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      Strategies used by helicobacter pylori to establish persistent infection

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          Abstract

          Helicobacter pylori ( H. pylori) is a Gram-negative and motile bacterium that colonizes the hostile microniche of the human stomach, then persists for the host’s entire life, if not effectively treated. Clinically, H. pylori plays a causative role in the development of a wide spectrum of diseases including chronic active gastritis, peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Due to the global distribution of H. pylori, it is no exaggeration to conclude that smart strategies are contributing to adaptation of the bacterium to its permanent host. Thirty-four years after the discovery of this bacterium, there are still many unanswered questions. For example, which strategies help the bacterium to survive in this inhospitable microniche? This question is slightly easier to answer if we presume the same clinical concept for both persistent infection and disease. Understanding the mechanisms governing H. pylori persistence will improve identification of the increased risk of diseases such as gastric cancer in patients infected with this bacterium. A well-defined and long-term equilibrium between the human host and H. pylori allows bacterial persistence in the gastric microniche; although this coexistence leads to a high risk of severe diseases such as gastric cancer. To escape the bactericidal activity of stomach acid, H. pylori secretes large amounts of surface-associated and cytosolic urease. The potential to avoid acidic conditions and immune evasion are discussed in order to explain the persistence of H. pylori colonization in the gastric mucosa, and data on bacterial genetic diversity are included. Information on the mechanisms related to H. pylori persistence can also provide the direction for future research concerning effective therapy and management of gastroduodenal disorders. The topics presented in the current review are important for elucidating the strategies used by H. pylori to help the bacterium persist in relation to the immune system and the many unfavorable features of living in the gastric microniche.

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          American College of Gastroenterology guideline on the management of Helicobacter pylori infection.

          Helicobacter pylori (H. pylori) remains a prevalent, worldwide, chronic infection. Though the prevalence of this infection appears to be decreasing in many parts of the world, H. pylori remains an important factor linked to the development of peptic ulcer disease, gastric malignanc and dyspeptic symptoms. Whether to test for H. pylori in patients with functional dyspepsia, gastroesophageal reflux disease (GERD), patients taking nonsteroidal antiinflammatory drugs, with iron deficiency anemia, or who are at greater risk of developing gastric cancer remains controversial. H. pylori can be diagnosed by endoscopic or nonendoscopic methods. A variety of factors including the need for endoscopy, pretest probability of infection, local availability, and an understanding of the performance characteristics and cost of the individual tests influences choice of evaluation in a given patient. Testing to prove eradication should be performed in patients who receive treatment of H. pylori for peptic ulcer disease, individuals with persistent dyspeptic symptoms despite the test-and-treat strategy, those with H. pylori-associated MALT lymphoma, and individuals who have undergone resection of early gastric cancer. Recent studies suggest that eradication rates achieved by first-line treatment with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin have decreased to 70-85%, in part due to increasing clarithromycin resistance. Eradication rates may also be lower with 7 versus 14-day regimens. Bismuth-containing quadruple regimens for 7-14 days are another first-line treatment option. Sequential therapy for 10 days has shown promise in Europe but requires validation in North America. The most commonly used salvage regimen in patients with persistent H. pylori is bismuth quadruple therapy. Recent data suggest that a PPI, levofloxacin, and amoxicillin for 10 days is more effective and better tolerated than bismuth quadruple therapy for persistent H. pylori infection, though this needs to be validated in the United States.
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            Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens.

            Toll-like receptor (TLR) signaling in macrophages is required for antipathogen responses, including the biosynthesis of nitric oxide from arginine, and is essential for immunity to Mycobacterium tuberculosis, Toxoplasma gondii and other intracellular pathogens. Here we report a 'loophole' in the TLR pathway that is advantageous to these pathogens. Intracellular pathogens induced expression of the arginine hydrolytic enzyme arginase 1 (Arg1) in mouse macrophages through the TLR pathway. In contrast to diseases dominated by T helper type 2 responses in which Arg1 expression is greatly increased by interleukin 4 and 13 signaling through the transcription factor STAT6, TLR-mediated Arg1 induction was independent of the STAT6 pathway. Specific elimination of Arg1 in macrophages favored host survival during T. gondii infection and decreased lung bacterial load during tuberculosis infection.
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              Helicobacter pylori persistence: biology and disease.

              Helicobacter pylori are bacteria that have coevolved with humans to be transmitted from person to person and to persistently colonize the stomach. Their population structure is a model for the ecology of the indigenous microbiota. A well-choreographed equilibrium between bacterial effectors and host responses permits microbial persistence and health of the host but confers risk of serious diseases, including peptic ulceration and gastric neoplasia.
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                Author and article information

                Journal
                World J Gastroenterol
                World J. Gastroenterol
                WJG
                World Journal of Gastroenterology
                Baishideng Publishing Group Inc
                1007-9327
                2219-2840
                28 April 2017
                28 April 2017
                : 23
                : 16
                : 2870-2882
                Affiliations
                Amin Talebi Bezmin Abadi, Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14115-111, Iran
                Author notes

                Author contributions: Talebi Bezmin Abadi A designed the research, analyzed the data and wrote the article.

                Correspondence to: Amin Talebi Bezmin Abadi, PhD, Assistant Professor, Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14115-111, Iran. amin.talebi@ 123456modares.ac.ir

                Telephone: +98-21-82884883 Fax: +98-21-82884883

                Article
                jWJG.v23.i16.pg2870
                10.3748/wjg.v23.i16.2870
                5413782
                28522905
                48df019f-1df2-4e5e-8b17-6277ac35dfb5
                ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 5 December 2016
                : 1 February 2017
                : 16 February 2017
                Categories
                Review

                helicobacter pylori,gastric microniche,persistent infection,gastric cancer

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