Thibonnier, Marie; Thiberge, Jean-Michel; De Reuse, Hilde
The ubiquitous bacterial trans-translation is one of the most studied quality control mechanisms. Trans-translation requires two specific factors, a small RNA SsrA (tmRNA) and a protein co-factor SmpB, to promote the release of ribosomes stalled on defective mRNAs and to add a specific tag sequence to aberrant polypeptides to direct them to degradation pathways. Helicobacter pylori is a pathogen persistently colonizing a hostile niche, the stomach of humans. We investigated the role of trans-translation in this bacterium well fitted to resist stressful conditions and found that both smpB and ssrA were essential genes. Five mutant versions of ssrA were generated in H. pylori in order to investigate the function of trans-translation in this organism. Mutation of the resume codon that allows the switch of template of the ribosome required for its release was essential in vivo, however a mutant in which this codon was followed by stop codons interrupting the tag sequence was viable. Therefore one round of translation is sufficient to promote the rescue of stalled ribosomes. A mutant expressing a truncated SsrA tag was viable in H. pylori, but affected in competence and tolerance to both oxidative and antibiotic stresses. This demonstrates that control of protein degradation through trans-translation is by itself central in the management of stress conditions and of competence and supports a regulatory role of trans-translation-dependent protein tagging. In addition, the expression of smpB and ssrA was found to be induced upon acid exposure of H. pylori. We conclude to a central role of trans-translation in H. pylori both for ribosome rescue possibly due to more severe stalling and for protein degradation to recover from stress conditions frequently encountered in the gastric environment. Finally, the essential trans-translation machinery of H. pylori is an excellent specific target for the development of novel antibiotics.
Thibonnier, Marie; Thiberge, Jean-Michel; De Reuse, Hilde
Background The ubiquitous bacterial trans-translation is one of the most studied quality control mechanisms. Trans-translation requires two specific factors, a small RNA SsrA (tmRNA) and a protein co-factor SmpB, to promote the release of ribosomes stalled on defective mRNAs and to add a specific tag sequence to aberrant polypeptides to direct them to degradation pathways. Helicobacter pylori is a pathogen persistently colonizing a hostile niche, the stomach of humans. Principal Findings We investigated the role of trans-translation in this bacterium well fitted to resist stressful conditions and found that both smpB and ssrA were essential genes. Five mutant versions of ssrA were generated in H. pylori in order to investigate the function of trans-translation in this organism. Mutation of the resume codon that allows the switch of template of the ribosome required for its release was essential in vivo, however a mutant in which this codon was followed by stop codons interrupting the tag sequence was viable. Therefore one round of translation is sufficient to promote the rescue of stalled ribosomes. A mutant expressing a truncated SsrA tag was viable in H. pylori, but affected in competence and tolerance to both oxidative and antibiotic stresses. This demonstrates that control of protein degradation through trans-translation is by itself central in the management of stress conditions and of competence and supports a regulatory role of trans-translation-dependent protein tagging. In addition, the expression of smpB and ssrA was found to be induced upon acid exposure of H. pylori. Conclusions We conclude to a central role of trans-translation in H. pylori both for ribosome rescue possibly due to more severe stalling and for protein degradation to recover from stress conditions frequently encountered in the gastric environment. Finally, the essential trans-translation machinery of H. pylori is an excellent specific target for the development of novel antibiotics. PMID
Shpanchenko, Olga V; Golovin, Andrey V; Bugaeva, Elizaveta Y; Isaksson, Leif A; Dontsova, Olga A
trans-Translation is a process which the bacterial cells apply to rescue the ribosomes that are arrested during the translation of damaged mRNA and to get rid of the mRNA and the product polypeptide. In the course of trans-translation, the mRNA-like domain of tmRNA replaces the nonstop messenger RNA bound to the ribosome. Although several structural elements of tmRNA and SmpB known to be essential for correct determination of resume codon, the molecular mechanism of trans-translation is not well understood. Computer modeling has been used to develop a model for the spatial organization of the tmRNA inside the ribosome at different stages of trans-translation leading to a proposal for the mechanism of the template-switching process. (c) 2010 IUBMB IUBMB Life.
Brunel, Romain; Charpentier, Xavier
Trans-translation is a ubiquitous bacterial mechanism for ribosome rescue in the event of translation stalling. Although trans-translation is not essential in several bacterial species, it has been found essential for viability or virulence in a wide range of pathogens. We describe here that trans-translation is essential in the human pathogen Legionella pneumophila, the etiologic agent of Legionnaire's disease (LD), a severe form of nosocomial and community-acquired pneumonia. The ssrA gene coding for tmRNA, the key component of trans-translation, could not be deleted in L. pneumophila. To circumvent this and analyse the consequences of impaired trans-translation, we placed ssrA under the control of a chemical inducer. Phenotypes associated with the inhibition of ssrA expression include growth arrest in rich medium, hampered cell division, and hindered ability to infect eukaryotic cells (amoebae and human macrophages). LD is often associated with failure of antibiotic treatment and death (>10% of clinical cases). Decreasing tmRNA levels led to significantly higher sensitivity to ribosome-targeting antibiotics, including to erythromycin. We also detected a higher sensitivity to the transcription inhibitor rifampicin. Both antibiotics are recommended treatments for LD. Thus, interfering with trans-translation may not only halt the infection, but could also potentiate the recommended therapeutic treatments of LD.
Brunel, Romain; Charpentier, Xavier
Trans-translation is a ubiquitous bacterial mechanism for ribosome rescue in the event of translation stalling. Although trans-translation is not essential in several bacterial species, it has been found essential for viability or virulence in a wide range of pathogens. We describe here that trans-translation is essential in the human pathogen Legionella pneumophila, the etiologic agent of Legionnaire’s disease (LD), a severe form of nosocomial and community-acquired pneumonia. The ssrA gene coding for tmRNA, the key component of trans-translation, could not be deleted in L. pneumophila. To circumvent this and analyse the consequences of impaired trans-translation, we placed ssrA under the control of a chemical inducer. Phenotypes associated with the inhibition of ssrA expression include growth arrest in rich medium, hampered cell division, and hindered ability to infect eukaryotic cells (amoebae and human macrophages). LD is often associated with failure of antibiotic treatment and death (>10% of clinical cases). Decreasing tmRNA levels led to significantly higher sensitivity to ribosome-targeting antibiotics, including to erythromycin. We also detected a higher sensitivity to the transcription inhibitor rifampicin. Both antibiotics are recommended treatments for LD. Thus, interfering with trans-translation may not only halt the infection, but could also potentiate the recommended therapeutic treatments of LD. PMID:27892503
Ivanova, Natalia; Lindell, Magnus; Pavlov, Michael; Holmberg Schiavone, Lovisa; Wagner, E. Gerhart H.; Ehrenberg, Måns
Ribosomes stalled on problematic mRNAs in bacterial cells can be rescued by transfer-messenger RNA (tmRNA), its helper protein (small protein B, SmpB), and elongation factor Tu (EF-Tu) through a mechanism called trans-translation. In this work we used lead(II) footprinting to probe the interactions of tmRNA with SmpB and other components of the translation machinery at different steps of the trans-translation cycle. Ribosomes with a short nascent peptide stalled on a truncated mRNA were reacted with Ala-tmRNA•EF-Tu•GTP, SmpB, and other translation components to initiate and execute trans-translation. Free tmRNA was probed with lead(II) acetate with and without SmpB, and ribosome bound tmRNA was probed in one of four different trans-translation states stabilized by antibiotic addition or selective exclusion of translation components. For comparison, we also analyzed lead(II) cleavage patterns of tmRNA in vivo in a wild-type as well as in an SmpB-deficient Escherichia coli strain. We observed some specific cleavages/protections in tmRNA for the individual steps of trans-translation, but the overall tmRNA conformation appeared to be similar in the stages analyzed. Our findings suggest that, in vivo, a dominant fraction of tmRNA is in complex with SmpB and that, in vitro, SmpB remains tmRNA bound at the initial steps of trans-translation. PMID:17400816
Takada, Kazuma; Takemoto, Chie; Kawazoe, Masahito; Shirouzu, Mikako; Yokoyama, Shigeyuki; Muto, Akira; Himeno, Hyouta
In trans-translation, ribosome switches the template for protein synthesis from an mRNA to tmRNA. The molecular mechanism of trans-translation remains mysterious. In order to clarify how tmRNA move through the ribosome, we developed in vitro systems to monitor trans-translation as well as translation, which are composed of ribosome, elongation factors, tmRNA and SmpB all from Thermus thermophilus. In these systems, the early steps of trans-translation including trans-transfer and the resume codon decoding could be monitored. Using these systems, the function of ribosomal protein S1 which has been suggested to be involved in trans-translation was investigated.
Shi, Wanliang; Zhang, Xuelian; Jiang, Xin; Yuan, Haiming; Lee, Jong Seok; Barry, Clifton E; Wang, Honghai; Zhang, Wenhong; Zhang, Ying
Pyrazinamide (PZA) is a first-line tuberculosis drug that plays a unique role in shortening the duration of tuberculosis chemotherapy. PZA is hydrolyzed intracellularly to pyrazinoic acid (POA) by pyrazinamidase (PZase, encoded by pncA), an enzyme frequently lost in PZA-resistant strains, but the target of POA in Mycobacterium tuberculosis has remained elusive. Here, we identify a previously unknown target of POA as the ribosomal protein S1 (RpsA), a vital protein involved in protein translation and the ribosome-sparing process of trans-translation. Three PZA-resistant clinical isolates without pncA mutation harbored RpsA mutations. RpsA overexpression conferred increased PZA resistance, and we confirmed that POA bound to RpsA (but not a clinically identified ΔAla mutant) and subsequently inhibited trans-translation rather than canonical translation. Trans-translation is essential for freeing scarce ribosomes in nonreplicating organisms, and its inhibition may explain the ability of PZA to eradicate persisting organisms.
Michalkiewicz, Jacek; Helmin-Basa, Anna; Grzywa, Renata; Czerwionka-Szaflarska, Mieczyslawa; Szaflarska-Poplawska, Anna; Mierzwa, Grazyna; Marszalek, Andrzej; Bodnar, Magdalena; Nowak, Magdalena; Dzierzanowska-Fangrat, Katarzyna
PURPOSE. To investigate the expression of innate immunity components and cytokines in the gastric mucosa among H. pylori infected and uninfected children. Materials and Methods. Biopsies of the antral gastric mucosa from children with dyspeptic symptoms were evaluated. Gene expressions of innate immunity receptors and cytokines were measured by quantitative real-time PCR. The protein expression of selected molecules was tested by immunohistochemistry. RESULTS. H. pylori infection did not lead to a significant upregulation of MyD88, TLR2, TLR4, CD14, TREM1, and TREM2 mRNA expression but instead resulted in high mRNA expression of IL-6, IL-10, IFN-γ, TNF-α, and CD163. H. pylori cagA(+) infection was associated with higher IL-6 and IL-10 mRNA expression, as compared to cagA(-) strains. H. pylori infected children showed increased IFN-γ and TNF-α protein levels. IFN-γ mRNA expression correlated with both H. pylori density of colonization and lymphocytic infiltration in the gastric mucosa, whereas TNF-α protein expression correlated with bacterial density. CONCLUSION. H. pylori infection in children was characterized by (a) Th1 expression profile, (b) lack of mRNA overexpression of natural immunity receptors, and (c) strong anti-inflammatory activities in the gastric mucosa, possibly resulting from increased activity of anti-inflammatory M2 macrophages. This may explain the mildly inflammatory gastric inflammation often observed among H. pylori infected children.
Background Ribonuclease R (RNase R) is an exoribonuclease that recognizes and degrades a wide range of RNA molecules. It is a stress-induced protein shown to be important for the establishment of virulence in several pathogenic bacteria. RNase R has also been implicated in the trans-translation process. Transfer-messenger RNA (tmRNA/SsrA RNA) and SmpB are the main effectors of trans-translation, an RNA and protein quality control system that resolves challenges associated with stalled ribosomes on non-stop mRNAs. Trans-translation has also been associated with deficiencies in stress-response mechanisms and pathogenicity. Results In this work we study the expression of RNase R in the human pathogen Streptococcus pneumoniae and analyse the interplay of this enzyme with the main components of the trans-translation machinery (SmpB and tmRNA/SsrA). We show that RNase R is induced after a 37°C to 15°C temperature downshift and that its levels are dependent on SmpB. On the other hand, our results revealed a strong accumulation of the smpB transcript in the absence of RNase R at 15°C. Transcriptional analysis of the S. pneumoniae rnr gene demonstrated that it is co-transcribed with the flanking genes, secG and smpB. Transcription of these genes is driven from a promoter upstream of secG and the transcript is processed to yield mature independent mRNAs. This genetic organization seems to be a common feature of Gram positive bacteria, and the biological significance of this gene cluster is further discussed. Conclusions This study unravels an additional contribution of RNase R to the trans-translation system by demonstrating that smpB is regulated by this exoribonuclease. RNase R in turn, is shown to be under the control of SmpB. These proteins are therefore mutually dependent and cross-regulated. The data presented here shed light on the interactions between RNase R, trans-translation and cold-shock response in an important human pathogen. PMID:23167513
Mirzaei, Nasrin; Poursina, Farkhondeh; Moghim, Sharareh; Rashidi, Niloufar; Ghasemian Safaei, Hajieh
Helicobacter pylori has grown to colonize inside the stomach of nearly half of the world's population, turning into the most prevalent infections in the universe. Medical care failures noticeably confirm the need for a vaccine to hinder or deal with H. pylori. This review is planned to discuss the most known factors as a vaccine candidate, including single (AhpC, BG, CagA, KatA, Fla, Hsp, HWC, Lpp, LPS, NAP, OMP, OMV, SOD, Tpx, Urease, VacA) and multi-component vaccines. Many promising results in the field of single and multivalent vaccine can be seen, but there is no satisfactory outcome and neither a prophylactic nor a therapeutic vaccine to treat or eradicate the infection in human has been acquired. Hence, selecting suitable antigen is an important factor as an appropriate adjuvant. Taken all together, the development of efficient anti-H. pylori vaccines relies on the fully understanding of the interactions between H. pylori and its host immune system. Therefore, more work should be done on epitope mapping, analysis of molecular structure, and determination of the antigen determinant region as well due to design a vaccine, preferably a multi-component vaccine to elicit specific CD4 T-cell responses that are required for H. pylori vaccine efficacy.
Venkataraman, Krithika; Guja, Kip E; Garcia-Diaz, Miguel; Karzai, A Wali
Decoding of aberrant mRNAs leads to unproductive ribosome stalling and sequestration of components of the translation machinery. Bacteria have evolved three seemingly independent pathways to resolve stalled translation complexes. The trans-translation process, orchestrated by the hybrid transfer-messenger RNA (tmRNA) and its essential protein co-factor, small protein B (SmpB), is the principal translation quality control system for rescuing unproductively stalled ribosomes. Two specialized alternative rescue pathways, coordinated by ArfA and ArfB, have been recently discovered. The SmpB-tmRNA mediated trans-translation pathway, in addition to re-mobilizing stalled translation complexes, co-translationally appends a degradation tag to the associated nascent polypeptides, marking them for proteolysis by various cellular proteases. Another unique feature of trans-translation, not shared by the alternative rescue pathways, is the facility to recruit ribonuclease R (RNase R) for targeted degradation of non-stop mRNAs, thus preventing further futile cycles of translation. The distinct C-terminal lysine-rich (K-rich) domain of RNase R is essential for its recruitment to stalled ribosomes. To gain new insights into the structure and function of RNase R, we investigated its global architecture, the spatial arrangement of its distinct domains, and the identities of key functional residues in its unique K-rich domain. Small-angle X-ray scattering models of RNase R reveal a tri-lobed structure with flexible N- and C-terminal domains, and suggest intimate contacts between the K-rich domain and the catalytic core of the enzyme. Alanine-scanning mutagenesis of the K-rich domain, in the region spanning residues 735 and 750, has uncovered the precise amino acid determinants required for the productive engagement of RNase R on tmRNA-rescued ribosomes. Theses analyses demonstrate that alanine substitution of conserved residues E740 and K741result in profound defects, not only in the
Domingues, Susana; Moreira, Ricardo N; Andrade, José M; Dos Santos, Ricardo F; Bárria, Cátia; Viegas, Sandra C; Arraiano, Cecília M
Gene expression not only depends on the rate of transcription but is also largely controlled at the post-transcriptional level. Translation rate and mRNA decay greatly influence the final protein levels. Surveillance mechanisms are essential to ensure the quality of the RNA and proteins produced. Trans-translation is one of the most important systems in the quality control of bacterial translation. This process guarantees the destruction of abnormal proteins and also leads to degradation of the respective defective RNAs through the action of Ribonuclease R (RNase R). This exoribonuclease hydrolyzes RNAs starting from their 3' end. Besides its involvement in trans-translation, RNase R also participates in the quality control of rRNA molecules involved in ribosomal biogenesis. RNase R is thus emerging as a key factor in ensuring translation accuracy. This review focuses on issues related to the quality control of translation, with special emphasis on the role of RNase R.
Liu, Jian-Hui; Li, Liang; Shang, Xiao-Dong; Zhang, Jun-Ling; Tan, Qi
The fungus Hericium erinaceus (Bull.) Pers is used in Chinese traditional medicine to treat symptoms related to gastric ulcers. Different extracts from the fungus were assessed for anti-Helicobacter pylori activity to investigate the antibacterial activity of the ethanol extracts from H. erinaceus and verify the traditional indication of use. The fruiting bodies of H. erinaceus were concentrated with ethanol by HPD-100 macroporous resin and the whole extract was partitioned by petroleum ether and chloroform to afford fractions with using a silica gel column. Several pure compounds of petroleum ether extracts were obtained and analyzed using nuclear magnetic resonance (NMR). The activity of the extracts and fractions towards H. pylori was assessed by the microdilution assay and by the disk diffusion assay in vitro. From the most active fraction, two pure compounds were isolated and identified as the main components with anti-H. pylori activity from the fungus H. erinaceus. The cytotoxicity of these two compounds against the human erythroleu-kemia cell line K562 was also evaluated. The crude ethanol extracts from the fungus H. erinaceus were inhibitory to H. pylori. The petroleum ether extracts (PE1s, PE2s) and the chloroform extracts (TEs) demonstrated strong inhibition to H. pylori. The inhibition of H. pylori was observed through an agar dilution test with minimal inhibition concentration (MIC) values from 400μg/mL to 12.5µg/mL. Two pure compounds, 1-(5-chloro-2-hydroxyphenyl)-3-methyl-1-butanone and 2,5-bis(methoxycarbonyl)terephthalic acid were isolated from the petroleum ether fractions and identified using (1)H NMR and (13)C NMR spectra analysis. The MIC value for 1-(5-chloro-2-hydroxyphenyl)-3-methyl-1-butanone was 12.5-50µg/mL and the MIC value for 2,5-bis(methoxycarbonyl)terephthalic acid was 6.25-25µg/mL. Both two compounds showed weak cytotoxicity against K562 with IC50<200mM. This study revealed that the extracts from petroleum ether contribute to
Merino, Enrique; Flores-Encarnación, Marcos; Aguilar-Gutiérrez, Germán Rubén
The Helicobacter pylori infection of the human gastric mucosa causes chronic active gastritis and peptic ulcers and is associated with the development of gastric cancer. Epidemiological studies show that these gastric diseases are related to virulent H. pylori strains that harbor the cytotoxin-associated gene pathogenicity island (cag PAI). The cag PAI is a DNA insertion in the H. pylori chromosome that encodes ~ 27 proteins, including the oncoprotein CagA. Approximately 20 of these proteins have been designated as cag type IV secretion system (T4SS) components. However, only 11 of these proteins share function, structure, and/or sequence similarities with the prototypical VirB/VirD4 T4SS of Agrobacterium tumefaciens. The VirB/VirD4 orthologs of the cag T4SS of H. pylori are required for CagA translocation and stimulate the gastric epithelial cells to produce and secrete interleukin-8 (IL-8). The cag PAI encodes eight additional proteins, such as Cag3 (Cagδ/HP0522), CagM (Cag16/HP0537), CagU (Cag11/HP0531), CagI (Cag19/HP0540), and CagH (Cag20/HP0541), which are also required for the translocation of CagA and IL-8 secretion, meanwhile CagF (Cag22/HP0543), CagG (Cag21/HP0542), and CagZ (Cag6/HP0526) are just required for the translocation of CagA. However, relatively little is known about their functions and structural organization because they exhibit a nondetectable sequence similarity with T4SS components in the current databases. In this review, we conducted an exhaustive analysis of the literature to present the biochemistry, putative role, localization, and interactions of each of these eight additional cag T4SS components. © 2017 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Ahlstedt, Ingela; Lindholm, Catharina; Lönroth, Hans; Hamlet, Annika; Svennerholm, Ann-Mari; Quiding-Järbrink, Marianne
Using immunohistochemical staining, we examined the presence of secretory component (SC) on epithelial cells in gastric and duodenal biopsy specimens collected from Helicobacter pylori-infected individuals and healthy controls. Gastric epithelial cells from healthy volunteers expressed low, but detectable, levels of SC. In contrast, significantly higher level of expression of SC (P < 0.001) was observed on epithelial cells in the antra of H. pylori-infected individuals. The antral SC expression correlated with staining for gamma interferon of intraepithelial and lamina propria lymphocytes (rs = 0.76 and 0.69, respectively, P < 0.001) and correlated weakly with production of tumor necrosis factor alpha (rs = 0.43, P < 0.05), but it did not correlate at all with interleukin-4 production. PMID:10456951
Bazillou, M; Fendri, C; Castel, O; Ingrand, P; Fauchére, J L
Superficial and released components were extracted from six selected Helicobacter pylori strains. The protein and antigenic profiles of these extracts were representative of the profiles found most frequently among the clinical strains and included major peptidic fractions at 19, 23.5, 57, 68, 76, 118, and 132 kDa and major antigens at 68, 57, and 23.5 kDa. Immuno-cross-reactions were seen with a hyperimmune rabbit serum to Campylobacter fetus but not with sera to Campylobacter jejuni or Salmonella spp. An antigenic preparation was obtained by pooling equivalent quantities of each extract, and the antigenic preparation was used to study the antibody responses of sera from 65 French patients and 127 Tunisian patients. By enzyme-linked immunosorbent assay, we observed that the sera from French and Tunisian patients clustered into two populations, defined as antibody positive (72 patients) and antibody negative (120 patients). The antibody-positive patients were more frequently infected with H. pylori (P < 0.01) and were more frequently affected with gastritis (P = 0.05). However, no correlation between antibody levels and clinical signs of dyspepsia was noticed. The proportions of antibody-positive patients were similar in France and Tunisia. Antibody-positive and antibody-negative sera were studied by western blot (immunoblot) analysis. The antibody-positive sera revealed an average of 7.7 antigenic bands, whereas the antibody-negative sera revealed an average of 2.4 antigenic bands (P < 0.01). The antigens between 15 and 40 kDa and greater than 66 kDa were specifically recognized by the antibody-positive sera, although in this molecular size range the antibody profiles of these sera exhibited a fairly high degree of diversity. We conclude that the superficial and released components from H. pylori contain a variety of bacterial immunogens and may be useful in antigenic preparations for the serodiagnosis of H. pylori infections. Moreover, a group of antigens in
Zhang, Jin; Fan, Fei; Zhao, Yanhe; Sun, Lifang; Liu, Yadan; Keegan, Ronan M; Isupov, Michail N; Wu, Yunkun
Helicobacter pylori, a Gram-negative bacterial pathogen prevalent in the human population, is the causative agent of severe gastric diseases. An H. pylori type IV secretion (T4S) system encoded by the cytotoxin-associated gene pathogenicity island (cagPAI) is responsible for communication with host cells. As a component of the cagPAI T4S system core complex, CagX plays an important role in virulence-protein translocation into the host cells. In this work, the crystal structure of the C-terminal domain of CagX (CagXct), which is a homologue of the VirB9 protein from the VirB/D4 T4S system, is presented. CagXct is only the second three-dimensional structure to be elucidated of a VirB9-like protein. Another homologue, TraO, which is encoded on the Escherichia coli conjugative plasmid pKM101, shares only 19% sequence identity with CagXct; however, there is a remarkable similarity in tertiary structure between these two β-sandwich protein domains. Most of the residues that are conserved between CagXct and TraO are located within the protein core and appear to be responsible for the preservation of this domain fold. The studies presented here will contribute to our understanding of different bacterial T4S systems.
Zhang, Jin; Fan, Fei; Zhao, Yanhe; Sun, Lifang; Liu, Yadan; Wu, Yunkun
Helicobacter pylori, a Gram-negative bacterial pathogen prevalent in the human population, is the causative agent of severe gastric diseases. An H. pylori type IV secretion (T4S) system encoded by the cytotoxin-associated gene pathogenicity island (cagPAI) is responsible for communication with host cells. As a component of the cagPAI T4S system core complex, CagX plays an important role in virulence-protein translocation into the host cells. In this work, the crystal structure of the C-terminal domain of CagX (CagXct), which is a homologue of the VirB9 protein from the VirB/D4 T4S system, is presented. CagXct is only the second three-dimensional structure to be elucidated of a VirB9-like protein. Another homologue, TraO, which is encoded on the Escherichia coli conjugative plasmid pKM101, shares only 19% sequence identity with CagXct; however, there is a remarkable similarity in tertiary structure between these two β-sandwich protein domains. Most of the residues that are conserved between CagXct and TraO are located within the protein core and appear to be responsible for the preservation of this domain fold. The studies presented here will contribute to our understanding of different bacterial T4S systems. PMID:28291753
Tan, Ran-Jing; Sun, He-Qiang; Zhang, Wei; Yuan, Han-Mei; Li, Bin; Yan, Hong-Tao; Lan, Chun-Hui; Yang, Jun; Zhao, Zhuo; Wu, Jin-Jin; Wu, Chao
Helicobacter pylori (H. pylori) seem to involve in the etiology of chronic spontaneous urticaria (CSU). But studies of the pathogenic mechanism are very little. In this study, we detected the serum-specific anti-H. pylori IgG and IgE antibodies in 211 CSU and 137 normal subjects by enzyme-linked immunosorbent assay (ELISA), evaluated the direct activation effects of H. pylori preparations and its protein components on human LAD2 mast cell line in vitro, and analyzed the specific protein ingredients and functions of the most effective H. pylori mixed protein component using liquid chromatography-mass spectrometry and ELISA assay. In CSU patients, the positive rate of anti-H. pylori IgG positive rate was significantly higher than that in normal controls, and the anti-H. pylori IgE levels had no statistical difference between H. pylori-infected patients with and without CSU. Further studies suggested that H. pylori preparations can directly activate human LAD2 mast cell line in a dose-dependent manner and its most powerful protein component was a mixture of 21-35 kDa proteins. Moreover, the 21-35 kDa mixed protein component mainly contained 23 kinds of proteins, which can stimulate the release of histamine, TNF-a, IL-3, IFN-γ, and LTB4 by LAD2 cells in a dose-dependent or time-dependent manner. A 21-35 kDa mixed protein component should be regarded as the most promising pathogenic factor contributing to the CSU associated with H. pylori infection. © 2016 John Wiley & Sons Ltd.
Takeuchi, Hiroaki; Trang, Vu Thu; Morimoto, Norihito; Nishida, Yoshie; Matsumura, Yoshihisa; Sugiura, Tetsuro
The bacterial pathogen Helicobacter pylori (H. pylori) colonizes in over half of the world’s population. H. pylori that establishes life-long infection in the stomach is definitely associated with gastro-duodenal diseases and a wide variety of non-gastrointestinal tract conditions such as immune thrombocytopenia. Triple therapy which consists of a proton pump inhibitor and combinations of two antibiotics (amoxicillin, clarithromycin or amoxicillin, metronidazol) is commonly used for H. pylori eradication. Recently, the occurrence of drug-resistant H. pylori and the adverse effect of antibiotics have severely weakened eradication therapy. Generally antibiotics induce the disturbance of human gastrointestinal microflora. Furthermore, there are inappropriate cases of triple therapy such as allergy to antibiotics, severe complications (liver and/or kidney dysfunction), the aged and people who reject the triple therapy. These prompt us to seek alterative agents instead of antibiotics and to develop more effective and safe therapy with these agents. The combination of these agents actually may result in lower a dose of antibiotics. There are many reports world-wide that non-antibiotic substances from natural products potentially have an anti-H. pylori agent. We briefly review the constituents derived from nature that fight against H. pylori in the literature with our studies. PMID:25083070
Determinants on tmRNA for initiating efficient and precise trans-translation: some mutations upstream of the tag-encoding sequence of Escherichia coli tmRNA shift the initiation point of trans-translation in vitro.
