as virulence factors called adhesins are produced. BabA (blood group antigen binding adhesin) is most important during initial colonization, and SabA (sialic acid binding adhesin) is important in persistence. BabA attaches to glycans and mucins in the epithelium. Adherence via BabA is acid sensitive and can be fully reversed by a decreased pH. It has been proposed that BabA’s acid responsiveness enables adherence while also allowing an effective escape from an unfavorable environment such as a low pH that is harmful to the organism. SabA binds to increased levels of sialyl-Lewis X antigen expressed on gastric mucosa.

• #5 Helicobacter pylori – Wikipedia

  https://en.wikipedia.org/wiki/Helicobacter_pylori

  CagA (cytotoxin-associated antigen A) is a major virulence factor for H. pylori, an oncoprotein that is encoded by the cagA gene. Bacterial strains with the cagA gene are associated with the ability to cause ulcers, MALT lymphomas, and gastric cancer. The cagA gene codes for a relatively long (1186-amino acid) protein. The cag pathogenicity island (PAI) has about 30 genes, part of which code for a complex type IV secretion system (T4SS or TFSS). The virulence of H. pylori may be increased by genes of the cag pathogenicity island; about 50-70% of H. pylori strains in Western countries carry it. Western people infected with strains carrying the cag PAI have a stronger inflammatory response in the stomach and are at a greater risk of developing peptic ulcers or stomach cancer than those infected with strains lacking the island. Following attachment of H. pylori to stomach epithelial cells, the type IV secretion system expressed by the cag PAI „injects” the inflammation-inducing agent, peptidoglycan, from their own cell walls into the epithelial cells. The injected peptidoglycan is recognized by the cytoplasmic pattern recognition receptor (immune sensor) Nod1, which then stimulates expression of cytokines that promote inflammation.

• #6 Helicobacter pylori – Wikipedia

  https://en.wikipedia.org/wiki/Helicobacter_pylori

  The type-IV secretion apparatus also injects the cag PAI-encoded protein CagA into the stomach’s epithelial cells, where it disrupts the cytoskeleton, adherence to adjacent cells, intracellular signaling, cell polarity, and other cellular activities. Once inside the cell, the CagA protein is phosphorylated on tyrosine residues by a host cell membrane-associated tyrosine kinase (TK). CagA then allosterically activates protein tyrosine phosphatase/protooncogene Shp2. These proteins are directly toxic to cells lining the stomach and signal strongly to the immune system that an invasion is under way. As a result of the bacterial presence, neutrophils and macrophages set up residence in the tissue to fight the bacteria assault. Pathogenic strains of H. pylori have been shown to activate the epidermal growth factor receptor (EGFR), a membrane protein with a TK domain. Activation of the EGFR by H. pylori is associated with altered signal transduction and gene expression in host epithelial cells that may contribute to pathogenesis.

• #7 Helicobacter pylori: A Contemporary Perspective on Pathogenesis, Diagnosis and Treatment Strategies

  https://www.mdpi.com/2076-2607/12/1/222

  The vacuolating toxin, VacA, is another key virulence factor, that exhibits multifaceted effects on the host cells. As the name suggests, VacA disrupts the integrity of the gastric epithelial barrier by forming channels or pores in the cell membrane, leading to increased permeability. Within the host cells, VacA modulates the apoptotic pathways, leading to both pro- and antiapoptotic effects depending on the cell type and environmental conditions. […] The immune response to H. pylori infection is a dynamic interplay between the bacterial factors and the host’s immune system. The pathogenesis of H. pylori infections unfolds through a complex and multifaceted localized gastric inflammatory response. The sustained presence of H. pylori leads to chronic inflammation, causing ongoing tissue damage and remodeling. The gastric epithelial cells undergo changes in turnover, with increased proliferation contributing to mucosal damage and ulcer formation.

