Helicobacter Pylori - Literature review Example

Helicobacter pylori General overview of bacterium. Helicobacter pylori is a Gram-negative microaerophilic bacterium with curved or spiral shape and a lot of flagella. This bacterium has been found in the gastric pits and on the surface of epithelial cells, mainly under the protective mucous layer lining the gastric mucosa (Kelly). Due to such an unusual environment, Helicobacter pylori have no competition from other microorganisms. Helicobacter pylori environment`s pH is approximately 7, the concentration of oxygen is low and the nutrient content is quite sufficient for microbial existence (Kelly; Marshall). Virulence. Today there are several virulence factors allowing Helicobacter pylori colonize and then persist in the host organism: • Spiral shape and the presence of flagella • The presence of adaptation enzymes • Adhesivity • Immunosuppression. Spiral shape and the presence of flagella. Helicobacter pylori spiral shape is well adapted to the movement inside the viscous gastric mucus layer that allows the microorganism to completely colonize the mucosa. Furthermore, the presence of coated flagella allows bacteria to move fast in the gastric juice as well as in the mucus (Marshall). Adaptation enzymes. Helicobacter pylori produce two main adaptation enzymes - urease and catalase. The urease is contained in gastric juice and catalyzes urea into carbon dioxide (CO2) and ammonium ion (NH4+), which further neutralize the pH of the immediate environment of the microbe and protects Helicobacter pylori against bactericidal action of gastric acid. Thus, the microorganism preserved in gastric juice penetrates into the protective layer of mucus on the surface of the gastric epithelium. Secretion of catalase and possibly superoxide dismutase allows Helicobacter pylori to suppress the immune response of the host (Kalali et al.). These enzymes catalyze the transformation of compounds of bactericidal oxygen (which are released by activated neutrophils) into harmless substances such as oxygen and water. Adhesivity. The ability of Helicobacter pylori to attach specific oligosaccharide components of glycoproteins and phospholipids in the membranes of gastric epithelial cells determines its selective colonization of mucus-secreting cells. In those places where the bacterial cell membranes are adjacent to each other, the disruption of microvilli and the rupture of components of the cytoskeleton is observed (Kelly). Other possible binding receptors can be extracellular matrix components, such as laminin, fibronectin and various types of collagen. It is believed that only a very small amount of the microorganisms (less than 10%) existing in the stomach is bound at any particular time. Concerning the necessity of Helicobacter pylori adhesion there is no single point of view, and even if adhesion is not an obligatory condition for colonization of the gastric mucosa, it can be considered as an extremely important stage in the development of the disease (Kalali et al.). Symptoms. In many cases, the infection may be asymptomatic. Detection of Helicobacter pylori in the absence of inflammatory diseases of the stomach or intestines is not an indication for antibiotic therapy. Helicobacter pylori infection can be the cause of the different inflammatory diseases, such as gastric or duodenal ulcer, erosive gastritis and gastroduodenitis (Talebi Bezmin Abadi). Immunosuppression. Helicobacter pylori stimulate the immune system of the host organism to develop antibodies. However, as shown by the results of the studies, the microorganisms are capable to suppress cellular immune responses (Ricci, Romano, and Boquet). Protection against infection is commonly carried by phagocytes. These white blood cells are able to capture and digest harmful foreign particles, like dead cells or bacteria. Under normal circumstances, due to hemagglutinin actions phagocytes cannot pass through the stomach lining. Hemagglutinin is located on the outer membrane of Helicobacter pylori cells and can slow down the process of adhesion or phagocytosis by polymorphonuclear leukocytes. Furthermore, the ammonia produced by Helicobacter pylori is capable to damage the membrane of phagocytes. As already mentioned, the catalase activity of Helicobacter pylori also allows the bacteria escape from the destructive effects of neutrophils (Ricci, Romano, and Boquet). Lipopolysaccharides act as a hydrophilic barrier associated with the bacterial cell surface. Helicobacter pylori lipopolysaccharides were formed during an evolution to protect bacteria from overactive immune response that allows the microorganism to survive in the stomach. Taken from patients with ulcer, lipopolysaccharides of Helicobacter pylori can stimulate the secretion of pepsinogen that leads to an excess of pepsin, which is a risk factor in the development of peptic ulcer disease (Ricci, Romano, and Boquet). Virulence factors. About 65% of all Helicobacter pylori strains produces vacuolating cytotoxin (VacA), which promotes the formation of vacuoles in epithelial cells (Chen, Yan, and Shen). Almost all patients with duodenal ulcers infected by VacA-forming strain of Helicobacter pylori. Cytotoxic activity is higher in those microorganisms that have been obtained from patients with duodenal ulcers, compared to those that were taken from persons who do not suffer from peptic ulcer. VacA-forming Helicobacter pylori strains also produce cytotoxin-associated protein A (CagA). Antibodies to CagA were found in the serum of almost all patients with carcinoma and gastric ulcer (Chen, Yan, and Shen). Urease. Usually urease activity can be associated with toxic effects of produced ammonia. At high concentration, ammonia causes vacuolation of epithelial cells (Ricci, Romano, and Boquet). Phospholipases A2 and C. It is known that gastric epithelial cell