Lee, S; Ishii, M; Tadaki, T; Muto, A; Himeno, H
tmRNA facilitates a novel translation, trans-translation, in which a ribosome can switch between translation of a truncated mRNA and the tmRNA's tag sequence. The mechanism underlying resumption of translation at a definite position is not known. In the present study, the effects of mutations around the initiation point of the tag-encoding sequence of Escherichia coli tmRNA on the efficiency and the frame of tag translation were assessed by measuring the incorporations of several amino acids into in vitro poly (U)-dependent tag-peptide synthesis. One-nucleotide insertions within the tag-encoding region did not shift the frame of tag translation. Any 1-nt deletion within the span of -5 to -1, but not at -6, made the frame of tag translation heterologous. Positions at which a single base substitution caused a decrease of trans-translation efficiency were concentrated within the span of -4 to -2. In particular, an A-4 to C-4 mutation seriously damaged the trans-translation, although this mutant retained normal aminoacylation and ribosome-binding abilities. A possible stem and loop structure around this region was not required for transtranslation. It was concluded that the tag translation requires the primary sequence encompassing -6 to +11, in which the central 3 nt, A-4, G-3, and U-2, play an essential role. It was also found that several base substitutions within the span of -6 to -1 extensively shifted the tag-initiation point by -1. PMID:11453072
Gopal, Gopal Jee; Kumar, Awanish; Pal, Jagannath; Mukhopadhyay, Gauranga
Gram-negative bacteria Helicobacter pylori cause gastric ulcer, duodenal cancer, and found in almost half of the world’s residents. The protein responsible for this disease is secreted through type IV secretion system (TFSS) of H. pylori. TFSS is encoded by 40-kb region of chromosomal DNA known as cag-pathogenicity island (PAI). TFSS comprises of three major components: cytoplasmic/inner membrane ATPase, transmembrane core-complex and outer membranous pilli, and associated subunits. Core complex consists of CagX, CagT, CagM, and Cag3(δ) proteins as per existing knowledge. In this study, we have characterized one of the important component of core-complex forming sub-unit protein, i.e., CagX. Complete ORF of CagX except signal peptide coding region was cloned and expressed in pET28a vector. Purification of CagX protein was performed, and polyclonal anti-sera against full-length recombinant CagX were raised in rabbit model. We obtained a very specific and high titer, CagX anti-sera that were utilized to characterize endogenous CagX. Surface localization of CagX was also seen by immunofluorescence microscopy. In short for the first time a full-length CagX was characterized, and we showed that CagX is the part of high molecular weight core complex, which is important for assembly and function of H. pylori TFSS. PMID:24637488
Kumar, Sathish; Kolodkin-Gal, Ilana; Vesper, Oliver; Alam, Nawsad; Schueler-Furman, Ora; Moll, Isabella; Engelberg-Kulka, Hanna
Eshcerichia coli mazEF is a stress-induced toxin-antitoxin module mediating cell death and requiring a quorum-sensing (QS) extracellular death factor (EDF), the pentapeptide NNWNN. Here we uncovered several distinct molecular mechanisms involved in its generation from the zwf mRNA encoding glucose-6-phosphate dehydrogenase. In particular, we show that, under stress conditions, the endoribonuclease MazF cleaves specific ACA sites, thereby generating a leaderless zwf mRNA which is truncated 30 codons after the EDF-encoding region. Since the nascent ribosome peptide exit tunnel can accommodate up to 40 amino acids, this arrangement allows the localization of the EDF residues inside the tunnel when the ribosome is stalled at the truncation site. Moreover, ribosome stalling activates the trans-translation system, which provides a means for the involvement of ClpPX in EDF generation. Furthermore, the trans-translation is described as a regulatory system that attenuated the generation of EDF, leading to low levels of EDF in the single cell. Therefore, the threshold EDF molecule concentration required is achieved only by the whole population, as expected for QS. Bacteria communicate with one another via quorum-sensing (QS) signal molecules. QS provides a mechanism for bacteria to monitor each other's presence and to modulate gene expression in response to population density. Previously, we added E. coli pentapeptide EDF to this list of QS molecules. We showed that, under stress conditions, the induced MazF, an endoribonuclease cleaving at ACA sites, generates EDF from zwf. Here we studied the mechanism of EDF generation and asked whether it is related to EDF density dependency. We illustrated that, under stress conditions, multiple distinct complex mechanisms are involved in EDF generation. This includes formation of leaderless truncated zwf mRNA by MazF, configuration of a length corresponding to the nascent ribosome peptide exit tunnel, rescue performed by the trans-translation
Kumar, Sathish; Kolodkin-Gal, Ilana; Vesper, Oliver; Alam, Nawsad; Schueler-Furman, Ora; Moll, Isabella
ABSTRACT Eshcerichia coli mazEF is a stress-induced toxin-antitoxin module mediating cell death and requiring a quorum-sensing (QS) extracellular death factor (EDF), the pentapeptide NNWNN. Here we uncovered several distinct molecular mechanisms involved in its generation from the zwf mRNA encoding glucose-6-phosphate dehydrogenase. In particular, we show that, under stress conditions, the endoribonuclease MazF cleaves specific ACA sites, thereby generating a leaderless zwf mRNA which is truncated 30 codons after the EDF-encoding region. Since the nascent ribosome peptide exit tunnel can accommodate up to 40 amino acids, this arrangement allows the localization of the EDF residues inside the tunnel when the ribosome is stalled at the truncation site. Moreover, ribosome stalling activates the trans-translation system, which provides a means for the involvement of ClpPX in EDF generation. Furthermore, the trans-translation is described as a regulatory system that attenuated the generation of EDF, leading to low levels of EDF in the single cell. Therefore, the threshold EDF molecule concentration required is achieved only by the whole population, as expected for QS. PMID:26814184
Nonin-Lecomte, Sylvie; Felden, Brice; Dardel, Frédéric
The transfer-messenger RNA (tmRNA) pseudoknot PK1 is essential for bacterial trans-translation, a ribosomal rescue mechanism. We report the solution structure of PK1 from Aquifex aeolicus, which despite an unprecedented small number of nucleotides and thus an unprecented compact size, displays a very high thermal stability. Several unusual structural features account for these properties and indicate that PK1 belongs to the class of ribosomal frameshift pseudoknots. This suggests a similarity between the mechanism of programmed ribosomal frameshifting and trans-translation.
Zhu, Yingdong; Zhang, Ping; Yu, Haiping; Li, Jia; Wang, Ming-Wei; Zhao, Weimin
Chemical studies on the constituents of Dracaena cochinchinensis led to the discovery of eight new flavonoid derivatives ( 1- 8) along with 14 known compounds ( 9- 22). The identification and structural elucidation of these isolates were based on spectral analyses. All isolates were tested for antibacterial activities against Helicobacter pylori (ATCC43504) and thrombin inhibitory effects. As a result, new flavonoid derivatives 6 and 7 and (2 S)-4',7-dihydroxy-8-methylflavan ( 11) were found to be most efficacious against H. pylori (ATCC43504) with MIC values of 29.5, 29.5, and 31.3 microM, respectively, and the seven new flavonoid derivatives ( 1- 7) and one known biflavonoid ( 9) were observed to exhibit moderate thrombin inhibitory activity.
Fan, Yi; Dai, Yazhuang; Hou, Meijing; Wang, Huilin; Yao, Hongwei; Guo, Chenyun; Lin, Donghai; Liao, Xinli
Ribosomal protein S1 (RpsA), the largest 30S protein in ribosome, plays a significant role in translation and trans-translation. In Mycobacterium tuberculosis, the C-terminus of RpsA is known as tuberculosis drug target of pyrazinoic acid, which inhibits the interaction between MtRpsA and tmRNA in trans-translation. However, the molecular mechanism underlying the interaction of MtRpsA with tmRNA remains unknown. We herein analyzed the interaction of the C-terminal domain of MtRpsA with three RNA fragments poly(A), sMLD and pre-sMLD. NMR titration analysis revealed that the RNA binding sites on MtRpsA(CTD) are mainly located in the β2, β3 and β5 strands and the adjacent L3 loop of the S1 domain. Fluorescence experiments determined the MtRpsA(CTD) binding to RNAs are in the micromolar affinity range. Sequence analysis also revealed conserved residues in the mapped RNA binding region. Residues L304, V305, G308, F310, H322, I323, R357 and I358 were verified to be the key residues influencing the interaction between MtRpsA(CTD) and pre-sMLD. Molecular docking further confirmed that the poly(A)-like sequence and sMLD of tmRNA are all involved in the protein-RNA interaction, through charged interaction and hydrogen bonds. The results will be beneficial for designing new anti-tuberculosis drugs. Copyright © 2017 Elsevier Inc. All rights reserved.
Marcus, Elizabeth A.; Sachs, George; Wen, Yi; Scott, David R.
Background The pH sensitive Helicobacter pylori ArsRS two-component system (TCS) aids survival of this neutralophile in the gastric environment by directly sensing and responding to environmental acidity. ArsS is required for acid-induced trafficking of urease and its accessory proteins to the inner membrane, allowing rapid, urea-dependent cytoplasmic and periplasmic buffering. Expression of ArsR, but not its phosphorylation, is essential for bacterial viability. The aim of this study is to characterize the roles of ArsS and ArsR in the response of H. pylori to acid. Materials and Methods Wildtype H. pylori and an arsR(D52N) phosphorylation deficient strain were incubated at acidic or neutral pH. Gene and protein expression, survival, membrane trafficking of urease proteins, urease activity, and internal pH were studied. Results Phosphorylation of ArsR is not required for acid survival. ArsS-driven trafficking of urease proteins to the membrane in acid, required for recovery of internal pH, is independent of ArsR phosphorylation. ArsR phosphorylation increases expression of the urease gene cluster, and the loss of negative feedback in a phosphorylation deficient mutant leads to an increase in total urease activity. Conclusions ArsRS has a dual function in acid acclimation: regulation of urease trafficking to UreI at the cytoplasmic membrane, driven by ArsS, and regulation of urease gene cluster expression, driven by phosphorylation of ArsR. ArsS and ArsR work through phosphorylation dependent and independent regulatory mechanisms to impact acid acclimation and allow gastric colonization. Furthering understanding of the intricacies of acid acclimation will impact the future development of targeted, non-antibiotic treatment regimens. PMID:25997502
Loh, John T; Gupta, Shobhana S; Friedman, David B; Krezel, Andrzej M; Cover, Timothy L
Previous studies have shown that the Helicobacter pylori ArsRS two-component signal transduction system contributes to acid-responsive gene expression. To identify additional members of the ArsRS regulon and further investigate the regulatory role of the ArsRS system, we analyzed protein expression in wild-type and arsS null mutant strains. Numerous proteins were differentially expressed in an arsS mutant strain compared to a wild-type strain when the bacteria were cultured at pH 5.0 and also when they were cultured at pH 7.0. Genes encoding 14 of these proteins were directly regulated by the ArsRS system, based on observed binding of ArsR to the relevant promoter regions. The ArsRS-regulated proteins identified in this study contribute to acid resistance (urease and amidase), acetone metabolism (acetone carboxylase), resistance to oxidative stress (thioredoxin reductase), quorum sensing (Pfs), and several other functions. These results provide further definition of the ArsRS regulon and underscore the importance of the ArsRS system in regulating expression of H. pylori proteins during bacterial growth at both neutral pH and acidic pH.
... illnesses. H. pylori , which used to be called Campylobacter pylori , also can cause peptic ulcers (commonly known ... H. Pylori Antigen Food Safety for Your Family Campylobacter Infections Pyloric Stenosis Peptic Ulcers Digestive System Vomiting ...
Marcus, Elizabeth A; Sachs, George; Wen, Yi; Scott, David R
The pH-sensitive Helicobacter pylori ArsRS two-component system (TCS) aids survival of this neutralophile in the gastric environment by directly sensing and responding to environmental acidity. ArsS is required for acid-induced trafficking of urease and its accessory proteins to the inner membrane, allowing rapid, urea-dependent cytoplasmic and periplasmic buffering. Expression of ArsR, but not its phosphorylation, is essential for bacterial viability. The aim of this study was to characterize the roles of ArsS and ArsR in the response of H. pylori to acid. Wild-type H. pylori and an arsR(D52N) phosphorylation-deficient strain were incubated at acidic or neutral pH. Gene and protein expression, survival, membrane trafficking of urease proteins, urease activity, and internal pH were studied. Phosphorylation of ArsR is not required for acid survival. ArsS-driven trafficking of urease proteins to the membrane in acid, required for recovery of internal pH, is independent of ArsR phosphorylation. ArsR phosphorylation increases expression of the urease gene cluster, and the loss of negative feedback in a phosphorylation-deficient mutant leads to an increase in total urease activity. ArsRS has a dual function in acid acclimation: regulation of urease trafficking to UreI at the cytoplasmic membrane, driven by ArsS, and regulation of urease gene cluster expression, driven by phosphorylation of ArsR. ArsS and ArsR work through phosphorylation-dependent and phosphorylation-independent regulatory mechanisms to impact acid acclimation and allow gastric colonization. Furthering understanding of the intricacies of acid acclimation will impact the future development of targeted, nonantibiotic treatment regimens. © 2015 John Wiley & Sons Ltd.
Dunn, B E; Cohen, H; Blaser, M J
Helicobacter pylori is a gram-negative bacterium which causes chronic gastritis and plays important roles in peptic ulcer disease, gastric carcinoma, and gastric lymphoma. H. pylori has been found in the stomachs of humans in all parts of the world. In developing countries, 70 to 90% of the population carries H. pylori. In developed countries, the prevalence of infection is lower. There appears to be no substantial reservoir of H. pylori aside from the human stomach. Transmission can occur by iatrogenic, fecal-oral, and oral-oral routes. H. pylori is able to colonize and persist in a unique biological niche within the gastric lumen. All fresh isolates of H. pylori express significant urease activity, which appears essential to the survival and pathogenesis of the bacterium. A variety of tests to diagnose H. pylori infection are now available. Histological examination of gastric tissue, culture, rapid urease testing, DNA probes, and PCR analysis, when used to test gastric tissue, all require endoscopy. In contrast, breath tests, serology, gastric juice PCR, and urinary excretion of [15N]ammonia are noninvasive tests that do not require endoscopy. In this review, we highlight advances in the detection of the presence of the organism and methods of differentiating among types of H. pylori, and we provide a background for appropriate chemotherapy of the infection. PMID:9336670
Helicobacter pylori is a pathogenic bacteria which inhabits the human stomach and upper gastrointestinal tract. This encyclopedic entry summarizes the potential role of this organism as a waterborne pathogen. Information is provided on the physiology and morphology of this bacter...
Helicobacter pylori is a pathogenic bacteria which inhabits the human stomach and upper gastrointestinal tract. This encyclopedic entry summarizes the potential role of this organism as a waterborne pathogen. Information is provided on the physiology and morphology of this bacter...
Background and aim We present a new clinical entity in relation to the Helicobacter pylori infection characterized by complex and varied clinical extra-digestive manifestations. Clinical findings such as asthenia, adynamia, sleep disorders, hair and nails modifications, digestive symptoms and heart rhythm disorders describe the clinical aspect of toxicosis associated with Helicobacter pylori infection. Methods The clinical presentation and therapy of patients with Helicobacter pylori infection were analyzed. Results Combined drug therapy: antibiotics + proton pump inhibitors + colloidal bismuth compound determinate remission of the symptoms in the first 3 to 5 days. The characteristic of the relation between Helicobacter pylori and the mucus-epithelial cell complex, the properties of the bacterial cell components, and the inflammatory and immunological response targeting other organs describe the immuno-pathological outbreak of Helicobacter pylori. Conclusion We support the term of toxicosis associated with Helicobacter pylori infection in selected cases. PMID:26527950
... urease test (RUT) for H. pylori Formal name: Helicobacter pylori Related tests: Gastrin At a Glance Test ... else I should know? How is it used? Helicobacter pylori testing is used to diagnose an infection ...
... Issues Listen Español Text Size Email Print Share Helicobacter Pylori Infections Page Content Article Body Most people, ... always) caused by bacteria—specifically, an organism called Helicobacter pylori. H pylori infections occur at a low ...
Ahn, Hyo Jun; Lee, Dong Soo
Gastric cancer still is a major concern as the third most common cancer worldwide, despite declining rates of incidence in many Western countries. Helicobacter pylori (H. pylori) is the major cause of gastric carcinogenesis, and its infection insults gastric mucosa leading to the occurrence of atrophic gastritis which progress to intestinal metaplasia, dysplasia, early gastric cancer, and advanced gastric cancer consequently. This review focuses on multiple factors including microbial virulence factors, host genetic factors, and environmental factors, which can heighten the chance of occurrence of gastric adenocarcinoma due to H. pylori infection. Bacterial virulence factors are key components in controlling the immune response associated with the induction of carcinogenesis, and cagA and vacA are the most well-known pathogenic factors. Host genetic polymorphisms contribute to regulating the inflammatory response to H. pylori and will become increasingly important with advancing techniques. Environmental factors such as high salt and smoking may also play a role in gastric carcinogenesis. It is important to understand the virulence factors, host genetic factors, and environmental factors interacting in the multistep process of gastric carcinogenesis. To conclude, prevention via H. pylori eradication and controlling environmental factors such as diet, smoking, and alcohol is an important strategy to avoid H. pylori-associated gastric carcinogenesis. PMID:26690981
Pflock, Michael; Kennard, Simone; Delany, Isabel; Scarlato, Vincenzo; Beier, Dagmar
The nickel-containing enzyme urease is an essential colonization factor of the human gastric pathogen Helicobacter pylori which enables the bacteria to survive the low-pH conditions of the stomach. Transcription of the urease genes is positively controlled in response to increasing concentrations of nickel ions and acidic pH. Here we demonstrate that acid-induced transcription of the urease genes is mediated directly by the ArsRS two-component system. Footprint analyses identify binding sites of the phosphorylated ArsR response regulator within the ureA and ureI promoters. Furthermore, deletion of a distal upstream ArsR binding site of the ureA promoter demonstrates its role in acid-dependent activation of the promoter. In addition, acid-induced transcription of the ureA gene is unaltered in a nikR mutant, providing evidence that pH-responsive regulation and nickel-responsive regulation of the ureA promoter are mediated by independent mechanisms involving the ArsR response regulator and the NikR protein. PMID:16177315
Wroblewski, Lydia E; Peek, Richard M
Gastric adenocarcinoma is one of the leading causes of cancer-related death worldwide and Helicobacter pylori infection is the strongest known risk factor for this disease. Although the stomach was once thought to be a sterile environment, it is now known to house many bacterial species leading to a complex interplay between H. pylori and other residents of the gastric microbiota. In addition to the role of H. pylori virulence factors, host genetic polymorphisms, and diet, it is now becoming clear that components of the gastrointestinal microbiota may also influence H. pylori-induced pathogenesis. In this chapter, we discuss emerging data regarding the gastric microbiota in humans and animal models and alterations that occur to the composition of the gastric microbiota in the presence of H. pylori infection that may augment the risk of developing gastric cancer.
Chmiela, Magdalena; Gonciarz, Weronika
Gram-negative bacteria Helicobacter pylori (H. pylori) colonize gastric mucosa in humans and increase the risk of serious diseases such as gastric and duodenal ulcers, stomach cancers and mucosa associated lymphoid tissue lymphoma. The role of H. pylori infection in the pathogenesis of several extragastric diseases has been suggested including immune thrombocytopenic purpura, iron deficiency anemia, vitamin D deficiency, cardiovascular diseases, diabetes mellitus and dermatological disorders. Also neurological diseases and even lung cancer have attracted researchers concern. The relation between H. pylori infection and a growth retardation in children has also been suggested. Many mechanisms of molecular mimicry between H. pylori and the host have been proposed as a pathogen strategy to manipulate the immune system of the host in order to remain unrecognized and avoid eradication. A lot of effort has been put into the demonstration of homologous sequences between H. pylori and host compounds. However, knowledge about how often autoantibodies or autoreactive T lymphocytes induced during H. pylori infections cause pathological disorders is insufficient. This review provides data on H. pylori antigenic mimicry and possible deleterious effects due to the induction of immune response to the components common to these bacteria and the host.
Chmiela, Magdalena; Gonciarz, Weronika
Gram-negative bacteria Helicobacter pylori (H. pylori) colonize gastric mucosa in humans and increase the risk of serious diseases such as gastric and duodenal ulcers, stomach cancers and mucosa associated lymphoid tissue lymphoma. The role of H. pylori infection in the pathogenesis of several extragastric diseases has been suggested including immune thrombocytopenic purpura, iron deficiency anemia, vitamin D deficiency, cardiovascular diseases, diabetes mellitus and dermatological disorders. Also neurological diseases and even lung cancer have attracted researchers concern. The relation between H. pylori infection and a growth retardation in children has also been suggested. Many mechanisms of molecular mimicry between H. pylori and the host have been proposed as a pathogen strategy to manipulate the immune system of the host in order to remain unrecognized and avoid eradication. A lot of effort has been put into the demonstration of homologous sequences between H. pylori and host compounds. However, knowledge about how often autoantibodies or autoreactive T lymphocytes induced during H. pylori infections cause pathological disorders is insufficient. This review provides data on H. pylori antigenic mimicry and possible deleterious effects due to the induction of immune response to the components common to these bacteria and the host. PMID:28652651
Wen, Yi; Feng, Jing; Scott, David R; Marcus, Elizabeth A; Sachs, George
About 200 genes of the gastric pathogen Helicobacter pylori increase expression at medium pHs of 6.2, 5.5, and 4.5, an increase that is abolished or much reduced by the buffering action of urease. Genes up-regulated by a low pH include the two-component system HP0165-HP0166, suggesting a role in the regulation of some of the pH-sensitive genes. To identify targets of HP0165-HP0166, the promoter regions of genes up-regulated by a low pH were grouped based on sequence similarity. Probes for promoter sequences representing each group were subjected to electrophoretic mobility shift assays (EMSA) with recombinant HP0166-His(6) or a mutated response regulator, HP0166-D52N-His(6), that can specifically determine the role of phosphorylation of HP0166 in binding (including a control EMSA with in-vitro-phosphorylated HP0166-His(6)). Nineteen of 45 promoter-regulatory regions were found to interact with HP0166-His(6). Seven promoters for genes encoding alpha-carbonic anhydrase, omp11, fecD, lpp20, hypA, and two with unknown function (pHP1397-1396 and pHP0654-0675) were clustered in gene group A, which may respond to changes in the periplasmic pH at a constant cytoplasmic pH and showed phosphorylation-dependent binding in EMSA with HP0166-D52N-His(6). Twelve promoters were clustered in groups B and C whose up-regulation likely also depends on a reduction of the cytoplasmic pH at a medium pH of 5.5 or 4.5. Most of the target promoters in groups B and C showed phosphorylation-dependent binding with HP0166-D52N-His(6), but promoters for ompR (pHP0166-0162), pHP0682-0681, and pHP1288-1289 showed phosphorylation-independent binding. These findings, combined with DNase I footprinting, suggest that HP0165-0166 is an acid-responsive signaling system affecting the expression of pH-sensitive genes. Regulation of these genes responds either to a decrease in the periplasmic pH alone (HP0165 dependent) or also to a decrease in the cytoplasmic pH (HP0165 independent).
Vitale, G; Barbaro, F; Ianiro, G; Cesario, V; Gasbarrini, G; Franceschi, F; Gasbarrini, A
H. pylori is a gram-negative pathogen, etiologically associated with atrophic and non-atrophic gastritis, peptic ulcer, primary gastric B-cell lymphoma and gastric carcinoma. Several observations demonstrated a correlation between H. pylori and malabsorption of essential nutrients; epidemiological studies have shown an association between H. pylori infection and iron deficiency anemia, while the absorption of some vitamins such as vitamin B12, vitamin A, vitamin C, folic acid and Vitamin E may be affected by the infection. The main mechanism related to malabsorption of this components is the modified intragastric pH (hypo- achlorhydria) due to H. pylori infection. Moreover H. pylori is also able to determine a modification of gastrointestinal hormones by reducing plasma levels of ghrelin and increasing those of leptin and gastrin, thus affecting appetite and promoting the occurrence of dyspeptic symptoms. On the other hand, H. pylori eradication has been shown to improve serum level of iron and vitamin B12, has some effects on Vitamin A and Vitamin E absorption and has a late effects on ghrelin levels. As a consequence of those effects, H. pylori is also associated with childhood malnutrition in developing countries either for the occurrence of malabsorption or for an increased susceptibility to enteric infections caused by hypochlorhydria.
Helicobacter pylori (H. pylori) is a type of bacteria that causes infection in the stomach. It is found in about two-thirds of ... or stool to see if it contains H. pylori. The best treatment is a combination of antibiotics ...
Murakami, Kazunari; Sakurai, Yuuichi; Shiino, Madoka; Funao, Nobuo; Nishimura, Akira; Asaka, Masahiro
Objective The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy. Design A randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20 mg to lansoprazole 30 mg as part of first-line triple therapy (with amoxicillin 750 mg and clarithromycin 200 or 400 mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second-line vonoprazan-based triple therapy (with amoxicillin 750 mg and metronidazole 250 mg) as an open-label treatment. Results Of the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects completed first-line therapy and 50 subjects completed second-line therapy. The first-line eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being 16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of vonoprazan (p<0.0001). The second-line eradication rate (secondary end point) was also high (98.0%; 95% CI 89.4% to 99.9%) in those who received second-line therapy (n=50). Both first-line triple therapies were well tolerated with no notable differences. Second-line triple therapy was also well tolerated. Conclusion Vonoprazan is effective as part of first-line triple therapy and as part of second-line triple therapy in H pylori-positive patients with a history of gastric or duodenal ulcer. Trial registration number NCT01505127. PMID:26935876
... Your 1- to 2-Year-Old Stool Test: H. Pylori Antigen KidsHealth > For Parents > Stool Test: H. Pylori Antigen A A A What's in this article? ... en español Muestra de materia fecal: antígeno de H. pylori What It Is Helicobacter pylori ( H. pylori ) bacteria ...
Hasni, Sarfaraz Ahmed
Purpose of review The etiology of most autoimmune diseases remains elusive. Prevailing evidence suggests an environmental trigger in a genetically susceptible individual. Helicobacter pylori (H. pylori) have managed to survive in a hostile environment in its host for long period and have evaded eradication by immune system. Its chronic interaction with the immune system and the ubiquitous presence worldwide makes H. pylori an ideal candidate to study as a trigger of autoimmune phenomena. In this review, we would present data regarding the interplay between H. pylori and various components of the immune system and its association with various autoimmune diseases. Recent findings Strong associations of H. pylori with some autoimmune diseases such as immune thrombocytopenia have been found; but most other autoimmune disease studies have revealed conflicting data. The chronic survival of H. pylori in humans is possible because of an overall downregulation of the body’s immune response. In addition to this overall effect on the immune system, there are clinical and epidemiological data suggestive of H. pylori infection having a protective role in some autoimmune diseases. Summary Based on our review H. pylori status should be checked and treated only in certain autoimmune diseases such as ITP. For majority of the autoimmune diseases role of H. pylori remains controversial signifying need for further research. PMID:22617822
Camilo, Vania; Sugiyama, Toshiro; Touati, Eliette
Helicobacter pylori is responsible for the most commonly found infection in the world's population. It is the major risk factor for gastric cancer development. Numerous studies published over the last year provide new insights into the strategies employed by H. pylori to adapt to the extreme acidic conditions of the gastric environment, to establish persistent infection and to deregulate host functions, leading to gastric pathogenesis and cancer. In this review, we report recent data on the mechanisms involved in chemotaxis, on the essential role of nickel in acid resistance and gastric colonization, on the importance of adhesins and Hop proteins and on the role of CagPAI-components and CagA. Among the host functions, a special focus has been made on the escape from immune response, the ability of bacteria to induce genetic instability and modulate telomeres, the mechanism of autophagy and the deregulation of micro RNAs. © 2017 John Wiley & Sons Ltd.
Wex, Thomas; Kuester, Doerthe; Mönkemüller, Klaus; Stahr, Antje; Fry, Lucia C; Kandulski, Arne; Kropf, Siegfried; Roessner, Albert; Malfertheiner, Peter
Gastroesophageal reflux disease is associated with impaired epithelial barrier function and abnormal expression of proteins forming cell-cell contacts by tight junctions and desmosomes in distal esophageal squamous mucosa. Although gastroesophageal reflux disease and Helicobacter pylori are both associated with chronic inflammation of the adjacent cardia mucosa, it is not known whether these lead to derangements of the desmosomal complexes. Here, we assessed the expression of 4 proteins (plakoglobin and desmoglein 1, 2, and 3) forming epithelial desmosomal complexes by quantitative reverse transcription polymerase chain reaction and immunohistochemistry in biopsies from 67 patients with gastroesophageal reflux disease and 23 gastroesophageal reflux disease-negative controls. Plakoglobin and desmoglein 2 were ubiquitously expressed in all samples, whereas desmoglein 1 and 3 were not expressed in cardia mucosa. Gastroesophageal reflux disease was specifically associated with elevated transcript levels of desmoglein 2 and plakoglobin. These were significantly increased from 2.0- to 2.7-fold in patients with gastroesophageal reflux disease compared with controls (P < .01), and significantly increased immunohistochemical scores for both proteins were observed (P < .05) as well. The combined presence of gastroesophageal reflux disease and Helicobacter pylori infection had no additional effect on desmosomal gene expression. Taken together, the up-regulation of plakoglobin and desmoglein 2 in cardia mucosa of patients with gastroesophageal reflux disease supports the concept that the "transition zone" between distal esophagus and proximal stomach is affected by gastroesophageal reflux disease as well, and architectural and molecular changes in the desmosomal compartment contribute to the pathogenesis of gastroesophageal reflux disease in the cardia mucosa.