• #8 H. Pylori Infection: Symptoms, Causes, and More

  https://www.healthline.com/health/helicobacter-pylori

• #9 Peptic ulcer disease – Wikipedia

  https://en.wikipedia.org/wiki/Peptic_ulcer_disease

  Helicobacter pylori is one of the major causative factors of peptic ulcer disease. […] It secretes urease to create an alkaline environment, which is suitable for its survival. […] It expresses blood group antigen-binding adhesin (BabA) and outer inflammatory protein adhesin (OipA), which enables it to attach to the gastric epithelium. […] The bacterium also expresses virulence factors such as CagA and PicB, which cause stomach mucosal inflammation. […] The VacA gene encodes for vacuolating cytotoxin, but its mechanism of causing peptic ulcers is unclear. […] Such stomach mucosal inflammation can be associated with hyperchlorhydria (increased stomach acid secretion) or hypochlorhydria (reduced stomach acid secretion). […] Inflammatory cytokines inhibit the parietal cell acid secretion.

• #10 Pathogenesis and clinical management of Helicobacter pylori gastric infection

  https://www.wjgnet.com/1007-9327/full/v25/i37/5578.htm

  Other various virulence factors have been related to an increased H. pylori capacity to impair gastric homeostasis. Among them, VacA is a determinant protein for H. pylori pathogenicity, and its gene is present in almost all bacterial strains. VacA promotes the formation of acidic vacuoles in the cytoplasm of gastric epithelial cells. Consequently, the integrity of mitochondria, cytoplasmic membrane, and endomembranous structures is destabilized, leading cells to collapse. Moreover, this protein might also promote the activation and suppression of the immune response, inducing immune tolerance and persistent H. pylori infection through its activities on T-cells and antigen-presenting cells. […] Complex host immune responses, embracing innate and adaptive mechanisms, are induced by H. pylori infection. Given the initial contact with the pathogen, various H. pylori antigens such as lipoteichoic acid, lipoproteins, lipopolysaccharide, HSP-60, NapA, DNA, and RNA bind to gastric cell receptors, including toll-like receptor (TLR) 1, TLR2, TLR4, TLR5, TLR6, and TLR10 located on epithelial cell membranes, and TLR9, found in intracellular vesicles. Such interaction promotes, among other signaling pathways, NF-B and c-jun N-terminal kinase activation, followed by proinflammatory cytokine release.

• #11 Helicobacter pylori – Wikipedia

  https://en.wikipedia.org/wiki/Helicobacter_pylori

  The outer membrane contains cholesterol glucoside, a sterol glucoside that H. pylori glycosylates from the cholesterol in the gastric gland cells, and inserts it into its outer membrane. This cholesterol glucoside is important for membrane stability, morphology and immune evasion, and is rarely found in other bacteria. The enzyme responsible for this is cholesteryl-glucosyltransferase (CgT or Cgt), encoded by the HP0421 gene. A major effect of the depletion of host cholesterol by Cgt is to disrupt cholesterol-rich lipid rafts in the epithelial cells. Lipid rafts are involved in cell signalling and their disruption causes a reduction in the immune inflammatory response, particularly by reducing interferon gamma. […] Colonization induces an intense anti-inflammatory response as a first-line immune system defence. Phagocytic leukocytes and monocytes infiltrate the site of infection, and antibodies are produced. H. pylori is able to adhere to the surface of the phagocytes and impede their action. This is responded to by the phagocyte in the generation and release of oxygen metabolites into the surrounding space. H. pylori can survive this response by the activity of catalase at its attachment to the phagocytic cell surface. Catalase decomposes hydrogen peroxide into water and oxygen, protecting the bacteria from toxicity.

• #12 Pathogenesis of Helicobacter pylori Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1539101/

  H. pylori-induced ulcer disease, gastric cancer, and lymphoma are all complications of this chronic inflammation; ulcer disease and gastric cancer in particular occur in those individuals and at those sites with the most severe inflammation. Understanding of these factors is thus crucial for the recognition of the role of H. pylori in the etiology of upper gastrointestinal pathology. […] The primary disorder, which occurs after colonization with H. pylori, is chronic active gastritis. This condition can be observed in all H. pylori-positive subjects. The intragastric distribution and severity of this chronic inflammatory process depend on a variety of factors, such as characteristics of the colonizing strain, host genetics and immune response, diet, and the level of acid production.