membranes are composed of two layers of phospholipids. Changes in the layers of phospholipids caused by Helicobacter pylori phospholipases A2 and C are observed in vitro. Phospholipases from the lysate of bacteria convert the hydrophobic surface of the phospholipid layer in "wet" hydrophilic state. Thus, as a result of these bacterial enzymes action the integrity of epithelial cell membranes and their resistance to damage is violated. Mucus viscosity and hydrophobicity equally depend on its content of phospholipids. In the presence of Helicobacter pylori, mucus becomes less hydrophobic and its viscosity decreases (Chen, Yan, and Shen). Due to these changes the mucous membrane of the stomach lumen receives a large amount of hydrogen ions, which causes damage. Stimulation of inflammation. Inflammatory reactions, which proceed in the host in response to the introduction of Helicobacter pylori, promote the disruption of gastric epithelium cells integrity. Chemotaxis proteins released by bacteria, attract large numbers of neutrophils, monocytes, and lymphocytes (Ricci, Romano, and Boquet). Thus, the presence of a large number of neutrophils in the epithelium of the stomach is typical for Helicobacter pylori infection. Mononuclear cells secrete interleukins, tumor necrosis factors and superoxide radicals. Interleukins and tumor necrosis factor do not allow the mononuclear cells to migrate from the site of the inflammatory reaction. Moreover, they trigger the production of superoxide radicals, which are then converted into other active oxygen metabolites that are toxic for Helicobacter pylori as well as for mucosal cells. Epidemiology. Helicobacter pylori infection usually occurs in childhood and in the absence of treatment persists in the body indefinitely. The frequency of infection among children from 2 to 8 years of age in developing countries is 10% per year and reaches almost 100% in adulthood. In developed countries, the prevalence of Helicobacter pylori also increases with age, but the infection among children is relatively low (Kusters, van Vliet, and Kuipers). Besides, the social and economic situation is an important epidemiological factor for Helicobacter pylori infection. In general, low socio-economic status of the population increases the risk of infection. It has been suggested that the prevalence of the children population in society is the only significant risk factor; however, the access to safe drinking water and compliance with health standards is also important in the prevention of Helicobacter pylori infection (Marshall). Treatment. Currently, the identification of Helicobacter pylori requires an eradication therapy only if there is clear indications for it (for example in the presence of peptic ulcer disease). The "gold standard" in Helicobacter pylori eradication is a combination of colloidal bismuth subcitrate (within 4 weeks) with antibacterial agents (amoxicillin and metronidazole or tetracycline) during the first two weeks of treatment. This treatment regimen showed high efficiency in Helicobacter pylori eradication; however, due to a high frequency of side effects and a complex drug reception circuit such treatment cannot be considered as ideal and can cause the patient`s refusal of treatment (Talebi Bezmin Abadi). Antibiotic resistance. Helicobacter pylori antibiotic resistance is a growing problem in the modern eradication therapy (Jenks and Edwards). Resistance can be divided into primary (innate) and secondary (acquired) types: • Primary resistance is provided by Helicobacter pylori strains, which are resistant at the start of eradication therapy • Secondary type implies resistance that has developed during the unsuccessful eradication therapy Resistance to metronidazole is often associated with treatment failure. The dramatic geographical differences in the frequency of resistance to metronidazole are observed. This fact reflects the different latitudes of using this drug in different countries. Research indicates that Helicobacter pylori resistance to metronidazole in the world is increasing and in some countries can reach over 80% resistant strains. Helicobacter pylori resistance to other antibiotics (including clarithromycin) also found, but it is generally less (for clarithromycin in Western Europe about 5-10% of resistant strains are observed) (Jenks and Edwards). Works Cited Chen, Xue-Jun, Jie Yan, and Yue-Fang Shen. “Dominant cagA/vacA Genotypes and Coinfection Frequency of H. Pylori in Peptic Ulcer or Chronic Gastritis Patients in Zhejiang Province and Correlations among Different Genotypes, Coinfection and Severity of the Diseases.” Chinese medical journal 118.6 (2005): 460–7. Web. 26 Mar. 2015. Jenks, Peter J, and David I Edwards. “Metronidazole Resistance in Helicobacter Pylori.” International journal of antimicrobial agents 19.1 (2002): 1–7. Web. 26 Mar. 2015. Kalali, Behnam et al. “H. Pylori Virulence Factors: Influence on Immune System and Pathology.” Mediators of inflammation 2014 (2014): 426309. Web. 5 Mar. 2015. Kelly, D J. “The Physiology and Metabolism of the Human Gastric Pathogen Helicobacter Pylori.” Advances in microbial physiology 40 (1998): 137–89. Web. 26 Mar. 2015. Kusters, Johannes G, Arnoud H M van Vliet, and Ernst J Kuipers. “Pathogenesis of Helicobacter Pylori Infection.” Clinical microbiology reviews 19.3 (2006): 449–90. Web. 14 July 2014. Marshall, Barry. “Helicobacter Pylori: 20 Years On.” Clinical medicine (London, England) 2.2 147–52. Web. 17 Feb. 2015. Ricci, Vittorio, Marco Romano, and Patrice Boquet. “Molecular Cross-Talk between Helicobacter Pylori and Human Gastric Mucosa.” World journal of gastroenterology : WJG 17.11 (2011): 1383–99. Web. 26 Mar. 2015. Talebi Bezmin Abadi, Amin. “Therapy of Helicobacter Pylori: Present Medley and Future Prospective.” BioMed research international 2014 (2014): 124607. Web. 26 Mar. 2015.  Read More