Murakami, Kazunari; Sakurai, Yuuichi; Shiino, Madoka; Funao, Nobuo; Nishimura, Akira; Asaka, Masahiro
The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy. A randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20 mg to lansoprazole 30 mg as part of first-line triple therapy (with amoxicillin 750 mg and clarithromycin 200 or 400 mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second-line vonoprazan-based triple therapy (with amoxicillin 750 mg and metronidazole 250 mg) as an open-label treatment. Of the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects completed first-line therapy and 50 subjects completed second-line therapy. The first-line eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being 16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of vonoprazan (p<0.0001). The second-line eradication rate (secondary end point) was also high (98.0%; 95% CI 89.4% to 99.9%) in those who received second-line therapy (n=50). Both first-line triple therapies were well tolerated with no notable differences. Second-line triple therapy was also well tolerated. Vonoprazan is effective as part of first-line triple therapy and as part of second-line triple therapy in H pylori-positive patients with a history of gastric or duodenal ulcer. NCT01505127. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Pacifico, Lucia; Osborn, John Frederick; Bonci, Enea; Romaggioli, Sara; Baldini, Rossella; Chiesa, Claudio
The combination of a proton pump inhibitor and two antibiotics (clarithromycin plus amoxicillin or metronidazole) has been the recommended first-line therapy since the first guidelines for Helicobacter pylori (H. pylori) infection in children were published. In recent years, the success of eradication therapies has declined, in part due to the development of H. pylori resistant strains. Alternative anti-H. pylori treatments are currently becoming more popular than the traditional eradication methods. Components that may be used either as a monotherapy or, in combination with antimicrobials, resulting in a more effective anti-H. pylori therapy have been investigated in depth by several researchers. One of the potential therapies is probiotic cultures; promising results have been observed in initial studies with numerous probiotic strains. Nevertheless, many questions remain unanswered. In this article, we comprehensively review the possible mechanisms of action of probiotics on H. pylori infection, and present the results of published studies using probiotics as possible agents to control H. pylori infection in children. The effect of the addition of probiotics to the standard H. pylori eradication therapy for the prevention of antibiotic associated side-effects is also discussed. PMID:24574741
Pacifico, Lucia; Osborn, John Frederick; Bonci, Enea; Romaggioli, Sara; Baldini, Rossella; Chiesa, Claudio
The combination of a proton pump inhibitor and two antibiotics (clarithromycin plus amoxicillin or metronidazole) has been the recommended first-line therapy since the first guidelines for Helicobacter pylori (H. pylori) infection in children were published. In recent years, the success of eradication therapies has declined, in part due to the development of H. pylori resistant strains. Alternative anti-H. pylori treatments are currently becoming more popular than the traditional eradication methods. Components that may be used either as a monotherapy or, in combination with antimicrobials, resulting in a more effective anti-H. pylori therapy have been investigated in depth by several researchers. One of the potential therapies is probiotic cultures; promising results have been observed in initial studies with numerous probiotic strains. Nevertheless, many questions remain unanswered. In this article, we comprehensively review the possible mechanisms of action of probiotics on H. pylori infection, and present the results of published studies using probiotics as possible agents to control H. pylori infection in children. The effect of the addition of probiotics to the standard H. pylori eradication therapy for the prevention of antibiotic associated side-effects is also discussed.
Gutiérrez-Escobar, Andrés Julián; Trujillo, Esperanza; Acevedo, Orlando; Bravo, María Mercedes
During the Spanish colonisation of South America, African slaves and Europeans arrived in the continent with their corresponding load of pathogens, including Helicobacter pylori. Colombian strains have been clustered with the hpEurope population and with the hspWestAfrica subpopulation in multilocus sequence typing (MLST) studies. However, ancestry studies have revealed the presence of population components specific to H. pylori in Colombia. The aim of this study was to perform a thorough phylogenomic analysis to describe the evolution of the Colombian urban H. pylori isolates. A total of 115 genomes of H. pylori were sequenced with Illumina technology from H. pylori isolates obtained in Colombia in a region of high risk for gastric cancer. The genomes were assembled, annotated and underwent phylogenomic analysis with 36 reference strains. Additionally, population differentiation analyses were performed for two bacterial genes. The phylogenetic tree revealed clustering of the Colombian strains with hspWestAfrica and hpEurope, along with three clades formed exclusively by Colombian strains, suggesting the presence of independent evolutionary lines for Colombia. Additionally, the nucleotide diversity of horB and vacA genes from Colombian isolates was lower than in the reference strains and showed a significant genetic differentiation supporting the hypothesis of independent clades with recent evolution. The presence of specific lineages suggest the existence of an hspColombia subtype that emerged from a small and relatively isolated ancestral population that accompanied crossbreeding of human population in Colombia.
Polk, D. Brent; Peek, Richard M.
Helicobacter pylori is the dominant species of the human gastric microbiome, and colonization causes a persistent inflammatory response. H. pylori-induced gastritis is the strongest singular risk factor for cancers of the stomach; however, only a small proportion of infected individuals develop malignancy. Carcinogenic risk is modified by strain-specific bacterial components, host responses and/or specific host–microbe interactions. Delineation of bacterial and host mediators that augment gastric cancer risk has profound ramifications for both physicians and biomedical researchers as such findings will not only focus the prevention approaches that target H. pylori-infected human populations at increased risk for stomach cancer but will also provide mechanistic insights into inflammatory carcinomas that develop beyond the gastric niche. PMID:20495574
Polk, D Brent; Peek, Richard M
Helicobacter pylori is the dominant species of the human gastric microbiome, and colonization causes a persistent inflammatory response. H. pylori-induced gastritis is the strongest singular risk factor for cancers of the stomach; however, only a small proportion of infected individuals develop malignancy. Carcinogenic risk is modified by strain-specific bacterial components, host responses and/or specific host-microbe interactions. Delineation of bacterial and host mediators that augment gastric cancer risk has profound ramifications for both physicians and biomedical researchers as such findings will not only focus the prevention approaches that target H. pylori-infected human populations at increased risk for stomach cancer but will also provide mechanistic insights into inflammatory carcinomas that develop beyond the gastric niche.
Zheng, Po-Xing; Fang, Hsin-Yi; Yang, Hsiao-Bai; Tien, Nai-Yueh; Wang, Ming-Cheng; Wu, Jiunn-Jong
Helicobacter pylori is a human gastric pathogen. Antibiotic resistance of H. pylori has become a problem increasing the failure of H. pylori eradication. Therefore alternative approaches are required. The aim of this study was to evaluate the anti-H. pylori activity of Lactobacillus pentosus strain LPS16 and the mechanism of its killing effect. The anti-H. pylori activity of LPS16 was determined by the disc diffusion test and time killing assay. High-performance liquid chromatography analysis was used to analyze the secreted compounds of LPS16. Sixty H. pylori strains isolated from different gastric diseases, having different antibiotic susceptibility were collected to analyze the spectrum of anti-H. pylori activity of LPS16. Adhesion ability of LPS16 to gastric epithelial cell lines was assayed by flow cytometry. The anti-H. pylori activity of LPS16 depended on the secreted component, and lactic acid mediated bactericidal activity against H. pylori. The bactericidal activity did not vary significantly among the strains isolated from different diseases having different antibiotic susceptibility. Moreover, LPS16 can adhere on gastric epithelial cell lines AKG and MKN45. L. pentosus strain LPS16 had the broad-spectrum anti-H. pylori activity, suggesting that it can be used to prevent H. pylori infection. Copyright © 2014. Published by Elsevier B.V.
Newton, M; Bryan, R; Burnham, W R; Kamm, M A
BACKGROUND: One of the major pathophysiological abnormalities in patients with gastro-oesophageal reflux disease is thought to involve transient lower oesophageal sphincter (LOS) relaxations. One component of the neural mechanism controlling the LOS appears to be a reflex are whose afferent limb originates in the gastric fundus. As inflammation is known to be associated with neural activation an investigation was made to determine whether gastric infection with H pylori is altered in prevalence or distribution in patients with reflux disease. METHODS: Five groups of subjects referred for endoscopy-group 1: 25 controls (asymptomatic individuals with anaemia and normal endoscopy); group 2: 36 subjects with erosive oesophagitis alone (Savary-Millar grades I-III); group 3: 16 subjects with duodenal ulcer alone; group 4: 15 subjects with oesophagitis with duodenal ulcer; group 5: 16 subjects with Barrett's oesophagus. No patients were receiving acid suppressants or antibiotics. An antral biopsy specimen was taken for a rapid urease test, and two biopsy specimens were taken from the antrum, fundus, and oesophagus (inflamed and non-inflamed) for histological evidence of inflammation and presence of H pylori using a Giemsa stain. RESULTS: Nine (36%) controls had H pylori. Patients with duodenal ulcer alone had a significantly higher incidence of colonisation by H pylori than other groups (duodenal ulcer 15 (94%); oesophagitis 13 (36%); oesophagitis+duodenal ulcer 6 (40%); Barrett's oesophagus 4 (25%)). H pylori was not more common in oesophagitis. When H pylori colonised the gastric antrum it was usually found in the gastric fundus. There was no difference in anatomical distribution of H pylori in the different patient groups. In Barrett's oesophagus H pylori was found in two of 16 in the metaplastic epithelium. CONCLUSION: H pylori is not more common and its distribution does not differ in those with oesophagitis compared with control subjects, and is therefore unlikely
Brown, J C; Jiang, X
To identify active phenolic constituents in muscadine grape skin (MGS) extracts and determine interactions among compounds while further exploring their anti-Helicobacter pylori potential in vitro. The inhibitory effects of quercetin and resveratrol, active polyphenols identified in MGS extracts, against H. pylori were investigated. Quercetin and resveratrol significantly (P < 0.05) reduced H. pylori counts regardless of pH with minimal bactericidal concentrations of 256 and 128 μg ml(-1), respectively. MGS extracts displayed the highest efficacy, suggesting additional unidentified compounds not determined in this study. Time-course viability experiments showed a dose-dependent anti-H. pylori response to quercetin and resveratrol. Interestingly, neither quercetin nor resveratrol affected H. pylori outer membrane (OM) integrity as determined by 1-N-phenylnaphthylamine (NPN) uptake assays. However, treatment with MGS extract did increase NPN uptake, indicating OM destabilization possibly by additional unknown components. Furthermore, quercetin was found to enter H. pylori as measured by HPLC supporting intracellular drug accumulation. Quercetin and resveratrol possess strong anti-H. pylori activity in vitro and are independent of pH. Our results also suggest that these compounds do not affect H. pylori OM integrity as previously hypothesized and that the primary antimicrobial activity of quercetin may be linked to interactions with intracellular components. The anti-H. pylori effects of quercetin and resveratrol suggest that these compounds may be useful in the dietary prevention and/or treatment of H. pylori infection. © 2013 The Society for Applied Microbiology.
Zaidi, Syed Faisal
Helicobacter pylori (H. pylori) is one of the most widespread infections in humans worldwide that chronically infects up to 50% of the world’s population. The infection is involved in the pathogenesis of chronic active gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma and gastric cancer, therefore, it has been classified as class I definite carcinogen by the World Health Organization. Despite the established etiological role of H. pylori, its actual distribution and association with related diseases is controversial and there is a large intercountry variation especially among Asian countries. H. pylori infection is more frequent in developing countries like India, Pakistan, and Bangladesh as compared to developed Asian countries like Japan, China and South Korea. However, the frequency of gastric cancer is comparatively lower in India, Pakistan, and Bangladesh with that of Japan, China and South Korea. Such phenomenon of clinical diversity, defined as enigma, is judged by genetic variability of the infecting H. pylori strains, differences in the host genetic background in various ethnic groups, and environmental factors such as dietary habits. Most of the studies have so far focused on the bacterial factor while environmental issues, including dietary components, were not given due attention as one of the factors related with H. pylori associated gastric carcinogenesis. The dietary factor has been suggested to play an important role in H. pylori related carcinogenesis, and in this respect several studies have corroborated the intake of various dietary components as modulatory factors for gastric cancer risk. In this review, such studies, from in vitro experiments to clinical trials, are being focused in detail with respect to enigma associated with H. pylori. It may be conceivably concluded from the available evidence that dietary factor can be a game changer in the scenario of Asian enigma, particularly in high risk population infected with
Zaidi, Syed Faisal
Helicobacter pylori (H. pylori) is one of the most widespread infections in humans worldwide that chronically infects up to 50% of the world's population. The infection is involved in the pathogenesis of chronic active gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma and gastric cancer, therefore, it has been classified as class I definite carcinogen by the World Health Organization. Despite the established etiological role of H. pylori, its actual distribution and association with related diseases is controversial and there is a large intercountry variation especially among Asian countries. H. pylori infection is more frequent in developing countries like India, Pakistan, and Bangladesh as compared to developed Asian countries like Japan, China and South Korea. However, the frequency of gastric cancer is comparatively lower in India, Pakistan, and Bangladesh with that of Japan, China and South Korea. Such phenomenon of clinical diversity, defined as enigma, is judged by genetic variability of the infecting H. pylori strains, differences in the host genetic background in various ethnic groups, and environmental factors such as dietary habits. Most of the studies have so far focused on the bacterial factor while environmental issues, including dietary components, were not given due attention as one of the factors related with H. pylori associated gastric carcinogenesis. The dietary factor has been suggested to play an important role in H. pylori related carcinogenesis, and in this respect several studies have corroborated the intake of various dietary components as modulatory factors for gastric cancer risk. In this review, such studies, from in vitro experiments to clinical trials, are being focused in detail with respect to enigma associated with H. pylori. It may be conceivably concluded from the available evidence that dietary factor can be a game changer in the scenario of Asian enigma, particularly in high risk population infected with
Negrini, R; Savio, A; Appelmelk, B J
Although Helicobacter pylori is recognized as the main cause of chronic gastritis and its associated diseases, very little is known about the pathogenetic mechanisms leading to intestinal metaplasia and atrophic gastritis. We reviewed the data regarding the possible pathogenetic role played by the anti-H. pylori immune responses in the genesis of atrophic gastritis and intestinal metaplasia. Although only type A (corpus-restricted atrophic gastritis), often associated to pernicious anemia, is considered autoimmune in nature, abundant evidence supports the presence of cellular and humoral autoimmune responses also in patients with H. pylori infection. In a mechanism known as antigenic mimicry, highly conserved immunogenic molecules expressed by infectious pathogens may act as a trigger for the induction of humoral and cellular immune responses that cross-react with host cellular antigens. Numerous studies support the view that H. pylori is very effective in inducing antigenic mimicry, and antibodies against H. pylori have been found to cross-react with both antral mucosal cells (the membrane of the secretory canalicular structures of the parietal cells) and gastrin-producing cells. Such autoantibodies were detected both in human infections and in experimental work in rodents. The detection of antibodies that cross-react with H. pylori and various components of the gastric mucosa provides strong support to the view that immune responses against H. pylori not only participate in the pathogenetic mechanisms leading to atrophy in the progressive atrophic gastritis associated with Helicobacter infection but also in the corpus-restricted autoimmune gastritis.
... pill, liquid or pudding that contains tagged carbon molecules. If you have an H. pylori infection, carbon ... uses a special device to detect the carbon molecules. Acid-suppressing drugs known as proton pump inhibitors ( ...
... special substance that has urea. Urea is a waste product the body produces as it breaks down protein. The urea used in the test has been made harmlessly radioactive. If H. pylori are present, the bacteria convert ...
Camenares, Devin; Dulebohn, Daniel P.; Svetlanov, Anton; Karzai, A. Wali
Unproductive ribosome stalling in eubacteria is resolved by the actions of SmpB protein and transfer messenger (tm) RNA. We examined the functional significance of conserved regions of SmpB and tmRNA to the trans-translation process. Our investigations reveal that the N-terminal 20 residues of SmpB, which are located near the ribosomal decoding center, are dispensable for all known SmpB activities. In contrast, a set of conserved residues that reside at the junction between the tmRNA-binding core and the C-terminal tail of SmpB play an important role in tmRNA accommodation. Our data suggest that the highly conserved glycine 132 acts as a flexible hinge that enables movement of the C-terminal tail, thus permitting proper positioning and establishment of the tmRNA open reading frame (ORF) as the surrogate template. To gain further insights into the function of the SmpB C-terminal tail, we examined the tagging activity of hybrid variants of tmRNA and the SmpB protein, in which the tmRNA ORF or the SmpB C-terminal tail was substituted with the equivalent but highly divergent sequences from Francisella tularensis. We observed that the hybrid tmRNA was active but resulted in less accurate selection of the resume codon. Cognate hybrid SmpB was necessary to restore activity. Furthermore, accurate tagging was observed when the identity of the resume codon was reverted from GGC to GCA. Taken together, these data suggest that the engagement of the tmRNA ORF and the selection of the correct translation resumption point are distinct activities that are influenced by independent tmRNA and SmpB determinants. PMID:23986442
Camenares, Devin; Dulebohn, Daniel P; Svetlanov, Anton; Karzai, A Wali
Unproductive ribosome stalling in eubacteria is resolved by the actions of SmpB protein and transfer messenger (tm) RNA. We examined the functional significance of conserved regions of SmpB and tmRNA to the trans-translation process. Our investigations reveal that the N-terminal 20 residues of SmpB, which are located near the ribosomal decoding center, are dispensable for all known SmpB activities. In contrast, a set of conserved residues that reside at the junction between the tmRNA-binding core and the C-terminal tail of SmpB play an important role in tmRNA accommodation. Our data suggest that the highly conserved glycine 132 acts as a flexible hinge that enables movement of the C-terminal tail, thus permitting proper positioning and establishment of the tmRNA open reading frame (ORF) as the surrogate template. To gain further insights into the function of the SmpB C-terminal tail, we examined the tagging activity of hybrid variants of tmRNA and the SmpB protein, in which the tmRNA ORF or the SmpB C-terminal tail was substituted with the equivalent but highly divergent sequences from Francisella tularensis. We observed that the hybrid tmRNA was active but resulted in less accurate selection of the resume codon. Cognate hybrid SmpB was necessary to restore activity. Furthermore, accurate tagging was observed when the identity of the resume codon was reverted from GGC to GCA. Taken together, these data suggest that the engagement of the tmRNA ORF and the selection of the correct translation resumption point are distinct activities that are influenced by independent tmRNA and SmpB determinants.
The Helicobacter pylori HpyAXII restriction–modification system limits exogenous DNA uptake by targeting GTAC sites but shows asymmetric conservation of the DNA methyltransferase and restriction endonuclease components
Humbert, Olivier; Salama, Nina R.
The naturally competent organism Helicobacter pylori encodes a large number of restriction–modification (R–M) systems that consist of a restriction endonuclease and a DNA methyltransferase. R–M systems are not only believed to limit DNA exchange among bacteria but may also have other cellular functions. We report a previously uncharacterized H. pylori type II R–M system, M.HpyAXII/R.HpyAXII. We show that this system targets GTAC sites, which are rare in the H. pylori chromosome but numerous in ribosomal RNA genes. As predicted, this type II R–M system showed attributes of a selfish element. Deletion of the methyltransferase M.HpyAXII is lethal when associated with an active endonuclease R.HpyAXII unless compensated by adaptive mutation or gene amplification. R.HpyAXII effectively restricted both unmethylated plasmid and chromosomal DNA during natural transformation and was predicted to belong to the novel ‘half pipe’ structural family of endonucleases. Analysis of a panel of clinical isolates revealed that R.HpyAXII was functional in a small number of H. pylori strains (18.9%, n = 37), whereas the activity of M.HpyAXII was highly conserved (92%, n = 50), suggesting that GTAC methylation confers a selective advantage to H. pylori. However, M.HpyAXII activity did not enhance H. pylori fitness during stomach colonization of a mouse infection model. PMID:18978016
Bagheri, Nader; Azadegan-Dehkordi, Fatemeh; Rafieian-Kopaei, Mahmoud; Rahimian, Ghorbanali; Asadi-Samani, Majid; Shirzad, Hedaytollah
Helicobacter pylori (H. pylori) usually colonizes the gastric mucosa of more than 50% of the human population, causing an infection that may appear in early childhood and can persist for life. H. pylori is suggested as the main cause of peptic ulcer and chronic gastritis. It is also associated with gastric cancer. Its severity and symptoms depend on environmental factors, host susceptibility and bacterial components, which allow H. pylori to switch between commensalism and pathogenicity. H. pylori is genetically highly variable, and the variability which affects H. pylori virulence factors might be useful in identifying the strains with different degrees of pathogenicity. The geographic distribution of distinct H. pylori genotypes is largely unknown and should be established. The prevalence of more pathogenic genotypes in certain areas may have important epidemiological consequences. It also might be associated with the severity of H. pylori related diseases in such regions. Given that Iran is located in the Middle East and Asian populations have revealed high levels of gastric cancer, it is of clinical interest to clarify the potential of H. pylori virulence markers in predicting the associated clinical outcomes. In this review, clinical relevance of adhesion molecules and significant virulence factors of H. pylori in Iranian patients with gastrointestinal diseases are discussed in comparison to other countries. Copyright © 2016 Elsevier Ltd. All rights reserved.
Chmiela, Magdalena; Miszczyk, Eliza; Rudnicka, Karolina
In this review, we discuss the findings and concepts underlying the "persistence mechanisms" of Helicobacter pylori (H. pylori), a spiral-shaped, Gram-negative rod bacterium that was discovered as a gastric pathogen by Marshall and Warren in 1984. H. pylori colonizes the gastric mucosa of nearly half of the human population. Infections appear in early childhood and, if not treated, persist for life. The presence or absence of symptoms and their severity depend on multiple bacterial components, host susceptibility and environmental factors, which allow H. pylori to switch between pathogenicity and commensalism. Many studies have shown that H. pylori components may facilitate the colonization process and the immune response of the host during the course of H. pylori infection. These H. pylori-driven interactions might result from positive or negative modulation. Among the negative immunomodulators, a prominent position is occupied by a vacuolating toxin A (VacA) and cytotoxin-associated gene A (CagA) protein. However, in light of the recent studies that are presented in this review, it is necessary to enrich this panel with H. pylori lipopolysaccharide (LPS). Together with CagA and VacA, LPS suppresses the elimination of H. pylori bacteria from the gastric mucosa by interfering with the activity of innate and adaptive immune cells, diminishing the inflammatory response, and affecting the adaptive T lymphocyte response, thus facilitating the development of chronic infections. The complex strategy of H. pylori bacteria for survival in the gastric mucosa of the host involves both structural modifications of LPS lipid A to diminish its endotoxic properties and the expression and variation of Lewis determinants, arranged in O-specific chains of H. pylori LPS. By mimicking host components, this phenomenon leaves these bacteria "invisible" to immune cells. Together, these mechanisms allow H. pylori to survive and live for many years within their hosts.
Chmiela, Magdalena; Miszczyk, Eliza; Rudnicka, Karolina
In this review, we discuss the findings and concepts underlying the “persistence mechanisms” of Helicobacter pylori (H. pylori), a spiral-shaped, Gram-negative rod bacterium that was discovered as a gastric pathogen by Marshall and Warren in 1984. H. pylori colonizes the gastric mucosa of nearly half of the human population. Infections appear in early childhood and, if not treated, persist for life. The presence or absence of symptoms and their severity depend on multiple bacterial components, host susceptibility and environmental factors, which allow H. pylori to switch between pathogenicity and commensalism. Many studies have shown that H. pylori components may facilitate the colonization process and the immune response of the host during the course of H. pylori infection. These H. pylori-driven interactions might result from positive or negative modulation. Among the negative immunomodulators, a prominent position is occupied by a vacuolating toxin A (VacA) and cytotoxin-associated gene A (CagA) protein. However, in light of the recent studies that are presented in this review, it is necessary to enrich this panel with H. pylori lipopolysaccharide (LPS). Together with CagA and VacA, LPS suppresses the elimination of H. pylori bacteria from the gastric mucosa by interfering with the activity of innate and adaptive immune cells, diminishing the inflammatory response, and affecting the adaptive T lymphocyte response, thus facilitating the development of chronic infections. The complex strategy of H. pylori bacteria for survival in the gastric mucosa of the host involves both structural modifications of LPS lipid A to diminish its endotoxic properties and the expression and variation of Lewis determinants, arranged in O-specific chains of H. pylori LPS. By mimicking host components, this phenomenon leaves these bacteria “invisible” to immune cells. Together, these mechanisms allow H. pylori to survive and live for many years within their hosts. PMID:25110419
Suzuki, Hidekazu; Nishizawa, Toshihiro; Hibi, Toshifumi
Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcers and gastric cancer. H. pylori eradication has been shown to have a prophylactic effect against gastric cancer. According to several international guidelines, the first-line therapy for treating H. pylori infection consists of a proton pump inhibitor (PPI) or ranitidine bismuth citrate, with any two antibiotics among amoxicillin, clarithromycin and metronidazole, given for 7-14 days. However, even with these recommended regimens, H. pylori eradication failure is still seen in more than 20% of patients. The failure rate for first-line therapy may be higher in actual clinical practice, owing to the indiscriminate use of antibiotics. The recommended second-line therapy is a quadruple regimen composed of tetracycline, metronidazole, a bismuth salt and a PPI. The combination of PPI-amoxicillin-levofloxacin is a good option as second-line therapy. In the case of failure of second-line therapy, the patients should be evaluated using a case-by-case approach. European guidelines recommend culture before the selection of a third-line treatment based on the microbial antibiotic sensitivity. H. pylori isolates after two eradication failures are often resistant to both metronidazole and clarithromycin. The alternative candidates for third-line therapy are quinolones, tetracycline, rifabutin and furazolidone; high-dose PPI/amoxicillin therapy might also be promising.
Arimoto-Kobayashi, Sakae; Ohta, Kaori; Yuhara, Yuta; Ayabe, Yuka; Negishi, Tomoe; Okamoto, Keinosuke; Nakajima, Yoshihiro; Ishikawa, Takeshi; Oguma, Keiji; Otsuka, Takanao
Epidemiological studies have demonstrated a close association between infection with Helicobacter pylori (H.pylori) and the development of gastric carcinoma. Chronic H.pylori infection increases the frequency of mutation in gastric epithelial cells. However, the mechanism by which infection of H.pylori leads to mutation in gastric epithelial cells is unclear. We suspected that components in H.pylori may be related to the mutagenic response associated with DNA alkylation, and could be detected with the Ames test using a more sensitive strain for alkylating agents. Our investigation revealed that an extract of H.pylori was mutagenic in the Ames test with Salmonella typhimurium YG7108, which is deficient in the DNA repair of O(6)-methylguanine. The extract of H.pylori may contain methylating or alkylating agents, which might induce O (6)-alkylguanine in DNA. Mutagenicity of the alkylating agents N-methyl-N-nitrosourea (MNU) and N-methyl-N'-nitro-N-nitrosoguanidine in the Ames test with S.typhimurium TA1535 was enhanced significantly in the presence of the extract of H.pylori. The tested extracts of H.pylori resulted in a significant induction of micronuclei in human-derived lymphoblastoid cells. Heat instability and dialysis resistance of the extracts of H.pylori suggest that the mutagenic component in the extracts of H.pylori is a heat-unstable large molecule or a heat-labile small molecule strongly attached or adsorbed to a large molecule. Proteins in the extracts of H.pylori were subsequently fractionated using ammonium sulphate precipitation. However, all fractions expressed enhancing effects toward MNU mutagenicity. These results suggest the mutagenic component is a small molecule that is absorbed into proteins in the extract of H.pylori, which resist dialysis. Continuous and chronic exposure of gastric epithelial cells to the alkylative mutagenic component from H.pylori chronically infected in the stomach might be a causal factor in the gastric carcinogenesis
Owen, R J
The discovery and first isolation of H. pylori in pure culture from gastric biopsies in 1982 provided the basis for a completely new area of microbiology. Since then, H. pylori has been an intensively pursued topic world-wide, and extensive data have been acquired on all aspects of its basic microbiology, both at the conventional phenotypic level and at the molecular level. H. pylori is a remarkable microorganism because of its ability to readily colonize a major proportion of human population worldwide and to persist successfully for long periods (probably decades) in a hostile environment. At the same time it interacts with the host immune system in such a way as to permit long-term survival. Blaser (1993) proposed a model in which both host and parasite adapt to down regulate inflammatory phenomena to promote survival. Urease production by H. pylori (an important factor in that process) is one of its most distinct features with a key role in its success as an infective agent. Another less obvious yet highly significant feature of H. pylori is the ability to achieve a high degree of interstrain diversity in genomic DNA nucleotide sequences, while maintaining overall genetic homology and phenotypic homogeneity amongst strains. The selective advantage this diversity provides the bacterium is not understood. A key objective of future microbiological studies should be to understand the population genetic structure of H. pylori. Most species of bacteria are clonal in natural population structure, yet all genomic data suggest the contrary is true for H. pylori. Furthermore, it is not clear if all strains of H. pylori are equally pathogenic, and that some subsets may possess additional pathogenicity factors that are responsible for the development of different disease pathologies. A phylogenetic framework of the genetic relationships of the clones within H. pylori would enable an examination of the total genetic diversity, with respect to ethnic or geographical
Tufano, M A; Rossano, F; Catalanotti, P; Liguori, G; Capasso, C; Ceccarelli, M T; Marinelli, P
Studies were carried out on some biological activities of Helicobacter pylori porins in vitro. We extracted and purified a porin with an apparent molecular mass of 30 kDa. Human polymorphonuclear leukocytes preincubated with H. pylori porins showed a decrease of chemotaxis, of adherence to nylon wool, and of chemiluminescence. Used as chemotaxins in place of zymosan-activated serum or as chemotaxinogens in place of zymosan, the porins induced polymorphonuclear leukocyte migration. Human monocytes and lymphocytes cultivated in the presence of H. pylori porins released cytokines. Release of the various cytokines studied was obtained with differentiated kinetics and at various porin concentrations. Starting only 3 h after culture, tumor necrosis factor alpha is released quickly, reaching a peak at 18 h, at a porin concentration of 1 microgram/ml/10(6) cells. Interleukin-6 (IL-6) appears later, with a peak at 10 micrograms/ml/10(6) cells, while IL-8 is released after 6 h of culture, with a peak at 24 h, at a porin concentration of 10 micrograms/ml/10(6) cells, while IL-8 is released after 6 h of culture, with a peak at 24 h, at a porin concentration of 10 micrograms/ml/10(6) cells. Lymphocytes stimulated by H. pylori porins release gamma interferon after 18 h of culture at higher concentrations of porins (20 micrograms/ml/10(6) cells). Granulocyte macrophage colony-stimulating factor is released from 6 to 48 h at a concentration of 1 microgram/ml/10(6) cells, while both IL-3 and IL-4 are released after 18 h of culture at different porin concentrations (0.1 and 1 microgram/ml/10(6) cells, respectively). Our results lead us to think that during H. pylori infection, surface components, porins in particular, are able to induce a series of chain reactions ranging from the inflammatory to the immunological responses. Images PMID:8132346
Skoog, Emma C; Sjöling, Åsa; Navabi, Nazanin; Holgersson, Jan; Lundin, Samuel B; Lindén, Sara K
Helicobacter pylori colonizes the mucus niche of the gastric mucosa and is a risk factor for gastritis, ulcers and cancer. The main components of the mucus layer are heavily glycosylated mucins, to which H. pylori can adhere. Mucin glycosylation differs between individuals and changes during disease. Here we have examined the H. pylori response to purified mucins from a range of tumor and normal human gastric tissue samples. Our results demonstrate that mucins from different individuals differ in how they modulate both proliferation and gene expression of H. pylori. The mucin effect on proliferation varied significantly between samples, and ranged from stimulatory to inhibitory, depending on the type of mucins and the ability of the mucins to bind to H. pylori. Tumor-derived mucins and mucins from the surface mucosa had potential to stimulate proliferation, while gland-derived mucins tended to inhibit proliferation and mucins from healthy uninfected individuals showed little effect. Artificial glycoconjugates containing H. pylori ligands also modulated H. pylori proliferation, albeit to a lesser degree than human mucins. Expression of genes important for the pathogenicity of H. pylori (babA, sabA, cagA, flaA and ureA) appeared co-regulated in response to mucins. The addition of mucins to co-cultures of H. pylori and gastric epithelial cells protected the viability of the cells and modulated the cytokine production in a manner that differed between individuals, was partially dependent of adhesion of H. pylori to the gastric cells, but also revealed that other mucin factors in addition to adhesion are important for H. pylori-induced host signaling. The combined data reveal host-specific effects on proliferation, gene expression and virulence of H. pylori due to the gastric mucin environment, demonstrating a dynamic interplay between the bacterium and its host.