• #13 Helicobacter pylori and gastric cancer: mechanisms and new perspectives | Journal of Hematology & Oncology | Full Text

  https://jhoonline.biomedcentral.com/articles/10.1186/s13045-024-01654-2

  The chronic inflammatory response triggered by H. pylori is a significant risk factor for gastric carcinogenesis, involving complex interactions with other carcinogenic processes, such as oxidative stress and aberrant activation of cancer pathways. […] The chronic inflammatory response stimulated by H. pylori is a critical mechanism in gastric carcinogenesis. […] Deregulation of cell apoptosis is a key event in H. pylori-induced gastric carcinogenesis, and H. pylori is capable of manipulating apoptosis in gastric epithelial cells to favor tumor survival and expansion. […] The inhibition of apoptosis is a critical molecular mechanism in carcinogenesis. […] H. pylori employs additional strategies contributing to gastric cancer development, including interference with cell cycle progression and autophagy. […] The autophagic process and its alterations significantly affect the development of gastric cancer. […] The extensive review of the mechanisms by which H. pylori contributes to gastric cancer underscores the complexity involving the synergy of multiple pathways and multifactorial nature of this bacterium’s role in carcinogenesis.

• #14 Helicobacter pylori (H. pylori) infection – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/h-pylori/symptoms-causes/syc-20356171

  Helicobacter pylori (H. pylori) infection occurs when Helicobacter pylori (H. pylori) bacteria infect your stomach. This usually happens during childhood. A common cause of stomach ulcers (peptic ulcers), H. pylori infection may be present in more than half the people in the world. […] H. pylori infection occurs when H. pylori bacteria infect your stomach. H. pylori bacteria are usually passed from person to person through direct contact with saliva, vomit or stool. H. pylori may also be spread through contaminated food or water. The exact way H. pylori bacteria causes gastritis or a peptic ulcer in some people is still unknown. […] H. pylori can damage the protective lining of the stomach and small intestine. This can allow stomach acid to create an open sore (ulcer). About 10% of people with H. pylori will develop an ulcer. […] H. pylori infection can affect the stomach, causing irritation and swelling (gastritis). […] H. pylori infection is a strong risk factor for certain types of stomach cancer.

• #15 Helicobacter Pylori Infection: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/176938-overview

  Helicobacter pylori (see the image below) is a ubiquitous organism that is present in about 50% of the global population. Chronic infection with H pylori causes atrophic and even metaplastic changes in the stomach, and it has a known association with peptic ulcer disease. […] The most common route of H pylori infection is either oral-to-oral or fecal-to-oral contact. […] In a susceptible host, H pylori results in chronic active gastritis that may lead, in turn, to duodenal and gastric ulcer disease, gastric cancer, and MALTomas. H pylori infection causes chronic active gastritis, which is characterized by a striking infiltration of the gastric epithelium and the underlying lamina propria by neutrophils, T and B lymphocytes, macrophages, and mast cells. […] The release of host cytokines after direct contact of H pylori with the epithelial cells of the gastric lining could recall the inflammatory cells in the infected area.

• #16 Helicobacter pylori Infection – Gastrointestinal Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gastrointestinal-disorders/gastritis-and-peptic-ulcer-disease/helicobacter-pylori-infection

  Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. […] H. pylori is a spiral-shaped, gram-negative organism that has adapted to thrive in acid. […] Effects of H. pylori infection vary depending on the location within the stomach. […] Antral-predominant infection results in increased gastrin production, probably via local impairment of somatostatin release. Resultant hypersecretion of acid predisposes to prepyloric and duodenal ulcer. […] Body-predominant infection leads to gastric atrophy and decreased acid production, possibly via increased local production of interleukin-1 beta. Patients with body-predominant infection are predisposed to gastric ulcer and gastric adenocarcinoma.

• #17 Helicobacter pylori Infection – Gastrointestinal Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gastrointestinal-disorders/gastritis-and-peptic-ulcer-disease/helicobacter-pylori-infection

  Ammonia produced by H. pylori enables the organism to survive in the acidic environment of the stomach and may erode the mucus barrier. […] Cytotoxins and mucolytic enzymes (eg, bacterial protease, lipase) produced by H. pylori may play a role in mucosal damage and subsequent ulcerogenesis. […] Infected people are more likely to develop stomach cancer. […] H. pylori is a group 1 carcinogen (carcinogenic to humans). […] H. pylori infection is associated with intestinal-type adenocarcinoma of the gastric body and antrum but not cancer of the gastric cardia. Other associated cancers include gastric lymphoma and mucosa-associated lymphoid tissue (MALT) lymphoma, a monoclonally restricted B-cell tumor. […] H. pylori eradication requires multidrug therapy, typically antibiotics plus acid suppressants.