Amieva, Manuel; Peek, Richard M
Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of a complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data have indicated that subtle mismatches between host and microbe genetic traits greatly affect the risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness show the sophisticated relationship between H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori's activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism. Copyright © 2016. Published by Elsevier Inc.
Olofsson, Annelie; Vallström, Anna; Petzold, Katja; Tegtmeyer, Nicole; Schleucher, Jürgen; Carlsson, Sven; Haas, Rainer; Backert, Steffen; Wai, Sun Nyunt; Gröbner, Gerhard; Arnqvist, Anna
Helicobacter pylori can cause peptic ulcer disease and/or gastric cancer. Adhesion of bacteria to the stomach mucosa is an important contributor to the vigour of infection and resulting virulence. H. pylori adheres primarily via binding of BabA adhesins to ABO/Lewis b (Leb) blood group antigens and the binding of SabA adhesins to sialyl-Lewis x/a (sLex/a) antigens. Similar to most Gram-negative bacteria, H. pylori continuously buds off vesicles and vesicles derived from pathogenic bacteria often include virulence-associated factors. Here we biochemically characterized highly purified H. pylori vesicles. Major protein and phospholipid components associated with the vesicles were identified with mass spectroscopy and nuclear magnetic resonance. A subset of virulence factors present was confirmed by immunoblots. Additional functional and biochemical analysis focused on the vesicle BabA and SabA adhesins and their respective interactions to human gastric epithelium. Vesicles exhibit heterogeneity in their protein composition, which were specifically studied in respect to the BabA adhesin. We also demonstrate that the oncoprotein, CagA, is associated with the surface of H. pylori vesicles. Thus, we have explored mechanisms for intimate H. pylori vesicle–host interactions and found that the vesicles carry effector-promoting properties that are important to disease development. PMID:20659286
Jia, Keran; An, Liyun; Wang, Fukun; Shi, Lanchun; Ran, Xiangyang; Wang, Xianling; He, Zhanguo; Chen, Jing
To investigate the effect of military stress on immune response and Helicobacter pylori stomach infections. In this prospective, observational study, the Symptom Checklist-90 questionnaire was completed by military recruits before and following a 3-month basic training programme. H. pylori immunoglobulin (Ig)G levels, C(14)-urea breath-test values and levels of cortisol, catecholamine, and certain humoral and cellular immune responses were measured before and after the basic training. For 60 military recruits, somatization, depression and paranoid ideation scores were significantly increased after, compared with before, basic training. Post-training H. pylori IgG detection revealed three additional cases of H. pylori infection. Post-training C(14)-urea breath-test values were significantly higher compared with before training - thus suggesting higher levels of H. pylori colonization in the stomach. Post-training cortisol and catecholamine levels were increased, while serum IgG levels were decreased; complement component (C)3 and C4 levels remained unchanged. Post-training CD4(+) and CD8(+) T-cell percentages and the CD4(+)/CD8(+) ratio were significantly reduced compared with before training. Serum interleukin (IL)-2 levels were lower and IL-10 levels were higher following training and there was a significant decrease in the IL-2/IL-10 ratio. Military stress may reduce humoral and cellular immune responses and may aggravate the severity of H. pylori infection. © The Author(s) 2016.
Lawal, Oladejo O; Rotimi, Olorunda; Okeke, Iruka
To determine the prevalence and disease association of Helicobacter pylori (H. pylori) in dyspeptic patients in southwest Nigeria. Obafemi Awolowo University Teaching Hospitals Complex, Ile-lfe, Nigeria. Consecutive dyspeptic patients for upper gastrointestinal endoscopy from January 1996 to March 1997 were investigated for H. pylori in gastric biopsy by histopathology and culture. Patients without gastroduodenal ulcerations or neoplastic lesions constituted the nonulcer dyspeptic (NUD) group. 138 (92 males, 46 females) patients aged 4.5-85 years [mean (7) = 45+/-SD 17.8 years] who had upper gastrointestinal endoscopy were analyzed for presence of H. pylori. Eighty-three had histopathology alone, while 55 others had both histology and culture. Endoscopic diagnosis included duodenal ulcer (DU) (n=35, 23%); gastric ulcer (n=4, 3%); gastric cancer (n=14, 9%); NUD, including gastritis (n=49, 32%); duodenitis (n=47, 31%); and normal (n=16, 11%). Overall, H. pylori was positive in 107 of 138 (77.5%) patients. There was a significant association of H. pylori with DU and NUD (p<0.000). Three-quarters of cases of normal endoscopy harbored H. pylori. The finding of 80% and 85% H. pylori in gastritis and duodenitis, respectively, was of interest. These findings suggest that DU and NUD were the main clinical expressions of H. pylori infection in southwest Nigerian dyspeptic patients similar to what is found in developed nations. Of note is the high incidence of H. pylori in endoscopically normal patients.
Roma, Eleftheria; Miele, Erasmo
This review includes the main pediatric studies published from April 2014 to March 2015. The host response of Treg cells with increases in FOXP3 and TGF-β1 combined with a reduction in IFN-γ by Teff cells may contribute to Helicobacter pylori susceptibility in children. Genotypic variability in H. pylori strains influences the clinical manifestation of the infection. Helicobacter pylori infection is associated with variables indicative of a crowded environment and poor living conditions, while breast-feeding has a protective effect. Intrafamilial infection, especially from mother to children and from sibling to sibling, is the dominant transmission route. Studies showed conflicting results regarding the association between H. pylori infection and iron deficiency anemia. One study suggests that H. pylori eradication plays a role in the management of chronic immune thrombocytopenic purpura in H. pylori-infected children and adolescents. The prevalence of H. pylori was higher in chronic urticaria patients than in controls and, following H. pylori eradication, urticarial symptoms disappeared. An inverse relationship between H. pylori infection and allergic disease was reported. Antibiotic resistance and insufficient compliance to treatment limit the efficacy of eradication therapy. Sequential therapy had no advantage over standard triple therapy. In countries where H. pylori infection is prevalent, studies focusing on virulence factors and antibiotic susceptibility may provide anticipation of the prognosis and may be helpful to reduce morbidity and mortality.
Dou, Wenhuan; Li, Juan; Xu, Liming; Zhu, Jianhong; Hu, Kewei; Sui, Zhenyu; Wang, Jianzong; Xu, Lingling; Wang, Shaofeng; Yin, Guojian
Abstract Background: Halitosis is used to describe any disagreeable odor of expired air regardless of its origin. Numerous trials published have investigated the relation between Helicobacter pylori (H pylori) infection and halitosis, and even some regimes of H pylori eradication have been prescribed to those patients with halitosis in the clinic. We conducted a meta-analysis to define the correlation between H pylori infection and halitosis. Objectives: To evaluate whether there is a real correlation between H pylori infection and halitosis, and whether H pylori eradication therapy will help relieve halitosis. Methods: We searched several electronic databases (The Cochrane Library, MEDLINE, EMBASE, PubMed, Web of Science, and Wanfangdata) up to December 2015. Studies published in English and Chinese were considered in this review. After a final set of studies was identified, the list of references reported in the included reports was reviewed to identify additional studies. Screening of titles and abstracts, data extraction and quality assessment was undertaken independently and in duplicate. All analyses were done using Review Manager 5.2 software. Results: A total of 115 articles were identified, 21 of which met the inclusion criteria and presented data that could be used in the analysis. The results showed that the OR of H pylori infection in the stomach between halitosis-positive patients and halitosis-negative patients was 4.03 (95% CI: 1.41–11.50; P = 0.009). The OR of halitosis between H pylori-positive patients and H pylori-negative patients was 2.85 (95% CI: 1.40–5.83; P = 0.004); The RR of halitosis after successful H pylori eradication in those H pylori-infected halitosis-positive patients was 0.17 (95% CI: 0.08–0.39; P <0.0001), compared with those patients without successful H pylori eradication. And the RR of halitosis before successful H pylori eradication therapy was 4.78 (95% CI: 1.45–15.80; P = 0.01), compared with after successful H
Helicobacter pylori (H. pylori) infection-related diseases are known to include gastritis, gastric and duodenal ulcer, gastric cancer, gastric MALT lymphoma, idiopathic thrombocytopenic purpura, iron-deficient anemia, urticaria, reflux esophagitis, and some lifestyle-related diseases. It is indicated that homocysteine involved with arteriosclerosis induces lifestyle-related diseases. Homocysteine is decomposed to methionine and cysteine (useful substances) in the liver, through the involvement of vitamin B₁₂ (VB₁₂) and folic acid. However, deficiency of VB₁₂ and folic acid induces an increase in unmetabolized homocysteine stimulating active oxygen and promoting arteriosclerosis. VB₁₂ and folic acid are activated by the intrinsic factors of gastric parietal cells and gastric acid. The question of whether homocysteine, as a trigger of arteriosclerosis, was influenced by H. pylori infection was investigated. H. pylori infection induces atrophy of the gastric mucosa, and the function of parietal cells decreases with the atrophy to inactivate its intrinsic factor. The inactivation of the intrinsic factor causes a deficiency of VB₁₂ and folic acid to increase homocysteine's chances of triggering arteriosclerosis. The significance and usefulness of H. pylori eradication therapy was evaluated for its ability to prevent arteriosclerosis that induces lifestyle-related diseases. Persons with positive and negative results of H. pylori infection were divided into a group of those aged 65 years or more (early and late elderly) and a group of those under 65 years of age, and assessed for gastric juice. For twenty-five persons from each group who underwent gastrointestinal endoscopy, the degree of atrophy of the gastric mucosa was observed. Blood homocysteine was measured as a novel index of arteriosclerosis, as well as VB₁₂ and folic acid that affect the metabolism of homocysteine, and then activated by gastric acid and intrinsic factors. Their
Shiota, Seiji; Murakawi, Kazunari; Suzuki, Rumiko; Fujioka, Toshio; Yamaoka, Yoshio
The prevalence of Helicobacter pylori infection is gradually decreasing in Japan. On the main island of Japan, nearly all H. pylori isolates possess cagA and vacA with strong virulence. However, less virulent H. pylori strains are frequently found in Okinawa where cases of gastric cancer are the lowest in Japan. Eradication therapy for peptic ulcer, idiopathic thrombocytopenic purpura, gastric mucosa-associated lymphoid tissue lymphoma and early gastric cancer after endoscopic resection has been approved by the Japanese national health insurance system. However, the Japanese Society for Helicobacter Research recently stated that all ‘H. pylori infection’ was considered as the indication for eradication irrespective of the background diseases. To eliminate H. pylori in Japan, the Japanese health insurance system should approve the eradication of all H. pylori infections. PMID:23265147
Shiota, Seiji; Murakawi, Kazunari; Suzuki, Rumiko; Fujioka, Toshio; Yamaoka, Yoshio
The prevalence of Helicobacter pylori infection is gradually decreasing in Japan. On the main island of Japan, nearly all H. pylori isolates possess cagA and vacA with strong virulence. However, less virulent H. pylori strains are frequently found in Okinawa where cases of gastric cancer are the lowest in Japan. Eradication therapy for peptic ulcer, idiopathic thrombocytopenic purpura, gastric mucosa-associated lymphoid tissue lymphoma and early gastric cancer after endoscopic resection has been approved by the Japanese national health insurance system. However, the Japanese Society for Helicobacter Research recently stated that all 'H. pylori infection' was considered as the indication for eradication irrespective of the background diseases. To eliminate H. pylori in Japan, the Japanese health insurance system should approve the eradication of all H. pylori infections.
Suerbaum, Sebastian; Smith, John Maynard; Bapumia, Khairun; Morelli, Giovanna; Smith, Noel H.; Kunstmann, Erdmute; Dyrek, Isabelle; Achtman, Mark
Sequences of three gene fragments (flaA, flaB, and vacA) from Helicobacter pylori strains isolated from patients in Germany, Canada, and South Africa were analyzed for diversity and for linkage equilibrium by using the Homoplasy Test and compatibility matrices. Horizontal genetic exchange in H. pylori is so frequent that different loci and polymorphisms within each locus are all at linkage equilibrium. These results indicate that H. pylori is panmictic. Comparisons with sequences from Escherichia coli, Neisseria meningitidis, and Drosophila melanogaster showed that recombination in H. pylori was much more frequent than in other species. In contrast, when multiple family members infected with H. pylori were investigated, some strains were indistinguishable at all three loci. Thus, H. pylori is clonal over short time periods after natural transmission. PMID:9770535
Ghrelin is primarily secreted from the stomach and has been implicated in the coordination of eating behavior and weight regulation. Ghrelin also plays an essential role in the mechanism of gastric mucosal defense. Thus, it is important to clarify which diseases primarily influence changes in plasma ghrelin concentrations. Helicobacter pylori (H pylori) infection is involved in the pathogenesis of gastritis, gastric and duodenal ulcer, gastric carcinoma, and mucosa-associated lymphoid tissue lymphoma. H pylori eradication is related to body weight change. Compared, H pylori infected and negative subjects with normal body mass index, plasma ghrelin concentration, gastric ghrelin mRNA, and the number of ghrelin producing cells in gastric mucosa are significantly lower in H pylori infected subjects than in H pylori-negative controls. Plasma ghrelin concentration decreases with the progression of gastric atrophy. Impaired gastric ghrelin production in association with atrophic gastritis induced by H pylori infection accounts for the decrease in plasma ghrelin concentration. However, the ratio of plasma acylated ghrelin to total ghrelin levels is higher in patients with chronic atrophic gastritis than in healthy subjects. This may result from the compensatory increase in plasma active ghrelin concentration in response to gastric atrophy. After H pylori eradication, gastric preproghrelin mRNA expression is increased nearly 4-fold in most cases. However, changes in plasma ghrelin concentrations before and after H pylori cure are not associated with the gastric ghrelin production. Plasma ghrelin changes are inversely correlated with both body weight change and initial plasma ghrelin levels. PMID:19009647
Cao, Donghui; Jiang, Jing; You, Lili; Jia, Zhifang; Tsukamoto, Tetsuya; Cai, Hongke; Wang, Shidong; Hou, Zhen; Suo, Yue-er; Cao, Xueyuan
18β-Glycyrrhetinic acid (GRA), a major component of Glycyrrhiza glabra, is widely used therapeutically in clinic. In this study, the effect of GRA on Helicobacter pylori- (H. pylori-) infected gastritis was investigated in Mongolian gerbils in vivo. The gerbils were randomly divided into groups: uninfected; H. pylori-infected; H. pylori + antibiotics (clarithromycin, amoxicillin, and esomeprazole); and H. pylori + GRA. The gastric intraluminal pH value, histopathological changes, and the expression levels of inflammation-related cytokines (IL-1β, TNF-α, COX-2, and iNOS) were investigated. The results showed that, in the H. pylori + GRA group, the intraluminal gastric pH value was lower (2.14 ± 0.08 versus 3.17 ± 0.23, P < 0.05), erosion and hyperplasia were alleviated, the infiltration of neutrophils and mononuclear cells was attenuated (P < 0.05), and the expression levels of TNF-α, IL-1β, COX-2, and iNOS were decreased (P < 0.05) compared with the H. pylori-infected group. There was no significant difference in results between the H. pylori + GRA group and the H. pylori + antibiotics group. This study indicated that GRA significantly attenuated H. pylori-infected gastritis in gerbils and has the potential to be developed as a new therapeutic drug. PMID:27006947
Pan-in, Porntip; Tachapruetinun, Amornset; Chaichanawongsaroj, Nuntaree; Banlunara, Wijit; Suksamrarn, Sunit; Wanichwecharungruang, Supason
To combat the resistance of Helicobacter pylori to antibiotics through the use of Garcinia mangostana extract (GME) in the form that can be localized at stomach mucosa. GME and its major active component, α-mangostin, are encapsulated into the moderately acid stable mucoadhesive nanocarriers, and tested for anti-H. pylori and antiadhesion activities in vitro and their ability to eradicate H. pylori in infected mice. The two in vitro activities are observed and are enhanced when the materials are encapsulated into nanocarriers. Preliminary in vivo tests revealed the ability to combat H. pylori in mice following oral administration of the encapsulated GME, but not the unencapsulated GME. Nanoencapsulated GME is a potential anti-H. pylori agent.
Three strains of Helicobacter pylori (H. pylori) were studied to determine their resistance to chloramination. H. pylori is an organism listed on the U.S. Environmental Protection Agency’s (USEPA) Contaminant Control List (CCL). H. pylori was exposed to 2ppm of pre-formed monoc...
Three strains of Helicobacter pylori (H. pylori) were studied to determine their resistance to chloramination. H. pylori is an organism listed on the U.S. Environmental Protection Agency’s (USEPA) Contaminant Control List (CCL). H. pylori was exposed to 2ppm of pre-formed monoc...
Linz, Bodo; Balloux, François; Moodley, Yoshan; Manica, Andrea; Liu, Hua; Roumagnac, Philippe; Falush, Daniel; Stamer, Christiana; Prugnolle, Franck; van der Merwe, Schalk W; Yamaoka, Yoshio; Graham, David Y; Perez-Trallero, Emilio; Wadstrom, Torkel; Suerbaum, Sebastian; Achtman, Mark
Infection of the stomach by Helicobacter pylori is ubiquitous among humans. However, although H. pylori strains from different geographic areas are associated with clear phylogeographic differentiation, the age of an association between these bacteria with humans remains highly controversial. Here we show, using sequences from a large data set of bacterial strains that, as in humans, genetic diversity in H. pylori decreases with geographic distance from east Africa, the cradle of modern humans. We also observe similar clines of genetic isolation by distance (IBD) for both H. pylori and its human host at a worldwide scale. Like humans, simulations indicate that H. pylori seems to have spread from east Africa around 58,000 yr ago. Even at more restricted geographic scales, where IBD tends to become blurred, principal component clines in H. pylori from Europe strongly resemble the classical clines for Europeans described by Cavalli-Sforza and colleagues. Taken together, our results establish that anatomically modern humans were already infected by H. pylori before their migrations from Africa and demonstrate that H. pylori has remained intimately associated with their human host populations ever since.
Smith, Sinéad M
The gram-negative bacterium Helicobacter pylori (H. pylori) infects the stomachs of approximately half of the world’s population. Although infection induces an immune response that contributes to chronic gastric inflammation, the response is not sufficient to eliminate the bacterium. H. pylori infection causes peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Disease outcome is linked to the severity of the host inflammatory response. Gastric epithelial cells represent the first line of innate immune defence against H. pylori, and respond to infection by initiating numerous cell signalling cascades, resulting in cytokine induction and the subsequent recruitment of inflammatory cells to the gastric mucosa. Pathogen recognition receptors of the Toll-like receptor (TLR) family mediate many of these cell signalling events. This review discusses recent findings on the role of various TLRs in the recognition of H. pylori in distinct cell types, describes the TLRs responsible for the recognition of individual H. pylori components and outlines the influence of innate immune activation on the subsequent development of the adaptive immune response. The mechanistic identification of host mediators of H. pylori-induced pathogenesis has the potential to reveal drug targets and opportunities for therapeutic intervention or prevention of H. pylori-associated disease by means of vaccines or immunomodulatory therapy. PMID:25133016
Moodley, Yoshan; Manica, Andrea; Liu, Hua; Roumagnac, Philippe; Falush, Daniel; Stamer, Christiana; Prugnolle, Franck; van der Merwe, Schalk W.; Yamaoka, Yoshio; Graham, David Y.; Perez-Trallero, Emilio; Wadstrom, Torkel; Suerbaum, Sebastian; Achtman, Mark
Infection of the stomach by Helicobacter pylori is ubiquitous among humans. However, while H. pylori strains from different geographic areas are associated with clear phylogeographic differentiation1-4, the age of an association between these bacteria with humans remains highly controversial5, 6. Here we show, using sequences from a large dataset of bacterial strains that, as in humans, genetic diversity in H. pylori decreases with geographic distance from East Africa, the cradle of modern humans. We also observe similar clines of genetic isolation by distance (IBD) for both H. pylori and its human host at a worldwide scale. Like humans, simulations indicate that H. pylori seems to have spread from East Africa around 58,000 years ago. Even at more restricted geographic scales, where IBD tends to become blurred, principal component clines in H. pylori from Europe strongly resemble the classical clines for Europeans described by Cavalli-Sforza and colleagues7. Taken together, our results establish that anatomically modern humans were already infected by H. pylori prior to their migrations from Africa and demonstrate that H. pylori has remained intimately associated with their human host populations ever since. PMID:17287725
Pacifico, Lucia; Anania, Caterina; Osborn, John F; Ferraro, Flavia; Chiesa, Claudio
Although evidence is emerging that the prevalence of Helicobacter pylori (H. pylori) is declining in all age groups, the understanding of its disease spectrum continues to evolve. If untreated, H. pylori infection is lifelong. Although H. pylori typically colonizes the human stomach for many decades without adverse consequences, children infected with H. pylori can manifest gastrointestinal diseases. Controversy persists regarding testing (and treating) for H. pylori infection in children with recurrent abdominal pain, chronic idiopathic thrombocytopenia, and poor growth. There is evidence of the role of H. pylori in childhood iron deficiency anemia, but the results are not conclusive. The possibility of an inverse relationship between H. pylori and gastroesophageal reflux disease, as well as childhood asthma, remains a controversial question. A better understanding of the H. pylori disease spectrum in childhood should lead to clearer recommendations about testing for and treating H. pylori infection in children who are more likely to develop clinical sequelae. PMID:21049552
... TOPIC Peptic Ulcers Stool Tests Stool Test: Bacteria Culture Stool Test: Giardia Antigen Stool Test: H. Pylori Antigen Helicobacter pylori X-Ray Exam: Upper Gastrointestinal Tract (Upper GI) Ugh! Ulcers Ulcers Contact Us Print Resources Send to a Friend Permissions Guidelines ...
Potamitis, Georgios S; Axon, Anthony T R
Helicobacter pylori is responsible for most peptic ulcers, plays a role in functional dyspepsia and is thought by some to influence the course of gastroesophageal reflux disease. This article addresses recent studies that have been published in connection with these diseases. H. pylori-associated peptic ulcer is declining in prevalence but the incidence of perforation and bleeding remains high especially in the elderly. All H. pylori associated peptic ulcers should be treated by eradication of the infection. Dyspepsia is a common disorder that affects up to 25% of the population. About 8% of cases that are infected with H. pylori will respond to treatment of the infection. The association between H. pylori and gastroesophageal reflux disease continues to be debated, a number of studies have shown that there is a negative association between H. pylori infection and Gastroesophageal reflux disease but treatment of H. pylori has not been shown to induce reflux or to affect the response to medication. Gastric atrophy is known to extend when acid suppression is used in infected patients implying that H. pylori treatment should be used in infected patients who are to undergo long-term Proton Pump Inhibitor therapy.
Eusebi, Leonardo H; Zagari, Rocco M; Bazzoli, Franco
Medline and PubMed databases were searched on epidemiology of Helicobacter pylori for the period of April 2013-March 2014. Several studies have shown that the prevalence of H. pylori is still high in most countries. In north European and North American populations, about one-third of adults are still infected, whereas in south and east Europe, South America, and Asia, the prevalence of H. pylori is often higher than 50%. H. pylori remains highly prevalent in immigrants coming from countries with high prevalence of H. pylori. However, the lower prevalence of infection in the younger generations suggests a further decline of H. pylori prevalence in the coming decades. Low socioeconomic conditions in childhood are confirmed to be the most important risk factors for H. pylori infection. Although the way the infection is transmitted is still unclear, interpersonal transmission appears to be the main route. Finally, H. pylori recurrence after successful eradication can still occur, but seems to be an infrequent event.
Benoit, Stéphane L.; Miller, Erica F.
The transition metal nickel (Ni) is critical for the pathogenicity of Helicobacter pylori. Indeed the element is a required component of two enzymes, hydrogenase and urease, that have been shown to be important for in vivo colonization of the host gastric mucosa. Urease accounts for up to 10% of the total cellular H. pylori protein content, and therefore the bacterial Ni demand is very high. H. pylori possess two small and abundant histidine-rich, Ni-binding proteins, Hpn and Hpn-like, whose physiological role in the host have not been investigated. In this study, special husbandry conditions were used to control Ni levels in the host (mouse), including the use of Ni-free versus Ni-supplemented food. The efficacy of each diet was confirmed by measuring the Ni concentrations in sera of mice fed with either diet. Colonization levels (based on rank tests) of the Δhpn Δhpn-like double mutants isolated from the mice provided Ni-deficient chow were statistically lower than those for mice given Ni in their diet. In contrast, H. pylori wild-type colonization levels were similar in both host groups (e.g., regardless of Ni levels). Our results indicate that the gastric pathogen H. pylori can utilize stored Ni via defined histidine-rich proteins to aid colonization of the host. PMID:23230291
Amieva, Manuel; Peek, Richard M.
Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data indicate that subtle mismatches between host and microbe genetic traits greatly affect risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness demonstrates the sophisticated relationship among H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori’s activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism. PMID:26385073
Ustün, Osman; Ozçelik, Berrin; Akyön, Yakut; Abbasoglu, Ufuk; Yesilada, Erdem
Cistus laurifolius flower buds are used traditionally in folk medicine against gastric ailments. In a prior study we showed that the chloroform extract of Cistus laurifolius had a potent anti-ulcer activity. It has been known that there is a causal relationship between peptic ulcer and Helicobacter pylori infection. Then in a previous study, we demonstrated that chloroform extract of Cistus laurifolius possessed a significant anti-Helicobacter pylori activity. We designed this study to isolate and define the active component(s) involved in the anti-Helicobacter pylori activity of the extract through activity-guided fractionation procedures. The chloroform extract was fractionated by using various chromatography techniques, i.e., Sephadex LH-20 column chromatography and preparative thin layer chromatography and six compounds were isolated (1-6). Each of these six compounds' anti-Helicobacter pylori activity was tested in vitro and was measured as minimum inhibition concentration (MIC) values by using agar dilution method. The compound 2 had the highest activity against Helicobacter pylori (MIC 3.9 microg/mL). Its chemical structure was elucidated as quercetin 3-methyl ether (isorhamnetin) by various spectroscopic techniques. We believe that the therapeutic effect of Cistus laurifolius in ulcer is at least partially related to its effect on Helicobacter pylori. We hope that the isolated flavonoid having anti-Helicobacter pylori activity ultimately can be utilized as an alternative or additive agent to the current therapy.