• #18 Helicobacter pylori (H. pylori) and Cancer – NCI

  https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/h-pylori-fact-sheet

  Helicobacter pylori (H. pylori) is a spiral-shaped bacterium that grows in the mucus layer that coats the inside of the human stomach. Although many bacteria cannot survive the stomachs acid environment, H. pylori is able to neutralize the acidity of its local environment in the stomach, though not the stomach as a whole. This local neutralization helps the bacterium survive. […] H. pylori also interferes with local immune responses, making them ineffective in eliminating this bacterium. […] Yes. Although H. pylori infection does not itself cause illness, chronic infection causes long-lasting inflammation in the stomach (called non-atrophic gastritis) in most people. This inflammation can lead to several possible conditions, including atrophic gastritis (thinning of the stomach lining caused by long-term inflammation) and certain types of stomach (gastric) cancer, particularly gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma, which is a rare type of non-Hodgkin lymphoma. […] Because of its role in causing stomach cancer, in 1994 H. pylori was classified as a human carcinogen, or cancer-causing agent, by the World Health Organizations International Agency for Research on Cancer.

• #19 H. pylori and stomach cancer: Connection explained

  https://www.medicalnewstoday.com/articles/h-pylori-and-stomach-cancer

  Helicobacter pylori (H. pylori) are bacteria that live in the stomach of about two-thirds of the global population. Strong evidence suggests that it can cause cancer. […] H. pylori is common globally with regional variances. Left untreated, it can lead to several potential health issues, including stomach cancer. […] Both the International Agency for Research on Cancer and the World Health Organization (WHO) classified H. pylori as a type I carcinogen in 1994. A type I carcinogen means that enough scientific evidence supports a claim that the substance or thing in this case, H. pylori causes cancer. […] The exact mechanism of how H. pylori causes stomach cancer is not fully understood, but scientists think that several factors likely contribute to its development. […] According to a 2021 review article, H. pylori can increase the risk of gastric (stomach) cancer.

• #20 Helicobacter pylori – Wikipedia

  https://en.wikipedia.org/wiki/Helicobacter_pylori

  Helicobacter pylori, previously known as Campylobacter pylori, is a gram-negative, flagellated, helical bacterium. Its helical body (from which the genus name Helicobacter derives) is thought to have evolved to penetrate the mucous lining of the stomach, helped by its flagella, and thereby establish infection. The bacterium was first identified as the causal agent of gastric ulcers in 1983 by Australian physician-scientists Barry Marshall and Robin Warren. Infection of the stomach with H. pylori does not necessarily cause illness: over half of the global population is infected, but most individuals are asymptomatic. Persistent colonization with more virulent strains can induce a number of gastric and non-gastric disorders. Gastric disorders due to infection begin with gastritis, or inflammation of the stomach lining. When infection is persistent, the prolonged inflammation will become chronic gastritis. Initially, this will be non-atrophic gastritis, but the damage caused to the stomach lining can bring about the development of atrophic gastritis and ulcers within the stomach itself or the duodenum (the nearest part of the intestine). At this stage, the risk of developing gastric cancer is high. However, the development of a duodenal ulcer confers a comparatively lower risk of cancer. Helicobacter pylori are class 1 carcinogenic bacteria, and potential cancers include gastric MALT lymphoma and gastric cancer. Infection with H. pylori is responsible for an estimated 89% of all gastric cancers and is linked to the development of 5.5% of all cases cancers worldwide. H. pylori is the only bacterium known to cause cancer.

• #21 Helicobacter pylori (H. pylori) and Cancer – NCI

  https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/h-pylori-fact-sheet

  Many studies have provided consistent evidence that chronic H. pylori infection causes gastric adenocarcinoma and gastric MALT lymphoma. […] Epidemiologic studies have shown that people who have chronic H. pylori infections have an increased risk of developing non-cardia gastric adenocarcinoma. […] Nearly all patients with gastric MALT lymphoma show signs of H. pylori infection, and the risk of developing this cancer is substantially greater in infected people than in uninfected people. […] The majority of cases of gastric adenocarcinoma and gastric MALT lymphoma are attributed to H. pylori infection. […] Long-term follow-up data from a randomized clinical trial carried out in Shandong, China showed that 2 weeks of treatment with antibiotics to eradicate H. pylori significantly reduced the incidence of gastric cancer by nearly 50% over 22 years of follow-up after treatment.

• #22 H. pylori and stomach cancer: Connection explained

  https://www.medicalnewstoday.com/articles/h-pylori-and-stomach-cancer

  In a 2017 article, experts noted that H. pylori is the most significant risk factor for gastric cancer and accounts for nearly 90% of all stomach cancers. […] H. pylori is present in nearly 90% of all people with stomach cancer. It is the most common cause and risk factor for gastric cancer. […] If left untreated, H. pylori can lead to the development of stomach ulcers and inflammation. It is a known carcinogen and can eventually cause the development of stomach cancer. […] H. pylori is both a cause and risk factor for the development of stomach cancer. It may also increase the risk of colorectal cancer. […] H. pylori does not cause symptoms, but inflammation in the stomach and ulcer development can lead to nausea, pain, and vomiting.

• #23 Helicobacter pylori – Wikipedia

  https://en.wikipedia.org/wiki/Helicobacter_pylori

  The many virulence factors of H. pylori include its flagella, the production of urease, adhesins, serine protease HtrA (high temperature requirement A), and the major exotoxins CagA and VacA. The presence of VacA and CagA are associated with more advanced outcomes. CagA is an oncoprotein associated with the development of gastric cancer. H. pylori infection is associated with epigenetically reduced efficiency of the DNA repair machinery, which favors the accumulation of mutations and genomic instability as well as gastric carcinogenesis. It has been shown that expression of two DNA repair proteins, ERCC1 and PMS2, was severely reduced once H. pylori infection had progressed to cause dyspepsia. Dyspepsia occurs in about 20% of infected individuals. Epigenetically reduced protein expression of DNA repair proteins MLH1, MGMT and MRE11 are also evident. Reduced DNA repair in the presence of increased DNA damage increases carcinogenic mutations and is likely a significant cause of gastric carcinogenesis. These epigenetic alterations are due to H. pylori-induced methylation of CpG sites in promoters of genes and H. pylori-induced altered expression of multiple microRNAs.

• #24 Helicobacter pylori – Wikipedia

  https://en.wikipedia.org/wiki/Helicobacter_pylori

  Two related mechanisms by which H. pylori could promote cancer have been proposed. One mechanism involves the enhanced production of free radicals near H. pylori and an increased rate of host cell mutation. The other proposed mechanism has been called a „perigenetic pathway”, and involves enhancement of the transformed host cell phenotype by means of alterations in cell proteins, such as adhesion proteins. H. pylori has been proposed to induce inflammation and locally high levels of tumor necrosis factor (TNF), also known as tumor necrosis factor alpha (TNF), and/or interleukin 6 (IL-6). According to the proposed perigenetic mechanism, inflammation-associated signaling molecules, such as TNF, can alter gastric epithelial cell adhesion and lead to the dispersion and migration of mutated epithelial cells without the need for additional mutations in tumor suppressor genes, such as genes that code for cell adhesion proteins.

• #25 Helicobacter pylori – Wikipedia

  https://en.wikipedia.org/wiki/Helicobacter_pylori

  Chronic inflammation that is a feature of cancer development is characterized by infiltration of neutrophils and macrophages to the gastric epithelium, which favors the accumulation of pro-inflammatory cytokines, reactive oxygen species (ROS) and reactive nitrogen species (RNS) that cause DNA damage. The oxidative DNA damage and levels of oxidative stress can be indicated by a biomarker, 8-oxo-dG. Other damage to DNA includes double-strand breaks.