J Lang, Ben; J Gorrell, Rebecca; Tafreshi, Mona; Hatakeyama, Masanori; Kwok, Terry; T Price, John
Bacterial infections typically elicit a strong Heat Shock Response (HSR) in host cells. However, the gastric pathogen Helicobacter pylori has the unique ability to repress this response, the mechanism of which has yet to be elucidated. This study sought to characterize the underlying mechanisms by which H. pylori down-modulates host HSP expression upon infection. Examination of isogenic mutant strains of H. pylori defective in components of the type IV secretion system (T4SS), identified the secretion substrate, CagA, to be essential for down-modulation of the HSPs HSPH1 (HSP105), HSPA1A (HSP72), and HSPD1 (HSP60) upon infection of the AGS gastric adenocarcinoma cell line. Ectopic expression of CagA by transient transfection was insufficient to repress HSP expression in AGS or HEK293T cells, suggesting that additional H. pylori factors are required for HSP repression. RT-qPCR analysis of HSP gene expression in AGS cells infected with wild-type H. pylori or isogenic cagA-deletion mutant found no significant change to account for reduced HSP levels. In summary, this study identified CagA to be an essential bacterial factor for H. pylori-mediated suppression of host HSP expression. The novel finding that HSPH1 is down-modulated by H. pylori further highlights the unique ability of H. pylori to repress the HSR within host cells. Elucidation of the mechanism by which H. pylori achieves HSP repression may prove to be beneficial in the identification of novel mechanisms to inhibit the HSR pathway and provide further insight into the interactions between H. pylori and the host gastric epithelium.
Ierardi, Enzo; Goni, Elisabetta; Losurdo, Giuseppe; Di Mario, Francesco
Peptic ulcer bleeding and recurrence rate are strongly linked to Helicobacter pylori infection even if nonsteroidal anti-inflammatory drugs (NSAIDs) play a relevant role in this setting. Further studies confirm that H. pylori eradication lowers the risk of recurrent peptic ulcer bleeding. Therefore, a test-and-treat strategy appears to be mandatory for patients with a history of ulcer bleeding and NSAIDs and/or aspirin use. Concerning gastroesophageal reflux disease (GERD), evidence clearly shows that H. pylori status has no effect on symptoms and treatment. Therefore, H. pylori treatment is not contraindicated in patients with GERD. The exact role of H. pylori in functional dyspepsia (FD) remains controversial. Novel possible mechanisms by which H. pylori may elicit dyspeptic symptoms include alterations of gastric motility, as well as endocrine and acid-secretory abnormalities. Hunger sensations, acid secretion, and gastrointestinal motility are regulated by ghrelin, particularly produced by the gastric enteroendocrine cell compartment. The improvement of symptoms correlates with enhanced plasma ghrelin levels. Apart from the need for more trials on this topic, these findings may give insight into the underlying pathophysiology of FD symptoms. Recent reports suggest that the presence of bacterial DNA in the oral cavity may be relevant to its transmission. A potential protective role of H. pylori on inflammatory bowel diseases needs to be better elucidated.
Kalach, Nicolas; Bontems, Patrick; Raymond, Josette
Helicobacter pylori infection in children differs from that in adults, from the point of view of epidemiology, host response, clinical features, related diseases, and diagnosis, as well as treatment strategies. The prevalence of H. pylori infection, in both children and adults, is decreasing in the Western World as well as in some developing countries, which contrasts with the increase in childhood asthma and allergic diseases. Recurrent abdominal pain is not specific during H. pylori infection in children. The role of H. pylori infection and failure to thrive, children's growth, type I diabetes mellitus (T1DM) and celiac disease remains controversial. The main initial diagnosis is based on upper digestive endoscopy with biopsy-based methods. Nodular gastritis may be a pathognomonic endoscopic finding of childhood H. pylori infection. The infection eradication control is based on validated noninvasive tests. The main cause of treatment failure of H. pylori infection is its clarithromycin resistance. We recommend standard antibiotic susceptibility testing of H. pylori in pediatric patients prior to the initiation of eradication therapy. H. pylori treatment in children should be based on an evaluation of the rate of eradication in the local population, a systematic use of a treatment adapted to the susceptibility profile and a treatment compliance greater than 90%. The last meta-analysis in children did not show an advantage for sequential therapy when compared to a 14-day triple therapy. Finally, the high rate of antibiotic resistance responsible for therapy failure in recent years justifies the necessity of a novel vaccine to prevent H. pylori infection in children. © 2017 John Wiley & Sons Ltd.
Batioglu-Karaaltin, Aysegul; Saatci, Ozlem; Akpinar, Meltem; Celik, Melih Ozgür; Develioglu, Omer; Yigit, Ozgur; Külekçi, Mehmet; Akarsubaşı, Alper Tunga
The aim of this study was to investigate the presence of Helicobacter pylori in human lacrimal and nasal secretions. Eighty patients with complaints of dyspepsia who had undergone endoscopies and gastric antrum biopsies were included in the study. A total of five specimens, including 2 lacrimal secretion samples, 2 nasal mucosal swab samples, and 1 gastric antrum biopsy, were collected from each patient and investigated with polymerase chain reaction (PCR) methods consisting of the urease enzyme coding gene GlmM (UreC) and the H pylori-specific 16S rRNA coding gene. The Reflux Symptom Index and ophthalmologic complaints of the patients were recorded. The detected positivity rates of the H pylori 16S rRNA coding gene in gastric biopsies and nasal mucous and lacrimal secretions were 55, 11.2, and 20%, respectively. The patients were grouped as gastric-antrum-biopsy-negative (Group I [n = 36]) and -positive (Group II [n = 44). In Group II, H pylori positivity in the lacrimal and nasal mucous secretions was 36.3 and 18%, respectively. A comparison between the groups in terms of H pylori presence in nasal mucous and lacrimal secretions yielded statistically significant differences (p = 0.0001, p = 0.003). The simultaneous presence of H pylori in nasal mucous and lacrimal secretions was 13.6% in Group II. H pylori positivity in nasal mucous and lacrimal secretions had a positive moderate correlation (r = 0.40; p = 0.0003). The present study is the first report on the presence of H pylori in lacrimal secretions through nested PCR, which suggested the presence of a number of mechanisms for H pylori transmission to lacrimal secretions.
Tytgat, G N
The contamination of endoscopes and biopsy forceps with Helicobacter pylori occurs readily after endoscopic examination of H. pylori-positive patients. Unequivocal proof of iatrogenic transmission of the organism has been provided. Estimates for transmission frequency approximate to 4 per 1000 endoscopies when the infection rate in the endoscoped population is about 60%. Iatrogenic transmission has also been shown to be the cause of the so-called 'acute mucosal lesion' syndrome in Japan. Traditional cleaning and alcohol rinsing is insufficient to eliminate endoscope/forceps contamination. Only meticulous adherence to disinfection recommendations guarantees H. pylori elimination.
Mnich, Eliza; Kowalewicz-Kulbat, Magdalena; Sicińska, Paulina; Hinc, Krzysztof; Obuchowski, Michał; Gajewski, Adrian; Moran, Anthony P; Chmiela, Magdalena
To determine the impact of selected well defined Helicobacter pylori (H. pylori) antigens on gastric barrier cell turnover. In this study, using two cellular models of gastric epithelial cells and fibroblasts, we have focused on exploring the effects of well defined H. pylori soluble components such as glycine acid extract antigenic complex (GE), subunit A of urease (UreA), cytotoxin associated gene A protein (CagA) and lipopolysaccharide (LPS) on cell turnover by comparing the wound healing capacity of the cells in terms of their proliferative and metabolic activity as well as cell cycle distribution. Toxic effects of H. pylori components have been assessed in an association with damage to cell nuclei and inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation. We showed that H. pylori GE, CagA and UreA promoted regeneration of epithelial cells and fibroblasts, which is necessary for effective tissue healing. However, in vivo increased proliferative activity of these cells may constitute an increased risk of gastric neoplasia. In contrast, H. pylori LPS showed a dose-dependent influence on the process of wound healing. At a low concentration (1 ng/mL) H. pylori LPS accelerated of healing epithelial cells, which was linked to significantly enhanced cell proliferation and MTT reduction as well as lack of alterations in cell cycle and downregulation of epidermal growth factor (EGF) production as well as cell nuclei destruction. By comparison, H. pylori LPS at a high concentration (25 ng/mL) inhibited the process of wound repair, which was related to diminished proliferative activity of the cells, cell cycle arrest, destruction of cell nuclei and downregulation of the EGF/STAT3 signalling pathway. In vivo H. pylori LPS driven effects might lead to the maintenance of chronic inflammatory response and pathological disorders on the level of the gastric mucosal barrier.
Mnich, Eliza; Kowalewicz-Kulbat, Magdalena; Sicińska, Paulina; Hinc, Krzysztof; Obuchowski, Michał; Gajewski, Adrian; Moran, Anthony P; Chmiela, Magdalena
AIM To determine the impact of selected well defined Helicobacter pylori (H. pylori) antigens on gastric barrier cell turnover. METHODS In this study, using two cellular models of gastric epithelial cells and fibroblasts, we have focused on exploring the effects of well defined H. pylori soluble components such as glycine acid extract antigenic complex (GE), subunit A of urease (UreA), cytotoxin associated gene A protein (CagA) and lipopolysaccharide (LPS) on cell turnover by comparing the wound healing capacity of the cells in terms of their proliferative and metabolic activity as well as cell cycle distribution. Toxic effects of H. pylori components have been assessed in an association with damage to cell nuclei and inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation. RESULTS We showed that H. pylori GE, CagA and UreA promoted regeneration of epithelial cells and fibroblasts, which is necessary for effective tissue healing. However, in vivo increased proliferative activity of these cells may constitute an increased risk of gastric neoplasia. In contrast, H. pylori LPS showed a dose-dependent influence on the process of wound healing. At a low concentration (1 ng/mL) H. pylori LPS accelerated of healing epithelial cells, which was linked to significantly enhanced cell proliferation and MTT reduction as well as lack of alterations in cell cycle and downregulation of epidermal growth factor (EGF) production as well as cell nuclei destruction. By comparison, H. pylori LPS at a high concentration (25 ng/mL) inhibited the process of wound repair, which was related to diminished proliferative activity of the cells, cell cycle arrest, destruction of cell nuclei and downregulation of the EGF/STAT3 signalling pathway. CONCLUSION In vivo H. pylori LPS driven effects might lead to the maintenance of chronic inflammatory response and pathological disorders on the level of the gastric mucosal barrier. PMID:27672275
Celli, Jonathan P.; Turner, Bradley S.; Afdhal, Nezam H.; Keates, Sarah; Ghiran, Ionita; Kelly, Ciaran P.; Ewoldt, Randy H.; McKinley, Gareth H.; So, Peter; Erramilli, Shyamsunder; Bansil, Rama
The ulcer-causing gastric pathogen Helicobacter pylori is the only bacterium known to colonize the harsh acidic environment of the human stomach. H. pylori survives in acidic conditions by producing urease, which catalyzes hydrolysis of urea to yield ammonia thus elevating the pH of its environment. However, the manner in which H. pylori is able to swim through the viscoelastic mucus gel that coats the stomach wall remains poorly understood. Previous rheology studies on gastric mucin, the key viscoelastic component of gastric mucus, indicate that the rheology of this material is pH dependent, transitioning from a viscous solution at neutral pH to a gel in acidic conditions. Bulk rheology measurements on porcine gastric mucin (PGM) show that pH elevation by H. pylori induces a dramatic decrease in viscoelastic moduli. Microscopy studies of the motility of H. pylori in gastric mucin at acidic and neutral pH in the absence of urea show that the bacteria swim freely at high pH, and are strongly constrained at low pH. By using two-photon fluorescence microscopy to image the bacterial motility in an initially low pH mucin gel with urea present we show that the gain of translational motility by bacteria is directly correlated with a rise in pH indicated by 2′,7′-Bis-(2-Carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF), a pH sensitive fluorescent dye. This study indicates that the helicoidal-shaped H. pylori does not bore its way through the mucus gel like a screw through a cork as has previously been suggested, but instead achieves motility by altering the rheological properties of its environment. PMID:19706518
Ogden, Seth R.; Wroblewski, Lydia E.; Weydig, Christiane; Romero-Gallo, Judith; O'Brien, Daniel P.; Israel, Dawn A.; Krishna, Uma S.; Fingleton, Barbara; Reynolds, Albert B.; Wessler, Silja
Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, yet only a fraction of infected persons develop cancer. One H. pylori constituent that augments disease risk is the cytotoxin-associated gene (cag) pathogenicity island, which encodes a secretion system that translocates bacterial effector molecules into host cells. Matrix metalloproteinase (MMP)-7, a member of a family of enzymes with tumor-initiating properties, is overexpressed in premalignant and malignant gastric lesions, and H. pylori cag+ strains selectively increase MMP-7 protein levels in gastric epithelial cells in vitro and in vivo. We now report that H. pylori-mediated mmp-7 induction is transcriptionally regulated via aberrant activation of p120-catenin (p120), a component of adherens junctions. H. pylori increases mmp-7 mRNA levels in a cag- and p120-dependent manner and induces translocation of p120 to the nucleus in vitro and in a novel ex vivo gastric gland culture system. Nuclear translocation of p120 in response to H. pylori relieves Kaiso-mediated transcriptional repression of mmp-7, which is implicated in tumorigenesis. These results indicate that selective and coordinated induction of mmp-7 expression by H. pylori cag+ isolates may explain in part the augmentation in gastric cancer risk associated with these strains. PMID:18653469
Kountouras, Jannis; Gavalas, Emmanuel; Zavos, Christos; Stergiopoulos, Christos; Chatzopoulos, Dimitrios; Kapetanakis, Nikolaos; Gisakis, Dimitrios
Although degenerative diseases of the central nervous system, including Alzheimer's disease (AD), have an increasingly high impact on aged population their association with Helicobacter pylori (H. pylori) infection has not as yet been thoroughly researched. Current H. pylori infection appears to induce irregular humoral and cellular immune responses that, owing to the sharing of homologous epitopes (molecular mimicry), cross-react with components of nerves, thereby contributing and possibly perpetuating the apoptotic neural tissue damage observed in neurodegenerative diseases including AD. An association between AD and H. pylori infection has been recently addressed by two studies. A higher seropositivity for anti-H. pylori immunoglobulin G antibodies in 30 patients with AD than in 30 age-matched controls was reported in one study; this serological test, however, has limitations because it does not discriminate between current and old infections. In the other study, by introducing the histological method (the actual gold standard) for diagnosis of H. pylori infection, we reported a higher prevalence of H. pylori infection in 50 AD patients than in 30 anemic controls. This pathogen may influence the pathophysiology of AD by promoting platelet and platelet-leukocyte aggregation; releasing various pro-inflammatory and vasoactive substances; developing cross-mimicry with host antigens; producing reactive oxygen metabolites and circulating lipid peroxides; influencing the apoptotic process; and increasing, through induction of atrophic gastritis, homocysteine, which contributes to vascular disorders implicated in endothelial damage and neurodegeneration.
Buzás, György Miklós
The author reviews the main achievements in Helicobacter pylori research in the past 2 years. Of the more than 1000 microRNAs described thus far, sets of over- and underexpressed samples were identified that are associated with either gastric cancer or precancerous lesions, and some of them could be either markers or therapeutic targets in the near future. Meta-analyses involved 95 new publications: the association between infection and oesophageal, colorectal, pancreatic and liver carcinomas is supported by the increased odds ratios, but the results do not reach the strength seen in gastric carcinoma. Epstein-Barr virus is an emerging pathogen: 10% of gastric cancers are virus-associated; the prevalence of the virus in normal mucosa, chronic gastritis and peptic ulcer are currently being studied. Current Helicobacter pylori eradication regimens frequently achieve suboptimal results: a few optimisation methods are presented, although not all are supported by the meta-analyses. In 2013, the European Helicobacter Study Group proposed the development of a pan-European registry; data from 5792 patients registered so far indicated that many therapeutic regimens resulted in a low eradication rate. In 2013, the Healthy Stomach Initiative was started with the aim of supporting and disseminating research performed in the field of healthy and diseased stomachs.
Scott, David R.
Helicobacter pylori infects about 50% of the world’s population and inevitably results in the development of gastritis. Of those infected, about 10% develop peptic ulcer disease and roughly 1% develop gastric cancer. Conversely, some take the view that H. pylori infection provides some protection against gastro-esophageal reflux disease and possibly asthma. This review aims to explore the case for and against eradication of the bacterium using a “test and treat” approach amongst the general population. PMID:22500191
Nemati, Maryam; Larussa, Tiziana; Khorramdelazad, Hossein; Mahmoodi, Merat; Jafarzadeh, Abdollah
Toll like receptors (TLRs) are an essential subset of pathogen recognition receptors (PRRs) which identify the microbial components and contribute in the regulation of innate and adaptive immune responses against the infectious agents. The TLRs, especially TLR2, TLR4, TLR5 and TLR9, participate in the induction of immune response against H. pylori. TLR2 is expressed on a number of immune and non-immune cells and recognizes a vast broad of microbial components due to its potential to form heterodimers with other TLRs, including TLR1, TLR6 and TLR10. A number of H. pylori-related molecules may contribute to TLR2-dependent responses, including HP-LPS, HP-HSP60 and HP-NAP. TLR2 plays a pivotal role in regulation of immune response to H. pylori through activation of NF-κB and induction of cytokine expression in epithelial cells, monocytes/macrophages, dendritic cells, neutrophils and B cells. The TLR2-related immune response that is induced by H. pylori-derived components may play an important role regarding the outcome of the infection toward bacterial elimination, persistence or pathological reactions. The immunomodulatory and immunoregulatory roles of TLR2 during H. pylori infection were considered in this review. TLR2 could be considered as an interesting therapeutic target for treatment of H. pylori-related diseases. Copyright © 2017 Elsevier Inc. All rights reserved.
Sgouras, Dionyssios N.; Trang, Tran Thi Huyen; Yamaoka, Yoshio
Three decades have passed since Warren and Marshall described the successful isolation and culture of Helicobacter pylori, the Gram-negative bacterium that colonizes the stomach of half the human population worldwide. Although it is documented that H. pylori infection is implicated in a range of disorders of the upper gastrointestinal tract, as well as associated organs, many aspects relating to host colonization, successful persistence and the pathophysiological mechanisms of this bacteria still remain controversial and are constantly being explored. Unceasing efforts to decipher the pathophysiology of H. pylori infection have illuminated the crucially important contribution of multifarious bacterial factors for H. pylori pathogenesis, in particular the cag pathogenicity island (PAI), the effector protein CagA and the vacuolating cytotoxin VacA. In addition, recent studies have provided insight into the importance of the gastrointestinal microbiota on the cumulative pathophysiology associated with H. pylori infections. This review focuses on the key findings of publications related to the pathogenesis of H. pylori infection published during the last year, with an emphasis on factors affecting colonization efficiency, cag PAI, CagA, VacA and gastrointestinal microbiota. PMID:26372819
Sgouras, Dionyssios N; Trang, Tran Thi Huyen; Yamaoka, Yoshio
Three decades have passed since Warren and Marshall described the successful isolation and culture of Helicobacter pylori, the Gram-negative bacterium that colonizes the stomach of half the human population worldwide. Although it is documented that H. pylori infection is implicated in a range of disorders of the upper gastrointestinal tract, as well as associated organs, many aspects relating to host colonization, successful persistence, and the pathophysiological mechanisms of this bacteria still remain controversial and are constantly being explored. Unceasing efforts to decipher the pathophysiology of H. pylori infection have illuminated the crucially important contribution of multifarious bacterial factors for H. pylori pathogenesis, in particular the cag pathogenicity island (PAI), the effector protein CagA, and the vacuolating cytotoxin VacA. In addition, recent studies have provided insight into the importance of the gastrointestinal microbiota on the cumulative pathophysiology associated with H. pylori infection. This review focuses on the key findings of publications related to the pathogenesis of H. pylori infection published during the last year, with an emphasis on factors affecting colonization efficiency, cagPAI, CagA, VacA, and gastrointestinal microbiota. © 2015 John Wiley & Sons Ltd.
Hasni, S; Ippolito, A; Illei, GG
Helicobacter pylori (H. pylori) is a widely prevalent microbe, with between 50 and 80% of the population infected worldwide. Clinically, infection with H. pylori is commonly associated with peptic ulcer disease, but many of those infected remain asymptomatic. H. pylori has evolved a number of means to affect the host immune response and has been implicated in many diseases mitigated by immune dysregulation, such as immune thrombocytopenic purpura (ITP), atrophic gastritis, and mucosa associated lymphoid tissue (MALT) lymphoma. Autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Sjogren’s syndrome, are the result of a dysregulated host immune system which targets otherwise healthy tissues. The exact etiology of autoimmune diseases is unclear, but it has long been suggested that exposure to certain environmental agents, such as viral and bacterial infection or chemical exposures, in genetically susceptible individuals may be the catalyst for the initiation of autoimmune processes. Because of its prevalence and ability to affect human immune function, many researchers have hypothesized that H. pylori might contribute to the development of autoimmune diseases. In this article, we review the available literature regarding the role of chronic H. pylori infection in various autoimmune disease states. PMID:21902767
Vartanova, N O; Arzumanyan, V G; Serdyuk, O A; Temper, R M
We developed a scheme of consecutive replacement of complex components of a known Brucella medium containing peptones and blood with simple analogs and created a synthetic medium for Helicobacter pylori culturing. H. pylori cells require hemic iron for their growth; an appreciable increment in biomass was ensured by hemoglobin, but not simpler hemocontaining compounds (hemin and cytochrome C). Glutamine (20 g/liter) was used as the main nitrogen-containing component, and other amino acids were added in trace amounts. Adhesion was provided by adding agarose gel (0.1%) also promoting the increase in biomass. The proposed medium of a certain chemical composition differs from the known foreign analogs by the presence of hemocontaining component (hemoglobin), short period of exponential growth, and appreciable accumulation of cell protein.
Shmuely, Haim; Domniz, Noam; Yahav, Jacob
Many food and plant extracts have shown in vitro anti-Helicobacter pylori (H. pylori) activity, but are less effective in vivo. The anti-H. pylori effects of these extracts are mainly permeabilitization of the membrane, anti-adhesion, inhibition of bacterial enzymes and bacterial grown. We, herein, review treatment effects of cranberry, garlic, curcumin, ginger and pistacia gum against H. pylori in both in vitro, animal studies and in vivo studies. PMID:27158532
Infection with Helicobacter pylori affects 20-40% of the adult population in advanced countries. A causal relationship between Helicobacter pylori and gastritis type B was proved. There is some indirect conclusive evidence of an aetiological association with peptic gastroduodenal ulceration. Attention is drawn to possible associations with gastric malignities. The author reviews aetiopathogenetic relations between Helicobacter pylori infection and these diseases.
Mukaisho, Ken-ichi; Hagiwara, Tadashi; Nakayama, Takahisa; Hattori, Takanori; Sugihara, Hiroyuki
The long-term use of proton pump inhibitors (PPIs) exacerbates corpus atrophic gastritis in patients with Helicobacter pylori (H. pylori) infection. To identify a potential mechanism for this change, we discuss interactions between pH, bile acids, and H. pylori. Duodenogastric reflux, which includes bile, occurs in healthy individuals, and bile reflux is increased in patients with gastroesophageal reflux disease (GERD). Diluted human plasma and bile acids have been found to be significant chemoattractants and chemorepellents, respectively, for the bacillus H. pylori. Although only taurine conjugates, with a pKa of 1.8-1.9, are soluble in an acidic environment, glycine conjugates, with a pKa of 4.3-5.2, as well as taurine-conjugated bile acids are soluble in the presence of PPI therapy. Thus, the soluble bile acid concentrations in the gastric contents of patients with GERD after continuous PPI therapy are considerably higher than that in those with intact acid production. In the distal stomach, the high concentration of soluble bile acids is likely to act as a bactericide or chemorepellent for H. pylori. In contrast, the mucous layer in the proximal stomach has an optimal bile concentration that forms chemotactic gradients with plasma components required to direct H. pylori to the epithelial surface. H. pylori may then colonize in the stomach body rather than in the pyloric antrum, which may explain the occurrence of corpus-predominant gastritis after PPI therapy in H. pylori-positive patients with GERD.
Introduction Oral sex (fellatio) is a very common sexual activity. H. pylori is mainly a gastric organism, but studies have reported that infected individuals may permanently or transiently carry H. pylori in their mouth and saliva. Material and methods A Pubmed search was conducted using the words infection, oral sex and urethritis. Results The existing studies support the hypothesis that H. pylori could be a causative agent of non–gonococcal urethritis. Conclusions It is possible that H. pylori may be transmitted via the act of fellatio in the urethra. Further research is required to explore the role of H. pylori in sexually transmitted urethritis. PMID:25667764
Alba, Claudio; Blanco, Ana; Alarcón, Teresa
Treatment of Helicobacter pylori is difficult nowadays because of its high resistance. The prevalence and mechanism of resistance, the different methods to detect it and the clinical implication of resistance were addressed in several research papers last year. Clarithromycin-resistant H. pylori has been recognized by the WHO as 'high priority', for which new antibiotics are needed. Moreover, the Maastricht consensus recommended, in areas with high resistance, that susceptibility tests should be performed, at least after a treatment failure. Metronidazole and clarithromycin resistance rates are alarming although they vary among populations. Tetracycline and amoxicillin-resistance are very low in most countries. H. pylori resistance can be detected by phenotypic or by molecular methods. Different break points may be used when performing an antimicrobial susceptibility test, so comparing resistance among different populations is challenging. Genomic techniques open new possibilities in the diagnosis of H. pylori, and the detection of H. pylori and its antimicrobial resistance in faeces is an interesting approach. Eradication rates are dependent on the susceptibility of the strain to metronidazole and clarithromycin, being lower in patients infected with a resistant strain.
Rautelin, Hilpi; Kosunen, Timo U
Helicobacter pylori causes chronic gastritis worldwide and it is the most important single factor in peptic ulcer disease. Up to half of H. pylori infected individuals develop atrophic gastritis over years and decades. H. pylori infection has also been classified as a class I carcinogen in human gastric cancer. Most infections are obtained in childhood, in Finland mainly before the age of 7 years but the exact transmission routes are not known. The infection shows an age-dependent pattern, the infection being rare among children but gradually becoming more prevalent among older age groups. As new infections are few in adults and the infection only rarely disappears without effective anti-microbial therapy, the occurrence of the infection in the old actually reflects the prevalence of the infection in their childhood. In developed countries, such as Finland, a rapid decline of H. pylori prevalence rate has been demonstrated. In order to speed up this natural decline of the infection, a unique population based 'screen and treat' project was started in Vammala, a semiurban south-western community in Finland. In this survey, young inhabitants were offered diagnosis and treatment for H. pylori.
Leja, Mārcis; Axon, Anthony; Brenner, Hermann
This review of recent publications related to the epidemiology of Helicobacter pylori highlights the origin of the infection, its changing prevalence, transmission, and outcome. A number of studies have addressed the ancestor roots of the bacteria, and the first genomewide analysis of bacterial strains suggests that its coexistence with humans is more ancient than previously thought. As opposed to the generally declining prevalence of H. pylori (including China and Japan), in Sweden, the prevalence of atrophic gastritis in the young population has risen. The prevalence of the infection remains high in the indigenous populations of the Arctic regions, and reinfection rates are high. A high prevalence is permanently found in the Siberian regions of Russia as well. Several studies, some of which used multiplex serology, addressed prevalence of and risks associated with various H. pylori serotypes, thereby enabling more precise risk assessment. Transmission of H. pylori was discussed, specifically fecal-oral transmission and the use of well-water and other unpurified water. Finally, the long-term course of H. pylori infection was considered, with an estimated 89% of noncardia gastric cancer cases being attributable to the infection.
Kutlubay, Zekayi; Zara, Tuba; Engin, Burhan; Serdaroğlu, Server; Tüzün, Yalçin; Yilmaz, Erkan; Eren, Bülent
Helicobacter pylori is a Gram-negative bacterium that has been linked to peptic ulcer disease, gastric lymphoma, and gastric carcinoma. Apart from its well-demonstrated role in gastroduodenal diseases, some authors have suggested a potential role of Helicobacter pylori infection in several extra-intestinal pathologies including haematological, cardiovascular, neurological, metabolic, autoimmune, and dermatological diseases. Some studies suggest an association between Helicobacter pylori infection and skin diseases such as chronic idiopathic urticaria and rosacea. There have also been few case reports documenting association between Helicobacter pylori and psoriasis vulgaris, Behçet's disease, alopecia areata, Henoch-Schönlein purpura, and Sweet's syndrome. However, more systematic studies are required to clarify the proposed association between Helicobacter pylori and skin diseases; most of the studies do not show relevant relationships of these diseases with Helicobacter pylori infections. This review discusses skin diseases that are believed to be associated with Helicobacter pylori.