• #26 Helicobacter pylori and gastric cancer: mechanisms and new perspectives | Journal of Hematology & Oncology | Full Text

  https://jhoonline.biomedcentral.com/articles/10.1186/s13045-024-01654-2

  To further understand the function of H. pylori in gastric carcinogenesis, Correa proposed a model for intestinal gastric cancer in 1992, identifying H. pylori infection as the initiating contributor involved in gastric carcinogenesis. […] The International Agency for Research on Cancer (IARC) classified H. pylori as a Group 1 carcinogen in 1994, emphasizing the urgent need for effective diagnostic and treatment strategies. […] The development of gastric cancer involves the following mechanisms that can activate the downstream signaling pathways, including the cytokine-stimulated transduction (JAK-STAT) signaling, the nuclear factor B (NF-B) pathway, the Wnt/-catenin signaling pathway, the mitogen-activated protein kinase (MAPK) pathway, the Hippo pathway, the PI3K/Akt pathway, and other signaling pathways. […] The molecular interplay between H. pylori and the host involves a sophisticated regulation of molecular mechanisms that contribute to gastric carcinogenesis.

• #27 Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

  https://www.mdpi.com/2073-4409/10/1/27

  H. pylori infection enhances the progression of the epithelial–mesenchymal transition (EMT) that induces the oncogenic alterations within the gastric mucosa, constituting one of the hallmarks of gastric carcinogenesis. […] The severity of H. pylori-related diseases is associated with numerous virulence factors; a particular genotype of the H. pylori strain plays a crucial role. Furthermore, what is of the highest importance is an interplay between the host, gastric microenvironment, as well as bacterial virulence factors. H. pylori virulence factors are not only involved in the induction of inflammatory responses, but they also control and regulate those responses, maintaining chronic inflammation. H. pylori exhibits an expanded complex of mechanisms that alters host cellular responses and signaling pathways.

• #28 Helicobacter pylori and gastric cancer: mechanisms and new perspectives | Journal of Hematology & Oncology | Full Text

  https://jhoonline.biomedcentral.com/articles/10.1186/s13045-024-01654-2

  The transcription factor STAT3 is instrumental in the gastric cancer progression stimulated by H. pylori. […] In conclusion, sustained activation of STAT3 represents a key molecular mechanism by which H. pylori promotes gastric carcinogenesis. […] NF-B is a key nuclear transcription factor in gastric carcinogenesis initiated by H. pylori. […] In conclusion, the NF-B pathway functions as a key effector in the development of H. pylori-mediated gastric cancer. […] Wnt/-catenin signaling pathway is a key regulatory mechanism in H. pylori-related gastric cancer. […] In conclusion, Wnt/-catenin signaling pathway is an important driving factor for the induction of gastric cancer by H. pylori, and this pathway plays a crucial role in various stages of carcinogenesis, including the early initiation and progression of gastric cancer.

• #29 Helicobacter pylori and gastric cancer: mechanisms and new perspectives | Journal of Hematology & Oncology | Full Text

  https://jhoonline.biomedcentral.com/articles/10.1186/s13045-024-01654-2

  Accumulating evidence has revealed that oxidative stress, which is characterized by an elevated level of ROS and reactive nitrogen species (RNS), is involved in the development of gastric cancer. […] In summary, H. pylori-induced oxidative stress sets the stage for the initiation and progression of gastric cancer through multiple mechanisms including DNA damage, genomic instability, the undermining of antioxidant defenses, and metabolic disruptions. […] H. pylori infection causes various types of DNA damage, which is one of the important mechanisms by which this bacterium promotes gastric carcinogenesis. […] In summary, H. pylori induces multiple DNA lesions, triggers genomic instability, and interferes with DNA repair mechanisms, creating an environment conducive to gastric cancer.

• #30 Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori | Nature Reviews Microbiology

  https://www.nature.com/articles/nrmicro3016

  Helicobacter pylori persistently colonizes the gastric mucosa of humans, infecting approximately 50% of the population worldwide. The prevalence of H. pylori is decreasing in most parts of the developed world owing to improved sanitation, reduced transmission and the more frequent use of antibiotics in childhood. […] Initial colonization of the hostile environment of the gastric mucosa by H. pylori requires specific adaptations, including flagellar motility, production of urease, chemotaxis and helical cell shape. […] To establish persistent infection, H. pylori has evolved to avoid recognition by pattern recognition receptors of the innate immune system and to preferentially activate receptors coupled to anti-inflammatory signalling pathways. The pathogen-associated molecular patterns of this bacterium are substantially less biologically active than those of related Gram-negative enteropathogens.