Helicobacter pylori infection has accompanied man for thousands of years. In some infected patients, a complex and dynamic pathogen-host reaction triggers pathogenic pathways resulting in development, inter alia, of atrophic gastritis, peptic ulcer disease (both gastric and duodenal), gastric adenocarcinoma, and MALT lymphoma. Large-scale eradication therapy is associated with a rapid increase in antibiotic resistance, gut flora composition disturbances, and increased risk of development, inter alia, of paediatric infectious diarrhoeas, atopic diseases, and oesophageal adenocarcinoma. Our diet contains many substances with potent antibacterial activity against H. pylori. Dietary interventions enable a decrease in H. pylori colonisation and result in a decrease in gastritis prevalence, thus potentially lowering the risk of gastric adenocarcinoma development. PMID:27713775
Yılmaz, Taner; Bajin, Münir Demir; Günaydın, Rıza Önder; Özer, Serdar; Sözen, Tevfik
Laryngopharyngeal reflux (LPR) occurs when gastric contents pass the upper esophageal sphincter, causing symptoms such as hoarseness, sore throat, coughing, excess throat mucus, and globus. The pattern of reflux is different in LPR and gastroesophageal reflux. LPR usually occurs during the daytime in the upright position whereas gastroesophageal reflux disease more often occurs in the supine position at night-time or during sleep. Ambulatory 24-h double pH-probe monitoring is the gold standard diagnostic tool for LPR. Acid suppression with proton pump inhibitor on a long-term basis is the mainstay of treatment. Helicobacter pylori (H. pylori) is found in many sites including laryngeal mucosa and interarytenoid region. In this paper, we aim to present the relationship between LPR and H. pylori and review the current literature. PMID:25083069
Longo-Mbenza, B; Nkondi Nsenga, J; Vangu Ngoma, D
To report on the association between certain components of the metabolic syndrome/Insulin resistance, gender, cardiovascular diseases and Helicobacter (H.) pylori seropositivity/Infection and the response of these cardiovascular risk factors to Helicobacter pylori titers after an antibiotic course. In 205 consecutive Africans referred to the cardiovascular Center of LOMO MEDICAL in Kinshasa for management of their cardiovascular diseases, the proportions of seropositives for H. pylori and H. pylori infection (H. pylori seropositivity and histologically proven H. pylori gastritis) were investigated. The association between traditional cardiovascular risk factors, certain components of the metabolic syndrome and each H. pylori disease group (seropositivity or infection) was evaluated. The response of the cardio-metabolic level to H. pylori antibody titers after an antibiotic course was also evaluated for patients with H. pylori infection. Baseline levels of H. pylori antibody titer and cardio-metabolic parameters were compared with those after the antibiotic treatment. A total of 62.4% of participants were tested positive for the H. pylori antibody. Out of all participants, 25% had H. pylori infection and chronic gastritis without H. pylori. Men were more (p<0.01) H. pylori seropositive than women. Older age, higher triglycerides, higher weight, wider waist girth, higher fibrinogenemia, greater intima-mediathighness and higher rate of hypertension were significantly associated with H. pylori seropositivity. Lower HDL-cholesterol, higher levels of systolic blood pressure, triglycerides, uric acid, fibrinogen, hematocrit, glycemia, arterial hypertension hypercholesterolemia, diabetes mellitus hypo-HDL-cholesterolemia, hyperuricemia (Total), Overweight, overall obesity, abdominal obesity were significantly associated with H. pylori infection. Within the total population, there was a significant dose-response relationship between the rates of arterial hypertension, rate
Noto, Jennifer M.; Peek, Richard M.
Genetic manipulation of Helicobacter pylori facilitates characterization and functional analysis of individual H. pylori genes. This chapter discusses the methods involved in H. pylori chromosomal DNA isolation, mutagenesis of individual genes, and natural transformation. PMID:23015491
Kyburz, A; Urban, S; Altobelli, A; Floess, S; Huehn, J; Cover, T L; Müller, A
Food allergy is an increasingly common health problem in Western populations. Epidemiological studies have suggested both positive and negative associations between food allergy and infection with the gastric bacterium Helicobacter pylori. The objective of this work was to investigate whether experimental infection with H. pylori, or prophylactic treatment with H. pylori-derived immunomodulatory molecules, affects the onset and severity of food allergy, either positively or negatively. We infected neonatal C57BL/6 or C3H mice with H. pylori or treated animals with H. pylori components (bacterial lysate or the immunomodulator VacA) and subsequently subjected them to four different protocols for food allergy induction, using either ovalbumin or peanut extract as allergens for sensitization and challenge. Readouts included anaphylaxis scoring, quantification of allergen-specific serum IgE and IgG1 and of the mast cell protease MCPT1, as well as splenic T-helper-2 cell-derived cytokine production. Mesenteric lymph node CD4(+) FoxP3(+) regulatory T cells were subjected to flow cytometric quantification and sorting followed by qRT-PCR, and to DNA methylation analyses of the Treg-specific demethylated region (TSDR) within the FOXP3 locus. Mice that had been infected with H. pylori or treated with H. pylori-derived immunomodulators showed reduced anaphylaxis upon allergen sensitization and challenge, irrespective of the allergen used. Most of the immunologic assays confirmed a protective effect of H. pylori. CD4(+) FoxP3(+) T cells were more abundant in protected mice and exhibited a stable Treg phenotype characterized by FOXP3 TSDR demethylation. Helicobacter pylori confers protection against the anaphylaxis associated with ovalbumin and peanut allergy and affects the epigenome of T cells, thereby promoting stable Treg differentiation and functionality. Prophylactic treatment with H. pylori-derived immunomodulators appears to be a promising strategy for food allergy
Hug, Isabelle; Couturier, Marc R; Rooker, Michelle M; Taylor, Diane E; Stein, Markus; Feldman, Mario F
Lipopolysaccharide (LPS) is a major component on the surface of Gram negative bacteria and is composed of lipid A-core and the O antigen polysaccharide. O polysaccharides of the gastric pathogen Helicobacter pylori contain Lewis antigens, mimicking glycan structures produced by human cells. The interaction of Lewis antigens with human dendritic cells induces a modulation of the immune response, contributing to the H. pylori virulence. The amount and position of Lewis antigens in the LPS varies among H. pylori isolates, indicating an adaptation to the host. In contrast to most bacteria, the genes for H. pylori O antigen biosynthesis are spread throughout the chromosome, which likely contributed to the fact that the LPS assembly pathway remained uncharacterized. In this study, two enzymes typically involved in LPS biosynthesis were found encoded in the H. pylori genome; the initiating glycosyltransferase WecA, and the O antigen ligase WaaL. Fluorescence microscopy and analysis of LPS from H. pylori mutants revealed that WecA and WaaL are involved in LPS production. Activity of WecA was additionally demonstrated with complementation experiments in Escherichia coli. WaaL ligase activity was shown in vitro. Analysis of the H. pylori genome failed to detect a flippase typically involved in O antigen synthesis. Instead, we identified a homolog of a flippase involved in protein N-glycosylation in other bacteria, although this pathway is not present in H. pylori. This flippase named Wzk was essential for O antigen display in H. pylori and was able to transport various glycans in E. coli. Whereas the O antigen mutants showed normal swimming motility and injection of the toxin CagA into host cells, the uptake of DNA seemed to be affected. We conclude that H. pylori uses a novel LPS biosynthetic pathway, evolutionarily connected to bacterial protein N-glycosylation.
Wang, Xiu-Lian; Zeng, Ji; Feng, Jin; Tian, Yi-Tao; Liu, Yu-Jian; Qiu, Mei; Yan, Xiong; Yang, Yang; Xiong, Yan; Zhang, Zhi-Hua; Wang, Qun; Wang, Jian-Zhi; Liu, Rong
Helicobacter pylori (H. pylori) infection is related with a high risk of Alzheimer's disease (AD), but the intrinsic link between H. pylori infection and AD development is still missing. In the present study, we explored the effect of H. pylori infection on cognitive function and β-amyloid production in rats. We found that intraperitoneal injection of H. pylori filtrate induced spatial learning and memory deficit in rats with a simultaneous retarded dendritic spine maturation in hippocampus. Injection of H. pylori filtrate significantly increased Aβ42 both in the hippocampus and cortex, together with an increased level of presenilin-2 (PS-2), one key component of γ-secretase involved in Aβ production. Incubation of H. pylori filtrate with N2a cells which over-express amyloid precursor protein (APP) also resulted in increased PS-2 expression and Aβ42 overproduction. Injection of Escherichia coli (E.coli) filtrate, another common intestinal bacterium, had no effect on cognitive function in rats and Aβ production in rats and cells. These data suggest a specific effect of H. pylori on cognition and Aβ production. We conclude that soluble surface fractions of H. pylori may promote Aβ42 formation by enhancing the activity of γ-secretase, thus induce cognitive impairment through interrupting the synaptic function.
Wang, Xiu-Lian; Zeng, Ji; Feng, Jin; Tian, Yi-Tao; Liu, Yu-Jian; Qiu, Mei; Yan, Xiong; Yang, Yang; Xiong, Yan; Zhang, Zhi-Hua; Wang, Qun; Wang, Jian-Zhi; Liu, Rong
Helicobacter pylori (H. pylori) infection is related with a high risk of Alzheimer's disease (AD), but the intrinsic link between H. pylori infection and AD development is still missing. In the present study, we explored the effect of H. pylori infection on cognitive function and β-amyloid production in rats. We found that intraperitoneal injection of H. pylori filtrate induced spatial learning and memory deficit in rats with a simultaneous retarded dendritic spine maturation in hippocampus. Injection of H. pylori filtrate significantly increased Aβ42 both in the hippocampus and cortex, together with an increased level of presenilin-2 (PS-2), one key component of γ-secretase involved in Aβ production. Incubation of H. pylori filtrate with N2a cells which over-express amyloid precursor protein (APP) also resulted in increased PS-2 expression and Aβ42 overproduction. Injection of Escherichia coli (E.coli) filtrate, another common intestinal bacterium, had no effect on cognitive function in rats and Aβ production in rats and cells. These data suggest a specific effect of H. pylori on cognition and Aβ production. We conclude that soluble surface fractions of H. pylori may promote Aβ42 formation by enhancing the activity of γ-secretase, thus induce cognitive impairment through interrupting the synaptic function. PMID:24782763
Gisbert, Javier P
This article summarizes the main conclusions drawn from the presentations on Helicobacter pylori at Digestive Disease Week 2013. Knowledge of this infection among the general population continues to be extremely limited. H. pylori is the main cause of "aging" of the human stomach. In developed countries, the prevalence of H. pylori infection has decreased but continues to be considerable. In most countries, clarithromycin and metronidazole resistance rates are markedly high. H. pylori eradication improves the symptoms of functional dyspepsia, but only in a minority of patients. The frequency of idiopathic peptic ulcers seems to be rising and their prognosis is worse. Most patients with gastric cancer have, or have had, prior H. pylori infection. The risk of developing preneoplastic lesions depends on the type (strain) of the microorganism. To prevent the development of gastric cancer, eradication therapy should be administered early (before the development of intestinal metaplasia). Among H. pylori-infected patients, those who receive long-term treatment with proton pump inhibitors more frequently develop preneoplastic lesions. In patients who undergo endoscopic resection of early gastric cancer, H. pylori eradication reduces the incidence of metachronous tumors. Eradication therapy induces regression of MALT lymphoma in most patients and tumoral recurrence in the long term is exceptional; eradication is a reasonable option even when H. pylori infection has not been identified in patients with MALT lymphoma. Several diagnostic innovations were presented, such as some polymerase chain reaction techniques for use in gastric biopsy specimens or gastric juice. The efficacy of triple standard therapy is clearly inadequate. The superiority of "sequential" therapy over standard triple therapy has not been definitively established. "Concomitant" therapy is more effective and is simpler than "sequential" therapy. After failure of standard triple therapy, second
Markesich, D C; Anand, B S; Lew, G M; Graham, D Y
The mechanism by which Helicobacter pylori undermines host defence mechanisms is unclear. Several in vitro studies using soluble mucins have suggested that H pylori may compromise mucus function. Gastric mucus gel was obtained from 13 H pylori infected patients; six untreated subjects and seven after eradication of the infection. Gastric mucus is a non-Newtonian substance in that its viscosity changes with changing rates of shear, requiring mucus viscosity to be measured in a rotational cone-plate microviscometer. Viscosity was measured at shear rates varying from 1.15 s-1 to 46 s-1. The gastric mucus viscosity was significantly higher in patients infected with H pylori compared with mucus gel obtained after eradication of the infection. The results of our study suggest that the previous studies using in vitro methods involving soluble mucins or its components may have lead to erroneous conclusions about the in vivo interactions of H pylori and gastric mucus gel. The present findings argue against the hypothesis that degradation of gastric mucus by H pylori is important in the pathogenesis of peptic ulcer. PMID:7698685
Falsafi, Tahereh; Moradi, Parisa; Mahboubi, Mohaddese; Rahimi, Ebrahim; Momtaz, Hassan; Hamedi, Behzhad
Resistance of H. pylori strains to common antibiotics has been developed in different parts of the world and continues to increase. It is important to investigate the novel and efficient anti-H. pylori drugs, among which the plants would be suitable sources. Satureja bachtiarica Bunge is traditionally used as antimicrobial agent. In this study, we evaluated the antibacterial activity of S. bachtiarica Bunge essential oil against 10 clinical isolates of Helicobacter pylori by disc diffusion and agar dilution methods. The chemical composition of essential oil was analyzed by GC and GC-MS. Carvacrol (45.5%) and thymol (27.9%) were the primary constituents of oil, followed by p-cymene (4.4%), and γ-terpinene (4.0%). S. bachtiarica essential oil showed strong antibacterial activity against clinical isolates of H. pylori (17.6 ± 1.1 mm and 0.035 ± 0.13 μl/ml). Carvacrol, as the first main component, had a significant role in this effect, whereas in the presence of thymol, the antibacterial effect of carvacrol was reduced. Therefore, S. bachtiarica essential oil can be applied as an alternative agent for treatment of H. pylori infections. More studies would be required to better clarify its mechanism of action on H. pylori.
Suarez, Giovanni; Romero-Gallo, Judith; Piazuelo, M Blanca; Wang, Ge; Maier, Robert J; Forsberg, Lennart S; Azadi, Parastoo; Gomez, Martin A; Correa, Pelayo; Peek, Richard M
Helicobacter pylori (H. pylori) is the strongest known risk factor for gastric carcinogenesis. One cancer-linked locus is the cag pathogenicity island, which translocates components of peptidoglycan into host cells. NOD1 is an intracellular immune receptor that senses peptidoglycan from Gram-negative bacteria and responds by inducing autophagy and activating NF-κB, leading to inflammation-mediated bacterial clearance; however chronic pathogens can evade NOD1-mediated clearance by altering peptidoglycan structure. We previously demonstrated that the H. pylori cag(+) strain 7.13 rapidly induces gastric cancer in Mongolian gerbils. Using 2D-DIGE and mass spectrometry, we identified a novel mutation within the gene encoding the peptidoglycan deacetylase PgdA; therefore, we sought to define the role of H. pylori PgdA in NOD1-dependent activation of NF-κB, inflammation, and cancer. Coculture of H. pylori strain 7.13 or its pgdA(-) isogenic mutant with AGS gastric epithelial cells or HEK293 epithelial cells expressing a NF-κB reporter revealed that pgdA inactivation significantly decreased NOD1-dependent NF-κB activation and autophagy. Infection of Mongolian gerbils with an H. pylori pgdA(-) mutant strain led to significantly decreased levels of inflammation and malignant lesions in the stomach; however, preactivation of NOD1 before bacterial challenge reciprocally suppressed inflammation and cancer in response to wild-type H. pylori. Expression of NOD1 differs in human gastric cancer specimens compared with noncancer samples harvested from the same patients. These results indicate that peptidoglycan deacetylation plays an important role in modulating host inflammatory responses to H. pylori, allowing the bacteria to persist and induce carcinogenic consequences in the gastric niche.
Seo, Ji-Hyun; Woo, Hyang-Ok; Youn, Hee-Shang; Rhee, Kwang-Ho
Pediatric infection with Helicobacter pylori may occur early in childhood and persist lifelong. Global pediatric clinical studies have reported a decreasing tendency in the overall rate of H. pylori eradication. In pediatric patients with H. pylori infection, pediatric patients with peptic ulcer, and the first-degree relatives of patients with a history of gastric cancer, it is commonly recommended that H. pylori strains be eradicated. Antibiotic drug resistance to H. pylori, which has been reported to vary widely between geographic regions, is mainly associated with treatment failure in these patients. It is therefore imperative that the antibiotic resistance rates of H. pylori in children and adolescents be meticulously monitored across countries and throughout geographic regions. This paper particularly focuses on the antibiotic drug resistance of H. pylori and the thearpy of pediatric H. pylori infection cases.
Pérez-Figueroa, Erandi; Torres, Javier; Sánchez-Zauco, Norma; Contreras-Ramos, Alejandra; Alvarez-Arellano, Lourdes; Maldonado-Bernal, Carmen
TLRs and NLRs participate in the immune system recognition of Helicobacter pylori. However, little is known about the mechanisms leading to inflammasome activation by H. pylori and if NLRs in neutrophils are involved in the process. We studied how NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome components are involved in IL-1β maturation in human neutrophils in response to the infection and if they are dependent on T4SS (type IV secretion system) and TLRs. Human neutrophils were cultured and infected with the 26695 or the VirD4- H. pylori strains; the IL-1β concentration was analyzed by ELISA, and we also evaluated the activation of TLRs 2 and 4. The infection of neutrophils with both strains of H. pylori induced production of IL-1β and expression of the NLRP3 inflammasome components such as apoptosis-associated speck-like protein with CARD domain and NLRP3 protein. The infection also increased the activity of caspase-1, which is required for the maturation of IL-1β. Our study shows, for the first time, that H. pylori infection induces the expression and activation of components of NLRP3 inflammasomes in human neutrophils and that the activation is independent of a functional T4SS and TLR2 and TLR4. © The Author(s) 2015.
Malnick, Stephen David Howard; Melzer, Ehud; Attali, Malka; Duek, Gabriel; Yahav, Jacob
Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium that is present in nearly half the world’s population. It is the major cause of peptic ulcer disease and a recognized cause of gastric carcinoma. In addition, it is linked to non-ulcer dyspepsia, vitamin B12 deficiency, iron-deficient anemia and immune thrombocytopenic purpura. These conditions are indications for testing and treatment according to current guidelines. An additional indication according to the guidelines is “anyone with a fear of gastric cancer” which results in nearly every infected person being eligible for eradication treatment. There may be beneficial effects of H. pylori in humans, including protection from gastroesophageal reflux disease and esophageal adenocarcinoma. In addition, universal treatment will be extremely expensive (more than $32 billion in the United States), may expose the patients to adverse effects such as anaphylaxis and Clostridium difficile infection, as well as contributing to antibiotic resistance. There may also be an as yet uncertain effect on the fecal microbiome. There is a need for robust clinical data to assist in decision-making regarding treatment of H. pylori infection. PMID:25083071
Malnick, Stephen David Howard; Melzer, Ehud; Attali, Malka; Duek, Gabriel; Yahav, Jacob
Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium that is present in nearly half the world's population. It is the major cause of peptic ulcer disease and a recognized cause of gastric carcinoma. In addition, it is linked to non-ulcer dyspepsia, vitamin B12 deficiency, iron-deficient anemia and immune thrombocytopenic purpura. These conditions are indications for testing and treatment according to current guidelines. An additional indication according to the guidelines is "anyone with a fear of gastric cancer" which results in nearly every infected person being eligible for eradication treatment. There may be beneficial effects of H. pylori in humans, including protection from gastroesophageal reflux disease and esophageal adenocarcinoma. In addition, universal treatment will be extremely expensive (more than $32 billion in the United States), may expose the patients to adverse effects such as anaphylaxis and Clostridium difficile infection, as well as contributing to antibiotic resistance. There may also be an as yet uncertain effect on the fecal microbiome. There is a need for robust clinical data to assist in decision-making regarding treatment of H. pylori infection.
Iwańczak, Barbara; Francavailla, Ruggiero
This review concerns important pediatric studies published from April 2013 to March 2014. New data on pathogenesis have demonstrated that Th1 type cytokine secretion at the gastric level is less intense in children compared with adults. They have also shown that the most significant risk factor for Helicobacter pylori infection is the parents' origin and frequency of childcare in settings with a high prevalence of infection. A new hypothesis on the positive relationship between childhood H. pylori infection and the risk of gastric cancer in adults has been suggested which calls for an implementation of preventive programs to reduce the burden of childhood H. pylori infection in endemic areas. Several studies have investigated the role of H. pylori infection in iron-deficiency anemia, and results support the role of the bacterium in this condition. Antibiotic resistance is an area of intense research with data confirming an increase in antibiotic resistance, and the effect of CYP2C19 genetic polymorphism on proton-pump inhibitor metabolism should be further investigated as cure rates are lower in extensive metabolizers. Studies confirmed that probiotic supplementation may have beneficial effects on eradication and therapy-related side effects, particularly diarrhea in children. © 2014 John Wiley & Sons Ltd.
Gisbert, Javier P
This article summarizes the main conclusions of the studies presented at Digestive Disease Week this year (2015) related to Helicobacter pylori infection. Despite the undeniable widespread reduction in the prevalence of H. pylori infection, developing countries continue to have substantial infection rates. The prevalence of clarithromycin, metronidazole and quinolone resistance is markedly higher in most countries and continues to rise. Although H. pylori eradication reduces the incidence of gastric adenocarcinoma, it does not completely prevent its development; the presence of precancerous lesions--intestinal atrophy and metaplasia--is associated with a higher risk of developing this neoplasm, despite H. pylori eradication. The use of molecular diagnostic methods (polymerase chain reaction) in faecal samples could allow non-invasive evaluation of the antibiotic susceptibility of H. pylori. The effectiveness of standard triple therapy is clearly insufficient and continues to decrease. The effectiveness of sequential therapy in recent studies is lower than initially described and consequently this treatment cannot be recommended in clinical practice. Concomitant therapy is more effective and simpler than sequential therapy. In penicillin-allergic patients, quadruple therapy with bismuth is the treatment of choice in our environment. After the failure of standard triple therapy, second-line therapy with levofloxacin is effective and, moreover, is simpler and better tolerated than quadruple therapy with bismuth. Quadruple therapy with a proton pump inhibitor, bismuth, levofloxacin and amoxicillin is an effective (≥ 90% eradication), simple and safe second-line therapy if triple or quadruple therapy without bismuth (sequential or concomitant) fails to eradicate the infection. The new-generation quinolones, such as moxifloxacin or sitafloxacin, could be useful in second- or third-line rescue eradication therapy. Even after the failure of 3 eradication treatments, a
Djennane-Hadibi, Fazia; Bachtarzi, Mohamed; Layaida, Karim; Ali Arous, Nassima; Nakmouche, Mhamed; Saadi, Berkane; Tazir, Mohamed; Ramdani-Bouguessa, Nadjia; Burucoa, Christophe
Knowledge of local antibiotic resistance is crucial to adaptation for the choice of the optimal first-line treatment for Helicobacter pylori infection. Clarithromycin is a key component of the standard triple therapy largely used worldwide and, more particularly, in Algeria. Clarithromycin resistance is the main risk factor for treatment failure. The aim of this study was to evaluate, for the first time in Algeria, the prevalence of the primary resistance of H. pylori to clarithromycin. We conducted a prospective study (2008-2014) that included 195 Algerian patients referred for gastroduodenal endoscopy to two University Hospitals, one General Hospital, and several private gastroenterologists in Algiers (Algeria). One gastric biopsy was collected for the molecular detection of H. pylori and the mutations in 23S rRNA genes that confer resistance to clarithromycin with a quadruplex real-time PCR using Scorpion primers. The Scorpion PCR detected H. pylori DNA in 91 biopsies (47%). A mutation conferring resistance to clarithromycin was detected in 32 of the 91 positive patients (35%) and in 29 of the 88 positive patients never previously treated for an H. pylori infection (33%). The prevalence of primary resistance of H. pylori to clarithromycin was 33% in the Algerian population being studied. The high level of primary clarithromycin resistance in the H. pylori strains infecting the Algerian population that we report leads us to recommend the abandonment of the standard clarithromycin-based triple therapy as a first-line treatment in Algeria.
Valenzuela, Manuel; Cáceres, Aníbal; Almarza, Oscar; Bravo, Denisse; Soto, Sarita; Cerda, Oscar; Toledo, Héctor
Helicobacter pylori is a motile microaerophilic bacterium that colonizes the human stomach. H. pylori infection triggers gastric diseases, such as gastritis, peptic ulcer and gastric cancer. Stomach represents a barrier for microorganism colonization, particularly because of its high hydrochloric acid concentration. The main mechanism developed by H. pylori to maintain intracellular pH homeostasis in this environment is the urease activity. However, urease negative strains can be also isolated from clinical samples, suggesting that H. pylori presents other components involved in acid resistance. Here, we present some evidence that the arginine decarboxylase gene (speA) in H. pylori could be involved in an acid adaptation mechanism similar to the one in Enterobacteriaceae, which is dependent on the presence of arginine. Indeed, speA mRNA and protein expression are acutely induced by acid stress. Moreover, we showed that H. pylori uses arginine in an acid response mechanism required for its growth in acid conditions. Altogether, these results provide novel information regarding the H. pylori physiology and acid response mechanism. © 2014 John Wiley & Sons Ltd.
Backert, Steffen; Schmidt, Thomas P; Harrer, Aileen; Wessler, Silja
Highly organized intercellular tight and adherens junctions are crucial structural components for establishing and maintenance of epithelial barrier functions, which control the microbiota and protect against intruding pathogens in humans. Alterations in these complexes represent key events in the development and progression of multiple infectious diseases as well as various cancers. The gastric pathogen Helicobacter pylori exerts an amazing set of strategies to manipulate these epithelial cell-to-cell junctions, which are implicated in changing cell polarity, migration and invasive growth as well as pro-inflammatory and proliferative responses. This chapter focuses on the H. pylori pathogenicity factors VacA, CagA, HtrA and urease, and how they can induce host cell signaling involved in altering cell-to-cell permeability. We propose a stepwise model for how H. pylori targets components of tight and adherens junctions in order to disrupt the gastric epithelial cell layer, giving fresh insights into the pathogenesis of this important bacterium.
Moyat, Mati; Velin, Dominique
Helicobacter pylori (H. pylori) infection is one of the most common infections in human beings worldwide. H. pylori express lipopolysaccharides and flagellin that do not activate efficiently Toll-like receptors and express dedicated effectors, such as γ-glutamyl transpeptidase, vacuolating cytotoxin (vacA), arginase, that actively induce tolerogenic signals. In this perspective, H. pylori can be considered as a commensal bacteria belonging to the stomach microbiota. However, when present in the stomach, H. pylori reduce the overall diversity of the gastric microbiota and promote gastric inflammation by inducing Nod1-dependent pro-inflammatory program and by activating neutrophils through the production of a neutrophil activating protein. The maintenance of a chronic inflammation in the gastric mucosa and the direct action of virulence factors (vacA and cytotoxin-associated gene A) confer pro-carcinogenic activities to H. pylori. Hence, H. pylori cannot be considered as symbiotic bacteria but rather as part of the pathobiont. The development of a H. pylori vaccine will bring health benefits for individuals infected with antibiotic resistant H. pylori strains and population of underdeveloped countries.
Zheng, Pei; Zhou, Weiying
Objective: The correlation between periodontitis and Helicobacter pylori (H. pylori) infection in the mouth was analyzed. Method: 70 elderly patients with periodontitis treated at our hospital from January 2013 to December 2014 were recruited. Dental plaques and gargle were collected for H. pylori detection using PCR technique. Periodontal health status of the patients was recorded. 70 control cases with healthy periodontium were also included. The symptoms of H. pylori infection in the mouth were compared between the two groups, and the results were analyzed statistically. Results: The positive rate of urease C gene of H. pylori in the periodontitis group was 71.4%; the positive rate of cagA gene was 35.7%. The positive rate of urease C gene of H. pylori in the control group was 34.3% and that of cagA gene was 12.9%. The two groups did not show significant differences in these two indicators (P<0.05). The positive detection rate of urease C gene of H. pylori in subgingival plaques was higher than that in supragingival plaques, and the difference was of statistical significance (P<0.05). The positive detection rate of H. pylori in patients with moderate and severe periodontitis was obviously higher than that of patients with mild periodontitis (P<0.05). Conclusion: Periodontal health status of elderly people with periodontitis correlated with H. pylori infection in the stomach. PMID:26629215
Al-Sinani, Siham; Sharef, Sharef W; Al-Naamani, Khalid; Al-Sharji, Hyatt
Helicobacter pylori (H. pylori) infection is the most common chronic bacterial infection in humans. Its prevalence in Omani adults and children is not known. To report histology-based H. pylori infection prevalence in Omani children. A retrospective study of biopsy proven H. pylori infection in children over a 3 year period in a single center. Age, gender, indication for endoscopy, history of recurrent abdominal pain, and anemia were compared between H. pylori-positive and negative children. Of 143 patients who underwent endoscopy, gastric biopsies were available on 112. The overall prevalence of biopsy proven H. pylori infection was 25%. The prevalence in children with recurrent abdominal pain was 30% compared to 22% in children who underwent endoscopy for other indications (p = .382). The prevalence increased from 7% in children aged <5 years, to 33% in those aged between 5 and 10 years (p = .010). There was no significant difference in the prevalence between the 5-10 years age group (33%) and older age group (29%) (p = .814). There was no significant difference in gender or anemia between the two groups. This study represents the first reported study on the prevalence of biopsy proven H. pylori infection in Omani children. H. pylori infection prevalence is 25%, is lower than regional and many Arab countries. The prevalence appears to increase till age of 5 years. There was no significant association between H. pylori and recurrent abdominal pain, gender, or anemia. © 2014 John Wiley & Sons Ltd.