• #31 Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori | Nature Reviews Microbiology

  https://www.nature.com/articles/nrmicro3016

  Another H. pylori persistence strategy involves the prevention and manipulation of T cell-mediated adaptive immunity. Specific virulence factors are produced by all strains of H. pylori to block T cell activation, proliferation and effector functions, and to preferentially induce regulatory T cell responses rather than effector T cell responses. Asymptomatic carriers are more likely to preferentially generate TReg responses and harbour denser H. pylori populations than patients with peptic ulcer disease. […] H. pylori causes gastric disease owing to its production of vacuolating cytotoxin and to a pathogenicity island-encoded type IV secretion system; both virulence determinants act together to promote the production of pro-inflammatory cytokines, to disrupt cell polarity and to cause tissue damage. The advantage of producing these virulence determinants for the bacterium remains poorly understood, but might involve improved iron acquisition or enhanced transmission.

• #32 Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori | Nature Reviews Microbiology

  https://www.nature.com/articles/nrmicro3016

  The bacterial pathogen H. pylori has co-evolved with humans and colonizes approximately 50% of the human population, but only causes overt gastric disease in a subset of infected hosts. In this Review, we discuss the pathogenesis of H. pylori and the mechanisms it uses to promote persistent colonization of the gastric mucosa, with a focus on recent insights into the role of the virulence factors vacuolating cytotoxin (VacA), cytotoxin-associated gene A (CagA) and CagL. We also describe the immunobiology of H. pylori infection and highlight how this bacterium manipulates the innate and adaptive immune systems of the host to promote its own persistence.

• #33

  https://www.alliedacademies.org/articles/helicobacter-pylori-pathogenesis-and-its-role-in-gastrointestinal-disorders-30767.html

  Helicobacter pylori (H. pylori) are a gram-negative bacterium that colonizes the gastric epithelium and is a major contributor to various gastrointestinal disorders. Its pathogenesis involves complex interactions with the hosts immune system, gastric mucosa, and environmental factors. H. pylori infection is prevalent worldwide, and while many infected individuals remain asymptomatic, it can lead to significant health issues. […] The bacterium adheres to the gastric epithelium using adhesins, which facilitate its colonization and persistence in the acidic environment of the stomach. H. pylori produces urease, an enzyme that converts urea into ammonia and carbon dioxide, helping to neutralize gastric acid and create a more hospitable environment. This ability to alter the local pH allows it to survive and thrive in the stomach, leading to chronic inflammation or chronic gastritis.

• #34 Helicobacter pylori: pathogenesis – Microb Health Dis

  https://www.microbiotajournal.com/article/1046

  In this review, we analyze the research articles and findings related to the pathogenesis of Helicobacter pylori infection, which were published between April 2023 and March 2024. H. pylori is the most common infectious disease worldwide. The clinical consequences of H. pylori infection are closely linked with the expression of virulence factors produced by the bacterium. To improve diagnostic tools and optimize the treatment outcomes of H. pylori infection it is essential to understand its pathogenesis. The latest mechanisms of how H. pylori interact with host tissue and microbiome, induces and modulates its pathogenicity, and influences the development of malignant disease as well as extragastric pathologies are represented in our review article. […] The mechanisms of resistance are still in the scope of research. We also describe the studies related to the possible mechanisms of resistance of H. pylori to antibacterial drugs.

• #35 Review: Pathogenesis of Helicobacter pylori infection. – Research – Institut Pasteur

  https://research.pasteur.fr/en/publication/review-pathogenesis-of-helicobacter-pylori-infection/

  The original strategies developed by Helicobacter pylori to persistently colonise its host and to deregulate its cellular functions make this bacterium an outstanding model to study host-pathogen interaction and the mechanisms responsible for bacterial-induced carcinogenesis. […] Several studies further characterised the role of CagA in the oncogenic properties of H pylori, identifying the activation of novel CagA-dependent pathways, leading to the promotion of genetic instabilities, epithelial-to-mesenchymal transition and finally carcinogenesis. […] Recent studies also highlight that microRNA-mediated regulation and epigenetic modifications, through DNA methylation, are key events in the H pylori-induced tumorigenesis process.

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