Moyat, Mati; Velin, Dominique
Helicobacter pylori (H. pylori) infection is one of the most common infections in human beings worldwide. H. pylori express lipopolysaccharides and flagellin that do not activate efficiently Toll-like receptors and express dedicated effectors, such as γ-glutamyl transpeptidase, vacuolating cytotoxin (vacA), arginase, that actively induce tolerogenic signals. In this perspective, H. pylori can be considered as a commensal bacteria belonging to the stomach microbiota. However, when present in the stomach, H. pylori reduce the overall diversity of the gastric microbiota and promote gastric inflammation by inducing Nod1-dependent pro-inflammatory program and by activating neutrophils through the production of a neutrophil activating protein. The maintenance of a chronic inflammation in the gastric mucosa and the direct action of virulence factors (vacA and cytotoxin-associated gene A) confer pro-carcinogenic activities to H. pylori. Hence, H. pylori cannot be considered as symbiotic bacteria but rather as part of the pathobiont. The development of a H. pylori vaccine will bring health benefits for individuals infected with antibiotic resistant H. pylori strains and population of underdeveloped countries. PMID:24914318
Liechti, George; Goldberg, Joanna B.
The bacterial pathogen Helicobacter pylori is capable of colonizing the gastric mucosa of the human stomach using a variety of factors associated with or secreted from its outer membrane (OM). Lipopolysaccharide (LPS) and numerous OM proteins have been shown to be involved in adhesion and immune stimulation/evasion. Many of these factors are essential for colonization and/or pathogenesis in a variety of animal models. Despite this wide array of potential targets present on the bacterial surface, the ability of H. pylori to vary its OM profile limits the effectiveness of vaccines or therapeutics that target any single one of these components. However, it has become evident that the proteins comprising the complexes that transport the majority of these molecules to the OM are highly conserved and often essential. The field of membrane biogenesis has progressed remarkably in the last few years, and the possibility now exists for targeting the mechanisms by which β-barrel proteins, lipoproteins, and LPS are transported to the OM, resulting in loss of bacterial fitness and significant altering of membrane permeability. In this review, the OM transport machinery for LPS, lipoproteins, and outer membrane proteins (OMPs) are discussed. While the principal investigations of these transport mechanisms have been conducted in Escherichia coli and Neisseria meningitidis, here these systems will be presented in the genetic context of ε proteobacteria. Bioinformatic analysis reveals that minimalist genomes, such as that of Helicobacter pylori, offer insight into the smallest number of components required for these essential pathways to function. Interestingly, in the majority of ε proteobacteria, while the inner and OM associated apparatus of LPS, lipoprotein, and OMP transport pathways appear to all be intact, most of the components associated with the periplasmic compartment are either missing or are almost unrecognizable when compared to their E. coli counterparts. Eventual
Ghaith, Doaa; Elzahry, Mohammad; Mostafa, Gehan; Mostafa, Sally; Elsherif, Rasha; Ramzy, Iman
Clarithromycin is a main component of the recommended first-line triple therapy for Helicobacter pylori in Egypt. We aimed in our study to investigate the prevalence of clarithromycin-resistant H. pylori strains due to the point mutations at domain V of the H. pylori 23S rRNA among the Egyptian population using the polymerase chain reaction/restricted fragment length polymorphism (PCR/RFLP) assay. Gastric biopsies obtained from 100 dyspeptic patients who consecutively attended at Cairo University Hospital during the period from January to November 2013 were subjected to PCR/RFLP in order to detect the point mutations at domain V of the H. pylori 23S rRNA associated with clarithromycin resistance. The PCR amplicon of the 23S H. pylori rRNA is restricted with MboII for detection of A2142G mutation and with BsaI for A2143G mutation. The prevalence of H. pylori infection among 100 patients was 70%; clarithromycin resistance was detected in 39/70 (57.7%) of positive H. pylori isolates. Occurrence of 23S rRNA A2142G mutations resulted in two DNA fragments (418 and 350 bp) by PCR-RFLP; on the other hand, no A2143G mutations were detected. The high prevalence of clarithromycin resistance (57.7%) caused by A2142G mutations at domain V of the H. pylori 23S rRNA may mandate changing of the standard clarithromycin-containing triple therapy. The PCR/RFLP assay was a rapid and accurate method for molecular detection of H. pylori infection in addition to determination of different nucleotide mutations causing clarithromycin resistance.
Wang, X M; Yee, K C; Hazeki-Taylor, N; Li, J; Fu, H Y; Huang, M L; Zhang, G Y
The present study was designed to explore the existence of oral Helicobacter pylori (H. pylori), its relationship in the oral cavity to the success rate of eradication of the gastric H. pylori infection, and to determine if the mouthwash solution contained lysine (0.4%) and glycerol monolaurate (0.2%) (LGM) could eliminate oral H. pylori, as well as using the saliva H. pylori culture to confirm the existence of oral H. pylori. A total of 159 symptomatic individuals with stomach pain and 118 asymptomatic individuals with no stomach complaints, were recruited and tested using the saliva H. pylori antigen test (HPS), the H. pylori flagellin test (HPF), the urea breath test (UBT C(13)) and the polymerase chain reaction (PCR) test, which tests were also confirmed by saliva culture. The test subjects also received various treatments. It was found that the H. pylori antigen exists in the oral cavity in UBT C(13) negative individuals. Traditional treatment for gastric eradication had only a 10.67 percent (10.67%) effectiveness rate on the oral H. pylori infection. In groups of patients with the oral H. pylori infection, but with negative UBT C(13), a mouthwash solution provided a 72.58% effectiveness rate in the 95% of the confidence interval (CI) ranges on the oral H. pylori infection. Traditional drug gastric eradication and teeth cleaning (TC) had less than a 10% effectiveness rate. Treatment of the oral infection increased the success rate of eradication of the stomach infection from 61.33% to 82.26% in the 95% CI ranges. We concluded that the successful rate of eradication of gastric H. pylori bears a significant relationship to the oral infection from H. pylori.
Suarez, Giovanni; Romero-Gallo, Judith; Piazuelo, M. Blanca; ...
Helicobacter pylori is the strongest known risk factor for gastric carcinogenesis. One cancer-linked locus is the cag pathogenicity island, which translocates components of peptidoglycan (PGN) into host cells. NOD1 is an intracellular immune receptor that senses PGN from Gram-negative bacteria and responds by inducing autophagy and activating NF-κB, leading to inflammation-mediated bacterial clearance; however chronic pathogens can evade NOD1-mediated clearance by altering PGN structure. We previously demonstrated that the H. pylori cag+ strain 7.13 rapidly induces gastric cancer in Mongolian gerbils. Using 2D-DIGE and mass spectrometry, we identified a novel mutation within the gene encoding the peptidoglycan deacetylase PgdA; therefore,more » we sought to define the role of H. pylori PgdA in NOD1-dependent activation of NF-κB, inflammation, and cancer. Co-culture of H. pylori strain 7.13 or its pgdA$-$ isogenic mutant with AGS gastric epithelial cells or HEK293 epithelial cells expressing a NF-κB reporter revealed that pgdA inactivation significantly decreased NOD1-dependent NF-κB activation and autophagy. Infection of Mongolian gerbils with an H. pylori pgdA$-$ mutant strain led to significantly decreased levels of inflammation and malignant lesions in the stomach; however, pre-activation of NOD1 prior to bacterial challenge reciprocally suppressed inflammation and cancer in response to wild-type H. pylori. Expression of NOD1 differs in human gastric cancer specimens compared to non-cancer samples harvested from the same patients. In conclusion, these results indicate that PGN deacetylation plays an important role in modulating host inflammatory responses to H. pylori, allowing the bacteria to persist and induce carcinogenic consequences in the gastric niche.« less
Turner, Lorinda; Praszkier, Judyta; Hutton, Melanie L; Steer, David; Ramm, Georg; Kaparakis-Liaskos, Maria; Ferrero, Richard L
Multiple studies have established the importance of the tol-pal gene cluster in bacterial cell membrane integrity and outer membrane vesicle (OMV) formation in Escherichia coli. In contrast, the functions of Tol-Pal proteins in pathogenic organisms, including those of the Epsilonproteobacteria, remain poorly if at all defined. The aim of this study was to characterize the roles of two key components of the Tol-Pal system, TolB and Pal, in OMV formation in the pathogenic bacterium, Helicobacter pylori. H. pylori ΔtolB, Δpal and ΔtolBpal mutants, as well as complemented strains, were generated and assessed for changes in morphology and OMV production by scanning electron microscopy and enzyme-linked immunoassay (ELISA), respectively. The protein content and pro-inflammatory properties of OMVs were determined by mass spectroscopy and interleukin-8 (IL-8) ELISA on culture supernatants from OMV-stimulated cells, respectively. H. pylori ΔtolB and Δpal bacteria exhibited aberrant cell morphology and/or flagella biosynthesis. Importantly, the disruption of H. pylori tolB but not pal resulted in a significant increase in OMV production. The OMVs from H. pylori ΔtolB and Δpal bacteria harbored many of the major outer membrane and virulence proteins observed in wild-type (WT) OMVs. Interestingly, ΔtolB, Δpal and ΔtolBpal OMVs induced significantly higher levels of IL-8 production by host cells, compared with WT OMVs. This work demonstrates that TolB and Pal are important for membrane integrity in H. pylori. Moreover, it shows how H. pylori tolB-pal genes may be manipulated to develop "hypervesiculating" strains for vaccine purposes. © 2015 John Wiley & Sons Ltd.
Rhee, Yun-Hee; Ku, Hyun-Jeong; Noh, Hye-Ji; Cho, Hyang-Hyun; Kim, Hee-Kyong; Ahn, Jin-Chul
AIM To investigate the bactericidal effects of calcium chelated N-acetylneuraminic acid-glycomacropeptide (CaG-NANA) against Helicobacter pylori (H. pylori). METHODS For manufacture of CaG-NANA, calcium (Ca) was combined with glycomacropeptide (GMP) by chelating, and N-acetylneuraminic acid (NANA) was produced with Ca-GMP substrate by an enzymatic method. The final concentration of each component was 5% Ca, 7% NANA, 85% GMP, and 3% water. For in vitro study, various concentrations of CaG-NANA were investigated under the minimal inhibitory concentration (MIC). For in vivo study, CaG-NANA was administered orally for 3 wk after H. pylori infection. The levels of inflammatory cytokines in blood were analyzed by enzyme-linked immunosorbent assay and eradication of H. pylori was assessed by histological observation. RESULTS The time-kill curves showed a persistent decrease in cell numbers, which depended on the dose of CaG-NANA, and MIC of CaG-NANA against H. pylori was 0.5% in vitro. Histopathologic observation revealed no obvious inflammation or pathologic changes in the gastric mucosa in the CaG-NANA treatment group in vivo. The colonization of H. pylori was reduced after CaG-NANA treatment. The levels of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, and IL-10 were also decreased by CaG-NANA. CONCLUSION CaG-NANA demonstrates effective anti-bactericidal activity against H. pylori both in vitro and in vivo. PMID:27895975
Zanotti, Giuseppe; Cendron, Laura
Proteins secreted by Helicobacter pylori (H. pylori), an important human pathogen responsible for severe gastric diseases, are reviewed from the point of view of their biochemical characterization, both functional and structural. Despite the vast amount of experimental data available on the proteins secreted by this bacterium, the precise size of the secretome remains unknown. In this review, we consider as secreted both proteins that contain a secretion signal for the periplasm and proteins that have been detected in the external medium in in vitro experiments. In this way, H. pylori’s secretome appears to be composed of slightly more than 160 proteins, but this number must be considered very cautiously, not only because the definition of secretome itself is ambiguous but also because the included proteins were observed as secreted in in vitro experiments that were not representative of the environmental situation in vivo. The proteins that appear to be secreted can be grouped into different classes: enzymes (48 proteins), outer membrane proteins (43), components of flagella (11), members of the cytotoxic-associated genes pathogenicity island or other toxins (8 and 5, respectively), binding and transport proteins (9), and others (11). A final group, which includes 28 members, is represented by hypothetical uncharacterized proteins. Despite the large amount of data accumulated on the H. pylori secretome, a considerable amount of work remains to reach a full comprehension of the system at the molecular level. PMID:24587618
Yee, John K C
Over the past several years, the severity of Helicobacter pylori (H. pylori) infections has not significantly diminished. After successful eradication, the annual H. pylori recurrence rate is approximately 13% due to oral H. pylori infection. Established clinical diagnostic techniques do not identify an oral etiologic basis of H. pylori prior to gastric infection. There has been disagreement as to whether oral infection of H. pylori exists or not, with no definite conclusion. In medical practice, negative results with the urea breath test suggest that the stomach infection of H. pylori is cured in these patients. In fact, patients can present negative urea breath test results and yet exhibit H. pylori infection due to oral infection. The present paper provides evidence that H. pylori oral infection is nonetheless present, and the oral cavity represents a secondary site for H. pylori colonization.
Yee, John KC
Over the past several years, the severity of Helicobacter pylori (H. pylori) infections has not significantly diminished. After successful eradication, the annual H. pylori recurrence rate is approximately 13% due to oral H. pylori infection. Established clinical diagnostic techniques do not identify an oral etiologic basis of H. pylori prior to gastric infection. There has been disagreement as to whether oral infection of H. pylori exists or not, with no definite conclusion. In medical practice, negative results with the urea breath test suggest that the stomach infection of H. pylori is cured in these patients. In fact, patients can present negative urea breath test results and yet exhibit H. pylori infection due to oral infection. The present paper provides evidence that H. pylori oral infection is nonetheless present, and the oral cavity represents a secondary site for H. pylori colonization. PMID:26811613
Dzierzanowska-Fangrat, Katarzyna; Lehours, Philippe; Mégraud, Francis; Dzierzanowska, Danuta
A growing interest in non-invasive tests for the detection of Helicobacter pylori has been observed recently, reflecting a large number of studies published this year. New tests have been validated, and the old ones have been used in different clinical situations or for different purposes. Stool antigen tests have been extensively evaluated in pre- and post-treatment settings both in adults and children, and the urea breath test has been studied as a predictor of bacterial load, severity of gastric inflammation, and response to eradication treatment. Several studies have also explored the usefulness of some serologic markers as indicators of the gastric mucosa status. With regard to invasive tests, molecular methods are being used more and more, but the breakthrough this year was the direct in vivo observation of H. pylori during endoscopy.
Dudley, Jonathan; Wieczorek, Tad; Selig, Martin; Cheung, Hoiwan; Shen, Jeanne; Odze, Robert; Deshpande, Vikram; Zukerberg, Lawrence
Helicobacter pylori organisms have been observed deep within the stomach mucosa with an "intracellular" appearance, although the clinicopathological characteristics of such cases remain poorly understood. We analyzed 18 cases of deep mucosal H pylori and associated clinical (sex, age, history of H pylori infection, or proton pump inhibitor [PPI] use, medications, smoking, alcohol use, comorbidities, treatment response) and pathological (presence of lymphoid aggregates, intestinal metaplasia, PPI effect, active and/or chronic inflammation, quantity of invasive versus surface H pylori) characteristics. Electron microscopy was performed on 6 cases with the highest burden of invasive H pylori. Within our sample, 3 of 16 had a history of H pylori infection, 10 of 15 were receiving PPIs at the time of biopsy, and 12 of 13 had a negative posttreatment follow-up. Histology revealed that invasive H pylori were more commonly associated with chronic inflammation, in both the antrum (15/15 chronic, 8/15 acute) and fundus (17/18 chronic, 8/18 acute). Electron microscopy showed organisms within intercellular and luminal spaces, but no intracellular organisms. Deep mucosal H pylori often have an intracellular appearance but are contained within intercellular and luminal spaces and are responsive to standard therapy. Copyright © 2016 Elsevier Inc. All rights reserved.
Homan, Matjaž; Orel, Rok
Helicobacter pylori (H. pylori) is considered an etiologic factor for the development of peptic ulcer disease, gastric adenocarcinoma, and MALT lymphoma. Therapeutic schemes to eradicate the bacteria are based on double antibiotic therapy and proton pump inhibitor. Despite many therapeutic improvements in H. pylori eradication treatment, it is still associated with high infection rate also in developed countries. Bacterial resistance and adverse events occurrence are among most frequent causes for anti- H. pylori treatment failure. Several studies have reported that certain probiotic strains can exhibit inhibitory activity against H. pylori bacteria. In addition, some probiotic strains can reduce the occurrence of side effects due to antibiotic therapy and consequently increase the H. pylori eradication rate. The results of the prospective double-blind placebo-controlled studies suggest that specific probiotics, such as S. boulardii and L. johnsonni La1 probably can diminish the bacterial load, but not completely eradicate the H. pylori bacteria. Furthermore, it seems that supplementation with S. boulardii is a useful concomitant therapy in the standard H. pylori eradication treatment protocol and most probably increases eradication rate. L. reuteri is equally effective, but more positive studies are needed. Finally, probiotic strains, such as S. boulardii, L. reuteri and L. GG, decrease gastrointestinal antibiotic associated adverse effects.
Homan, Matjaž; Orel, Rok
Helicobacter pylori (H. pylori) is considered an etiologic factor for the development of peptic ulcer disease, gastric adenocarcinoma, and MALT lymphoma. Therapeutic schemes to eradicate the bacteria are based on double antibiotic therapy and proton pump inhibitor. Despite many therapeutic improvements in H. pylori eradication treatment, it is still associated with high infection rate also in developed countries. Bacterial resistance and adverse events occurrence are among most frequent causes for anti- H. pylori treatment failure. Several studies have reported that certain probiotic strains can exhibit inhibitory activity against H. pylori bacteria. In addition, some probiotic strains can reduce the occurrence of side effects due to antibiotic therapy and consequently increase the H. pylori eradication rate. The results of the prospective double-blind placebo-controlled studies suggest that specific probiotics, such as S. boulardii and L. johnsonni La1 probably can diminish the bacterial load, but not completely eradicate the H. pylori bacteria. Furthermore, it seems that supplementation with S. boulardii is a useful concomitant therapy in the standard H. pylori eradication treatment protocol and most probably increases eradication rate. L. reuteri is equally effective, but more positive studies are needed. Finally, probiotic strains, such as S. boulardii, L. reuteri and L. GG, decrease gastrointestinal antibiotic associated adverse effects. PMID:26457024
Lu, Bin; Li, Meng
Helicobacter pylori (H. pylori) infection is a major risk factor for gastric cancer (GC) development, which is one of the most challenging malignant diseases worldwide with limited treatments. In the multistep pathogenesis of GC, H. pylori infection slowly induces chronic active gastritis, which progresses through the premalignant stages of atrophic gastritis, intestinal metaplasia, and dysplasia, and then finally to GC. Although eradication of H. pylori is a reasonable approach for the prevention of GC, there have been some contradictory reports, with only some long-term follow-up data showing efficacy of this approach. The inconsistencies are likely due to the insufficient number of participants, relatively short follow-up periods, poor quality of study designs, and the degree and extent of preneoplastic changes at the time of H. pylori eradication. This review analyzes recent high-quality studies to resolve the discrepancies regarding the eradication of H. pylori for GC prevention. The relationship between H. pylori eradication and GC/precancerous lesions/metachronous GC is examined, and the cost-effectiveness of this strategy in the prevention of GC is assessed. Although it is assumed that eradication of H. pylori has the potential to prevent GC, the feasibility and appropriate timing of this strategy for cancer prevention remain to be determined. As a result, additional well-designed trials with longer follow-up periods are needed to clarify this issue.
Lu, Bin; Li, Meng
Helicobacter pylori (H. pylori) infection is a major risk factor for gastric cancer (GC) development, which is one of the most challenging malignant diseases worldwide with limited treatments. In the multistep pathogenesis of GC, H. pylori infection slowly induces chronic active gastritis, which progresses through the premalignant stages of atrophic gastritis, intestinal metaplasia, and dysplasia, and then finally to GC. Although eradication of H. pylori is a reasonable approach for the prevention of GC, there have been some contradictory reports, with only some long-term follow-up data showing efficacy of this approach. The inconsistencies are likely due to the insufficient number of participants, relatively short follow-up periods, poor quality of study designs, and the degree and extent of preneoplastic changes at the time of H. pylori eradication. This review analyzes recent high-quality studies to resolve the discrepancies regarding the eradication of H. pylori for GC prevention. The relationship between H. pylori eradication and GC/precancerous lesions/metachronous GC is examined, and the cost-effectiveness of this strategy in the prevention of GC is assessed. Although it is assumed that eradication of H. pylori has the potential to prevent GC, the feasibility and appropriate timing of this strategy for cancer prevention remain to be determined. As a result, additional well-designed trials with longer follow-up periods are needed to clarify this issue. PMID:24914325
Furuta, Takahisa; Delchier, Jean-Charles
It is well known that Helicobacter pylori infection is associated with many nonmalignant disorders such as gastritis, peptic ulcer, gastroesophageal reflux disease (GERD), gastric polyp, nonsteroidal anti-inflammatory drug (NSAID)/aspirin-induced gastric injury, and functional dyspepsia. In 2008, interesting articles on the association of H. pylori infection with these disorders were presented, some of which intended to reveal the mechanisms of inter-individual differences in response to H. pylori infection, and have demonstrated that genetic differences in host and bacterial factors as well as environmental factors account for these differences. A decline in the occurrence of peptic ulcer related to H. pylori was confirmed. An inverse relationship between H. pylori infection and GERD was also confirmed but the impact of gastric atrophy on the prevention of GERD remained debatable. For NSAID-induced gastric injury, eradication of H. pylori infection has been recommended. During this year, eradication of H. pylori infection was recommended for patients treated with antiplatelet therapy as well as aspirin and NSAID. It was also reported that for patients with functional dyspepsia, eradication of H. pylori offers a modest but significant benefit.
Chao, Chih-Yu; Wang, Chih-Hung; Che, Yu-Jui; Kao, Cheng-Yen; Wu, Jiunn-Jong; Lee, Gwo-Bin
Helicobacter pylori (H. pylori) is a species of bacteria that can colonize the human stomach mucosa. It is closely associated with gastric diseases such as ulcer and inflammation. Recently, some H. pylori strains were found to express resistance to a family of antibiotics known as quinolones due to single-point mutations. Although traditional polymerase chain reaction (PCR) and molecular diagnostic-based approaches can be used to determine the presence and abundance of antibiotic-resistant H. pylori strains, such processes are relatively expensive, labor-intensive, and require bulky and costly equipment. This study therefore reports an advanced diagnostic assay performed on an integrated microfluidic system for rapid detection of antibiotic resistance in H. pylori. The assay features three components: (1) nucleic acid extraction by specific probe-conjugated magnetic beads, (2) amplification of the target deoxyribonucleic acid (DNA) fragments by using single-nucleotide-polymorphism polymerase chain reaction (SNP-PCR), and (3) optical detection of the PCR products. The device integrates several microfluidic components including micro-pumps, normally-closed micro-valves, and reaction chambers such that the entire diagnostic assay can be automatically executed on a single microfluidic system within one hour with detection limits of 10(0), 10(2), and 10(2) bacterial cells for H. pylori detection and two different SNP sites strains. Three PCR-based assays for determining presence of H. pylori infection and two DNA single-point mutation assays aimed at determining whether the infected strains were resistant to quinolone can be performed simultaneously on a single chip, suggesting that this microfluidic system could be a promising tool for rapid diagnosis of the presence of antibiotic-resistant H. pylori strains. Copyright © 2015 Elsevier B.V. All rights reserved.
Herbarth, Olf; Bauer, Mario; Fritz, Gisela J; Herbarth, Petra; Rolle‐Kampczyk, Ulrike; Krumbiegel, Peter; Richter, Matthias; Richter, Thomas
The hygiene hypothesis postulates that the increase in atopic diseases may in part be due to diminished exposure to microorganisms. But it is unknown which type of infection does render protection. An epidemiological study was conducted in Leipzig, Germany, and its rural county, involving 3347 school starters. Two types of infection were considered: (1) gastrointestinal colonisation (Helicobacter pylori detection using in vivo [13C] urea breath test) and (2) respiratory infections (physician‐diagnosed lower (bronchitis) and upper (common cold) respiratory infections). H pylori colonisation was selected because it is very common and plays an important role in gastrointestinal disorders. Atopic eczema was selected as the (allergic) target variable because of its high frequency in the age of the study participants. The results, adjusted for relevant confounders, showed a significant inverse association between H pylori infection and eczema (adjusted odds ratio (aOR) = 0.31, p = 0.006) in children not predisposed to atopy. In contrast, bronchitis increased the risk of eczema (aOR = 1.98, p<0.001). Bacterial digestive tract colonisation (infection) seems to protect against eczema in comparison with the effect of respiratory tract infections. The hygiene hypothesis may be better explained when gastrointestinal and respiratory infections are subtly differentiated. PMID:17568058
Kusters, Johannes G.; van Vliet, Arnoud H. M.; Kuipers, Ernst J.
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. Unless treated, colonization usually persists lifelong. 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. PMID:16847081
Lee, W K; An, Y S; Kim, K H; Kim, S H; Song, J Y; Ryu, B D; Choi, Y J; Yoon, Y H; Baik, S C; Rhee, K H; Cho, M J
In this study, a Helicobacter pylori-Escherichia coli shuttle vector was constructed for transferring DNA into H. pylori. The smallest cryptic plasmid (1.2 kb), pHP489, among those harbored by 77 H. pylori isolates was selected as a base replicon for constructing vectors. HindIII-digested pHP489 was ligated with a kanamycin resistance gene [aph(3')-III], which originated from Campylobacter jejuni, to produce the recombinant plasmid pHP489K. pHP489K was efficiently transformed into and stably maintained in H. pylori strains. The shuttle vector pBHP489K (3.6 kb) was constructed by the recombination of pHP489, ColE1, and aph(3')-III sequences. pBHP489K was reciprocally transformed into and maintained in both H. pylori and E. coli. Introduction of the shuttle vector clone DNA (pBHP489K/AB; 6.7 kb), containing the ureA and ureB genes of H. pylori, into urease-negative mutants of H. pylori led to the restoration of their urease activity. The transformants were confirmed to contain the incoming plasmid DNA. pBHP489K satisfied the requirements for an H. pylori-E. coli shuttle vector, implying that it might be a useful vector for investigating pathogenicity and restriction-modification systems of H. pylori. PMID:9406406
Cremades, Nunilo; Velázquez-Campoy, Adrián; Martínez-Júlvez, Marta; Neira, José L; Pérez-Dorado, Inmaculada; Hermoso, Juan; Jiménez, Pilar; Lanas, Angel; Hoffman, Paul S; Sancho, Javier
Helicobacter pylori establishes life-long infections in the gastric mucosa of over 1 billion people worldwide. In many cases, without specific antimicrobial intervention, H. pylori infected individuals will develop type B gastritis, chronic peptic ulcers and, more rarely, gastric neoplasias. Conventional antimicrobial therapy has been complicated by dramatic increases in resistance to macrolides, metronidazole and fluoroquinolones. Here, we report the development of novel therapeutics that specifically target the unique flavodoxin component of an essential metabolic pathway of H. pylori. With the use of high-throughput screening methodology, we have tested 10,000 chemicals and have identified 29 compounds that bind flavodoxin, four of which interrupted in vitro electron transfer to flavodoxin physiological partners. Three of these compounds are bactericidal and promisingly selective for H. pylori. The minimal inhibitory concentrations of two of them are 10 times lower than their minimal cytotoxic concentrations for HeLa cells. Importantly, neither of the four inhibitors is toxic for mice after administration of 1-10 mg kg(-1) doses twice a day for 5 days. Enzymatic, thermodynamic and structural characterization of the inhibitor-flavodoxin complexes suggests these compounds could act by modifying the redox potentials of flavodoxin. These newly discovered inhibitors represent promising selective leads against the different diseases associated to H. pylori infection.
Mirzaei, Nasrin; Poursina, Farkhondeh; Moghim, Sharareh; Rahimi, Ebrahim; Safaei, Hajieh Ghasemian
Antibiotic resistance is an increasing problem throughout the developed world, and knowledge about different resistance mechanisms is consequential for efficient treatment of bacterial infections. Although metronidazole has been frequently used in treatment regimens for H. pylori infection, but antibiotic resistance is now a major contributing factor in treatment failure. Nevertheless metronidazole has been greatly used as a critical component of combination therapies for H. pylori infection. This study is trying to describe the mutational mechanisms of metronidazole resistance in H. pylori in our clinical isolates in Isfahanian patients, Iran and compare with the findings of previous studies in world. MIC values of metronidazole for H. pylori strains were determined by E- test. Both rdxA and glmM genes used for confirmation of isolates as H. pylori and then amplification of another rdxA oligonucleotide pair was done. Finally, the six resistant strains were sent to sequencing for other processing and further analysis was done by software. The result of six clinical isolates in comparison with 26695, J99 and 69A as a sensitive and resistant reference strains showed plenty of mutations. No frame shift and nonsense mutation was seen in our clinical isolates. An interesting finding in metronidazole-resistant strains in our study was the detection of one mutation not previously described in the literature in the rdxA gene and this W(209)R substitution presumably plays a role in inducing metronidazole resistance.
Mirzaei, Nasrin; Poursina, Farkhondeh; Moghim, Sharareh; Rahimi, Ebrahim; Safaei, Hajieh Ghasemian
Backgrounds: Antibiotic resistance is an increasing problem throughout the developed world, and knowledge about different resistance mechanisms is consequential for efficient treatment of bacterial infections. Although metronidazole has been frequently used in treatment regimens for H. pylori infection, but antibiotic resistance is now a major contributing factor in treatment failure. Nevertheless metronidazole has been greatly used as a critical component of combination therapies for H. pylori infection. Objective: This study is trying to describe the mutational mechanisms of metronidazole resistance in H. pylori in our clinical isolates in Isfahanian patients, Iran and compare with the findings of previous studies in world. Materials and Methods: MIC values of metronidazole for H. pylori strains were determined by E- test. Both rdxA and glmM genes used for confirmation of isolates as H. pylori and then amplification of another rdxA oligonucleotide pair was done. Finally, the six resistant strains were sent to sequencing for other processing and further analysis was done by software. Results: The result of six clinical isolates in comparison with 26695, J99 and 69A as a sensitive and resistant reference strains showed plenty of mutations. No frame shift and nonsense mutation was seen in our clinical isolates. Conclusion: An interesting finding in metronidazole-resistant strains in our study was the detection of one mutation not previously described in the literature in the rdxA gene and this W(209)R substitution presumably plays a role in inducing metronidazole resistance. PMID:24761398
Lin, Wen-Hsin; Wu, Chi-Rei; Fang, Tony J; Guo, Jiun-Ting; Huang, Shi-Ying; Lee, Meng-Shiou; Yang, Hsin-Ling
Ten strains of lactic acid bacteria (LAB) were investigated for their anti-Helicobacter pylori effects. The bactericidal activity and organic acid content in spent culture supernatants (SCS) from fermented milk were measured. In addition, the exclusion effect of SCS against H. pylori infection of human gastric epithelial AGS cells was assayed. Three LAB strains, LY1, LY5 and IF22, showed better anti-Helicobacter effects than the other strains. There were no significant differences in the bactericidal activity of LAB strains between original SCS, artificial SCS and SCS treated by heating or protease digestion. However, neutralised SCS lost this activity. These results suggest that the anti-H. pylori activity of SCS may be related to the concentration of organic acids and the pH value but not to protein components. In the AGS cell culture test, both fermented LY5-SCS and artificial LY5-SCS significantly reduced H. pylori infection and urease activity (P < 0.05). In this study, in vitro methods were used to screen potential probiotics with anti-H. pylori activity. This may provide an excellent and rapid system for studying probiotics in the functional food and dairy industries. Copyright © 2011 Society of Chemical Industry.
Gomes, Carolina-Cavaliéri; Gomez, Ricardo-Santiago; Zina, Lívia-Guimarães
Background Recurrent aphthous stomatitis (RAS) is a recurrent painful ulcerative disorder that commonly affects the oral mucosa. Local and systemic factors such as trauma, food sensitivity, nutritional deficiencies, systemic conditions, immunological disorders and genetic polymorphisms are associated with the development of the disease. Helicobacter pylori (H. pylori) is a gram-negative, microaerophile bacteria, that colonizes the gastric mucosa and it was previously suggested to be involved in RAS development. In the present paper we reviewed all previous studies that investigated the association between RAS and H. pylori. Material and Methods A search in Pubmed (MEDLINE) databases was made of articles published up until July 2015 using the following keywords: Helicobacter Pylori or H. pylori and RAS or Recurrent aphthous stomatitis. Results Fifteen experimental studies that addressed the relationship between infection with H. pylori and the presence of RAS and three reviews, including a systematic review and a meta-analysis were included in this review. The studies reviewed used different methods to assess this relationship, including PCR, nested PCR, culture, ELISA and urea breath test. A large variation in the number of patients included in each study, as well as inclusion criteria and laboratorial methods was observed. H. pylori can be detected in the oral mucosa or ulcerated lesion of some patients with RAS. The quality of the all studies included in this review was assessed using levels of evidence based on the University of Oxford’s Center for Evidence Based Medicine Criteria. Conclusions Although the eradication of the infection may affect the clinical course of the oral lesions by undetermined mechanisms, RAS ulcers are not associated with the presence of the bacteria in the oral cavity and there is no evidence that H. pylori infection drives RAS development. Key words:Campylobacter, elisa, h. pylori, Helicobacter Pylori, RAS, recurrent aphthous
Lam, Robert; Romanov, Vladimir; Johns, Kathy; Battaile, Kevin P.; Wu-Brown, Jean; Guthrie, Jennifer L.; Hausinger, Robert P.; Pai, Emil F.; Chirgadze, Nickolay Y.
Urease plays a central role in the pathogenesis of Helicobacter pylori in humans. Maturation of this nickel metalloenzyme in bacteria requires the participation of the accessory proteins UreD (termed UreH in H. pylori), UreF, and UreG which form sequential complexes with the urease apoprotein as well as UreE, a metallochaperone. Here, we describe the crystal structure of C-terminal truncated UreF from H. pylori (residues 1-233), the first UreF structure to be determined, at 1.55 Å resolution using SAD methods. UreF forms a dimer in vitro and adopts an all-helical fold congruent with secondary structure prediction. On the basis of evolutionary conservation analysis, the structure reveals a probable binding surface for interaction with other urease components as well as key conserved residues of potential functional relevance. PMID:20635345
Cardaropoli, Simona; Rolfo, Alessandro; Todros, Tullia
Helicobacter pylori (H. pylori) infection is investigated in gastric diseases even during pregnancy. In particular, this Gram-negative bacterium seems to be associated with hyperemesis gravidarum, a severe form of nausea and vomiting during pregnancy. During the last decade, the relationship among H. pylori and several extra-gastric diseases strongly emerged in literature. The correlation among H. pylori infection and pregnancy-related disorders was mainly focused on iron deficiency anemia, thrombocytopenia, fetal malformations, miscarriage, pre-eclampsia and fetal growth restriction. H. pylori infection may have a role in the pathogenesis of various pregnancy-related disorders through different mechanisms: depletion of micronutrients (iron and vitamin B12) in maternal anemia and fetal neural tube defects; local or systemic induction of pro-inflammatory cytokines release and oxidative stress in gastrointestinal disorders and pre-eclampsia; cross-reaction between specific anti-H. pylori antibodies and antigens localized in placental tissue and endothelial cells (pre-eclampsia, fetal growth restriction, miscarriage). Since H. pylori infection is most likely acquired before pregnancy, it is widely believed that hormonal and immunological changes occurring during pregnancy could activate latent H. pylori with a negative impact not only on maternal health (nutritional deficiency, organ injury, death), but also on the fetus (insufficient growth, malformation, death) and sometime consequences can be observed later in life. Another important issue addressed by investigators was to determine whether it is possible to transmit H. pylori infection from mother to child and whether maternal anti-H. pylori antibodies could prevent infant’s infection. Studies on novel diagnostic and therapeutic methods for H. pylori are no less important, since these are particularly sensitive topics in pregnancy conditions. It could be interesting to study the possible correlation between H
Frick-Cheng, Arwen E; Pyburn, Tasia M; Voss, Bradley J; McDonald, W Hayes; Ohi, Melanie D; Cover, Timothy L
Bacterial type IV secretion systems (T4SSs) can function to export or import DNA, and can deliver effector proteins into a wide range of target cells. Relatively little is known about the structural organization of T4SSs that secrete effector proteins. In this report, we describe the isolation and analysis of a membrane-spanning core complex from the Helicobacter pylori cag T4SS, which has an important role in the pathogenesis of gastric cancer. We show that this complex contains five H. pylori proteins, CagM, CagT, Cag3, CagX, and CagY, each of which is required for cag T4SS activity. CagX and CagY are orthologous to the VirB9 and VirB10 components of T4SSs in other bacterial species, and the other three Cag proteins are unique to H. pylori. Negative stain single-particle electron microscopy revealed complexes 41 nm in diameter, characterized by a 19-nm-diameter central ring linked to an outer ring by spoke-like linkers. Incomplete complexes formed by Δcag3 or ΔcagT mutants retain the 19-nm-diameter ring but lack an organized outer ring. Immunogold labeling studies confirm that Cag3 is a peripheral component of the complex. The cag T4SS core complex has an overall diameter and structural organization that differ considerably from the corresponding features of conjugative T4SSs. These results highlight specialized features of the H. pylori cag T4SS that are optimized for function in the human gastric mucosal environment. Type IV secretion systems (T4SSs) are versatile macromolecular machines that are present in many bacterial species. In this study, we investigated a T4SS found in the bacterium Helicobacter pylori. H. pylori is an important cause of stomach cancer, and the H. pylori T4SS contributes to cancer pathogenesis by mediating entry of CagA (an effector protein regarded as a "bacterial oncoprotein") into gastric epithelial cells. We isolated and analyzed the membrane-spanning core complex of the H. pylori T4SS and showed that it contains unique proteins
Martínez-Carrillo, D N; Atrisco-Morales, J; Hernández-Pando, R; Reyes-Navarrete, S; Betancourt-Linares, R; Cruz-del Carmen, I; Illades Aguiar, B; Román-Román, A; Fernández-Tilapa, G
Helicobacter pylori (H. pylori) is the main risk factor for the development of chronic gastritis, gastric ulcer, and gastric cancer. In H. pylori-infected individuals, the clinical result is dependent on various factors, among which are bacterial components, the immune response, and environmental influence. To compare IFN-γ expression with the H. pylori vacA and cagA genotypes in patients with chronic gastritis and patients with gastric cancer. Ninety-five patients diagnosed with chronic gastritis and 20 with gastric cancer were included in the study. Three gastric biopsies were taken; one was used for the molecular detection and genotyping of H. pylori; another was fixed in absolute alcohol and histologic sections were made for determining IFN-γ expression through immunohistochemistry. No differences were found in the cells that expressed IFN-γ between the patients with chronic gastritis (median percentage of positive cells: 82.6% in patients without H. pylori and 82% in infected persons) and those with gastric cancer (70.5% in H. pylori-negative patients and 78.5% in infected persons). IFN-γ expression was 69% in chronic gastritis patients infected with H. pylori vacAs2m2/cagA⁻ it was 86.5% in patients infected with H. pylori vacAs1m2/cagA⁻, 86.5% in vacAs1m1/cagA⁻, and 82% in vacAs1m1/cagA⁺. Similar data were found in the patients with gastric cancer. IFN-γ expression varied depending on the H. pylori vacA and cagA genotype, but not in accordance with the presence of chronic gastritis or gastric cancer.
Kim, SeGun; Hong, InPyo; Woo, SoonOk; Jang, HyeRi; Pak, SokCheon; Han, SangMi
Helicobacter pylori (H. pylori) is linked to the development of the majority of peptic ulcers and some types of gastric cancers, and its antibiotic resistance is currently found worldwide. This study is aimed at evaluating the anti-H. pylori activity of Korean acacia honey and isolating the related active components using organic solvents. The crude acacia honey was extracted with n-hexane, dichloromethane, ethyl acetate (EtOAc), and n-butanol. The EtOAc extract was subjected to octadecyl-silica chromatography. The extracts and fractions were then examined for anti-H. pylori activity using the agar well diffusion method. The antimicrobial activity of abscisic acid against H. pylori was investigated by determining the minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), and by performing a time-kill assay. Abscisic acid related to the botanical origins of acacia honey from Korea has been analyzed using ultra-performance liquid chromatography. The MICs and MBCs of abscisic acid were 2.7 ± 1.3 and 6.9 ± 1.9 μg/mL, respectively. The bactericidal activity of abscisic acid (at 10.8 μg/mL corresponding to 4 × MIC) killed the organism within 36-72 h. These results suggest that abscisic acid isolated from Korean acacia honey has antibacterial activity against H. pylori. Abscisic acid isolated from Korean acacia honey can be therapeutic and may be further exploited as a potential lead candidate for the development of treatments for H. pylori-induced infections. The crude acacia honey was extracted with n-hexane, dichloromethane, EtOAc, and n-butanolThe EtOAc extract yielded eight fractions and four subfractions were subsequently obtained chromatographicallyAbscisic acid was isolated from one subfractionAll the solvent extracts and fractions showed antibacterial activity against H. pyloriAbscisic acid exhibited antibacterial activity against H. pylori. Abbreviations used: MeOH: Methanol; EtOAc: Ethyl acetate; TSB: Trypticase soy broth
Helicobacter pylori (H. pylori) is the most common infection in humans, with a marked disparity between developed and developing countries. Although H. pylori infections are asymptomatic in most infected individuals, they are intimately related to malignant gastric conditions such as gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to benign diseases such as gastritis and duodenal and gastric peptic ulcers. Since it was learned that bacteria could colonize the gastric mucosa, there have been reports in the medical literature of over 50 extragastric manifestations involving a variety medical areas of specialization. These areas include cardiology, dermatology, endocrinology, gynecology and obstetrics, hematology, pneumology, odontology, ophthalmology, otorhinolaryngology and pediatrics, and they encompass conditions with a range of clear evidence between the H. pylori infection and development of the disease. This literature review covers extragastric manifestations of H. pylori infection in the hematology field. It focuses on conditions that are included in international consensus and management guides for H. pylori infection, specifically iron deficiency, vitamin B12 (cobalamin) deficiency, immune thrombocytopenia, and MALT lymphoma. In addition, there is discussion of other conditions that are not included in international consensus and management guides on H. pylori, including auto-immune neutropenia, antiphospholipid syndrome, plasma cell dyscrasias, and other hematologic diseases. PMID:25278680
Salmela, K S; Roine, R P; Höök-Nikanne, J; Kosunen, T U; Salaspuro, M
By virtue of possessing alcohol dehydrogenase activity, cytosol prepared from Helicobacter pylori produces toxic acetaldehyde from ethanol in vitro. To approach the in vivo situation in the stomach, we have now investigation whether intact H. pylori--without addition of exogenous nicotinamide adenine dinucleotide--also forms acetaldehyde. Furthermore, to assess the energy metabolism of H. pylori, we determined whether the alcohol dehydrogenase-catalyzed reaction can run in the opposite direction with ethanol as the end-product and thereby yield energy for the organism. Intact H. pylori formed acetaldehyde already at low ethanol concentrations (at 0.5% ethanol, acetaldehyde, 64 +/- 21 and 75 +/- 9 mumol/l (mean +/- SEM) for strains NCTC 11637 and NCTC 11638, respectively). H. pylori produced ethanol in concentrations that can be significant for the energy metabolism of the organism. Acetaldehyde production by H. pylori may be an important factor in the pathogenesis of gastroduodenal diseases associated with the organism. The primary function of H. pylori alcohol dehydrogenase may, however, be alcoholic fermentation and consequent energy production under microaerobic conditions.
Helicobacter pylori (H. pylori) has become accepted as a human pathogen for the development of gastritis and gastroduodenal ulcer. To develop a simple rat model of chronic H. pylori infection, male Sprague-Dawley rats were pretreated with streptomycin suspended in tap water (5 mg/mL) for 3 d. The rats were inoculated by gavage at 1 mL/rat with H. pylori suspension (5 × 10(8)-5 × 10(10) CFU/mL) twice daily at an interval of 4 h for three consecutive days. Two weeks after inoculation, rats were sacrificed and the stomachs were removed. Antral biopsies were performed for urease test and the stomachs were taken for histopathology. Successful H. pylori inoculation was defined as a positive urease test and histopathology. We reported a 69.8%-83.0% success rate for H. pylori infection using the urease test, and hematoxylin and eosin staining confirmed the results. Histopathological analysis detected bacteria along the mucous lining of the surface epithelium and crypt lumen and demonstrated mild to moderate gastric inflammation in successfully inoculated rats. We developed a simple rat model of chronic H. pylori infection for research into gastric microcirculatory changes and therapy with plant products.
Miftahussurur, Muhammad; Yamaoka, Yoshio; Graham, David Y
Gastric cancer is an inflammation-associated malignancy aetiologically related to infection with the bacterium, Helicobacter pylori, which is considered a necessary but insufficient cause. Unless treated, H. pylori causes life-long acute and chronic gastric inflammation resulting in progressive gastric mucosal damage that may result in gastric cancer. The rate of progression from superficial gastritis, to an atrophic metaplastic mucosa, and ultimately to cancer relates to the virulence of the infecting H. pylori as well as host and environmental factors. H. pylori virulence is a reflection of its propensity to cause severe gastric inflammation. Both mucosal inflammation and H. pylori can cause host genomic instability, including dysregulation of DNA mismatch repair, stimulation of expression of activation-induced cytidine deaminase, abnormal DNA methylation and dysregulation of micro RNAs, which may result in an accumulation of mutations and loss of normal regulation of cell growth. The difference in cancer risk between the most and least virulent H. pylori strain is only approximately 2-fold. Overall, none of the putative virulence factors identified to date have proved to be disease-specific. The presence, severity, extent and duration of inflammation appear to be the most important factors and current evidence suggests that any host, environmental or bacterial factor that reliably enhances the inflammatory response to the H. pylori infection increases the risk of gastric cancer.
Haley, Kathryn P.; Gaddy, Jennifer A.
Helicobacter pylori is a Gram-negative spiral-shaped bacterium that colonizes over half of the world's population. Chronic H. pylori infection is associated with increased risk for numerous disease outcomes including gastritis, dysplasia, neoplasia, B-cell lymphoma of mucosal-associated lymphoid tissue (MALT lymphoma), and invasive adenocarcinoma. The complex interactions that occur between pathogen and host are dynamic and exquisitely regulated, and the relationship between H. pylori and its human host are no exception. To successfully colonize, and subsequently persist, within the human stomach H. pylori must temporally regulate numerous genes to ensure localization to the gastric lumen and coordinated expression of virulence factors to subvert the host's innate and adaptive immune response. H. pylori achieves this precise gene regulation by sensing subtle environmental changes including host-mediated alterations in nutrient availability and responding with dramatic global changes in gene expression. Recent studies revealed that the presence or absence of numerous metal ions encountered in the lumen of the stomach, or within host tissues, including nickel, iron, copper and zinc, can influence regulatory networks to alter gene expression in H. pylori. These expression changes modulate the deployment of bacterial virulence factors that can ultimately influence disease outcome. In this review we will discuss the environmental stimuli that are detected by H. pylori as well as the trans regulatory elements, specifically the transcription regulators and transcription factors, that allow for these significant transcriptional shifts. PMID:26388855
Musgrove, C; Bolton, F J; Krypczyk, A M; Temperley, J M; Cairns, S A; Owen, W G; Hutchinson, D N
The presence of Campylobacter pylori, histologically diagnosed gastritis, and antibodies to C pylori were determined in a series of 113 patients undergoing endoscopy. Paired biopsy specimens from the fundus, body, and antrum were collected from 59 patients and from the antrum of 54 patients. The presence of C pylori was confirmed by either culture or silver stain in 30 of 59, 31 of 59, and 54 of 103 biopsy specimens from the fundus, body, and antrum, respectively. Of the specimens which contained C pylori 20 of 30 (66%) from the fundus, 25 of 31 (80%) from the body, and 54 (100%) from the antrum showed gastritis. C pylori and gastritis were shown in seven of nine (78.1%) of patients with gastric ulcers and in nine of 11 (82%) of patients with duodenal ulcers. Using an enzyme linked immunosorbent assay (ELISA) technique to detect IgG antibody to C pylori, all patients with histologically diagnosed gastritis and organisms present had titres of greater than or equal to 640; eight of 39 (21%) of patients without gastritis and without organisms gave similar titres. Hence the presence of C pylori was associated with gastritis and with raised titres of IgG antibody. Images Fig 1 Fig 2 PMID:3225334
Misra, Vatsala; Pandey, Renu; Misra, Sri Prakash; Dwivedi, Manisha
Helicobacter pylori (H. pylori) is a gram negative microaerophilic bacterium which resides in the mucous linings of the stomach. It has been implicated in the causation of various gastric disorders including gastric cancer. The geographical distribution and etiology of gastric cancer differ widely in different geographical regions and H. pylori, despite being labeled as a grade I carcinogen, has not been found to be associated with gastric cancer in many areas. Studies in Asian countries such as Thailand, India, Bangladesh, Pakistan, Iran, Saudi Arabian countries, Israel and Malaysia, have reported a high frequency of H. pylori infection co-existing with a low incidence of gastric cancer. In India, a difference in the prevalence of H. pylori infection and gastric cancer has been noted even in different regions of the country leading to a puzzle when attempting to find the causes of these variations. This puzzle of H. pylori distribution and gastric cancer epidemiology is known as the Indian enigma. In this review we have attempted to explain the Indian enigma using evidence from various Indian studies and from around the globe. This review covers aspects of epidemiology, the various biological strains present in different parts of the country and within individuals, the status of different H. pylori-related diseases and the molecular pathogenesis of the bacterium.
Talebi Bezmin Abadi, Amin
Over three decades have passed since the discovery of Helicobacter pylori (H. pylori), and yet many questions about its treatment remain unanswered. For example, there is no certainty regarding continued use of current antibiotic therapy against H. pylori. The bad news is that even combined regimens are also unable to eradicate bacterial colonization. The worst problem with H. pylori chemotherapy is that even if we identify the most successful regimen, it cannot eliminate the risk of re-infection. This problem is further complicated by the fact that clinicians have no information as to whether probiotics are useful or not. Moreover, to date, we have no large scale produced vaccine effective against H. pylori. Due to the relatively rapid and abundant dissemination of guidelines globally reported concerning management of gastric cancer prevention and therapeutic regimens, clinicians may choose a vaccine as better effective weapon against H. pylori. Therefore, a radical shift in adopted strategies is needed to guide ultimate decisions regarding H. pylori management. In light of failures in vaccine projects, we should identify better vaccine design targeting conserved/essential genes. The unique character and persistence of H. pylori pose obstacles to making an effective vaccine. Preferably, in developing countries, the best reasonable and logical approach is to recommend prophylactic H. pylori vaccine among children as an obligatory national program to limit primary colonization. Trying to produce a therapeutic vaccine would be postponed until later. In reality, we should not forget to prescribe narrow spectrum antibiotics. In the current review, I draw a route to define the best adopted strategy against this rogue bacterium.
Diaconu, S; Predescu, A; Moldoveanu, A; Pop, C S; Fierbințeanu-Braticevici, C
Helicobacter pylori is a spiral-shaped bacterium that grows in the digestive tract and may be present in more than half of the world's population. The clinical features of Helicobacter pylori range from asymptomatic gastritis to gastrointestinal malignancy. Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade B-cell marginal zone lymphoma and Helicobacter pylori has been detected in more than 75% of the patients with MALT lymphoma. Many tests for the detection of Helicobacter pylori are available, including antibody tests, urea breath tests, stool antigen tests and endoscopic biopsies. The eradication of Helicobacter pylori usually prevents the return of ulcers and ulcer complications even after appropriate medications such as PPIs are stopped. The eradication of Helicobacter pylori is important in the treatment of the rare condition of the stomach known as MALT lymphoma. The treatment of Helicobacter pylori to prevent stomach cancer is controversial. Confirmation of eradication is recommended in associated ulcers, persistent dyspepsia despite a test-and-treat approach, MALT lymphoma, and previous treatment for early-stage gastric cancer. The urea breath test and stool antigen test can be used to confirm the eradication and should be performed at least 4 weeks after the completion of therapy. Several diseases have been reported to be associated with Helicobacter pylori infection, including hematologic diseases, such as ITP, idiopathic iron deficiency anemia and vitamin B12 deficiency. There is a positive trend in the association between Helicobacter pylori infection and neurodegenerative disorders and new data showed a reduced risk of death due to stroke and lung cancer but an increased risk of preeclampsia in infected women, which requires further investigations.
Talebi Bezmin Abadi, Amin
Over three decades have passed since the discovery of Helicobacter pylori (H. pylori), and yet many questions about its treatment remain unanswered. For example, there is no certainty regarding continued use of current antibiotic therapy against H. pylori. The bad news is that even combined regimens are also unable to eradicate bacterial colonization. The worst problem with H. pylori chemotherapy is that even if we identify the most successful regimen, it cannot eliminate the risk of re-infection. This problem is further complicated by the fact that clinicians have no information as to whether probiotics are useful or not. Moreover, to date, we have no large scale produced vaccine effective against H. pylori. Due to the relatively rapid and abundant dissemination of guidelines globally reported concerning management of gastric cancer prevention and therapeutic regimens, clinicians may choose a vaccine as better effective weapon against H. pylori. Therefore, a radical shift in adopted strategies is needed to guide ultimate decisions regarding H. pylori management. In light of failures in vaccine projects, we should identify better vaccine design targeting conserved/essential genes. The unique character and persistence of H. pylori pose obstacles to making an effective vaccine. Preferably, in developing countries, the best reasonable and logical approach is to recommend prophylactic H. pylori vaccine among children as an obligatory national program to limit primary colonization. Trying to produce a therapeutic vaccine would be postponed until later. In reality, we should not forget to prescribe narrow spectrum antibiotics. In the current review, I draw a route to define the best adopted strategy against this rogue bacterium. PMID:27003991
Diaconu, S; Predescu, A; Moldoveanu, A; Pop, CS; Fierbințeanu-Braticevici, C
Helicobacter pylori is a spiral-shaped bacterium that grows in the digestive tract and may be present in more than half of the world’s population. The clinical features of Helicobacter pylori range from asymptomatic gastritis to gastrointestinal malignancy. Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade B-cell marginal zone lymphoma and Helicobacter pylori has been detected in more than 75% of the patients with MALT lymphoma. Many tests for the detection of Helicobacter pylori are available, including antibody tests, urea breath tests, stool antigen tests and endoscopic biopsies. The eradication of Helicobacter pylori usually prevents the return of ulcers and ulcer complications even after appropriate medications such as PPIs are stopped. The eradication of Helicobacter pylori is important in the treatment of the rare condition of the stomach known as MALT lymphoma. The treatment of Helicobacter pylori to prevent stomach cancer is controversial. Confirmation of eradication is recommended in associated ulcers, persistent dyspepsia despite a test-and-treat approach, MALT lymphoma, and previous treatment for early-stage gastric cancer. The urea breath test and stool antigen test can be used to confirm the eradication and should be performed at least 4 weeks after the completion of therapy. Several diseases have been reported to be associated with Helicobacter pylori infection, including hematologic diseases, such as ITP, idiopathic iron deficiency anemia and vitamin B12 deficiency. There is a positive trend in the association between Helicobacter pylori infection and neurodegenerative disorders and new data showed a reduced risk of death due to stroke and lung cancer but an increased risk of preeclampsia in infected women, which requires further investigations. PMID:28616085
Shannon, C; Vickers, C; Field, A; Ward, R
The association between Helicobacter pylori infection and low grade mucosa-associated lymphoid tissue lymphoma is now widely accepted. In this report, we describe the concurrent development of Burkitt's lymphoma in the stomach of a 53-year-old male with perforated duodenal ulcer and positive H. pylori serology. The temporal relationship between these two events raises the possibility of a causal link between H. pylori infection and this lymphoproliferative disease. In describing this rare case of gastric Burkitt's lymphoma, we consider the evidence that supports this possibility.
Fox, J G
Early attempts to identify non-human reservoirs for Helicobacter pylori were largely unrewarding. The one exception being old-world macaques, which were found to be colonized with H. pylori; however, it is doubtful whether this species provides an important reservoir for human infection. The possibility of other animal reservoirs and zoonotic transmission of H. pylori has been discussed, but until recently has not received serious study. Enthusiasm to initiate extensive studies in this area were further dampened by the inability to experimentally infect several different species of mammals with the organism. Reports using whole-cell enzyme-linked immunoabsorbent assay (ELISA) sonicate to monitor infection serologically, have cited a high incidence of H. pylori infection in abattoir workers. These results have been criticized because of potential antigenic cross-reactivity in workers' sera due to the constant exposure of these personnel to other gastrointestinal flora of animals. The large spiral gastric Helicobacter-like organisms (GHLOs) commonly noted in dogs and cats are associated with approximately 0.08-1% of gastritis in humans. These GHLOs often infect patients who own pets, suggesting a zoonotic link. Thus, the recent isolation of H. pylori from the inflamed gastric mucosa of commercially reared cats, and the ability to experimentally infect cats with H. pylori, raises the possibility of zoonotic H. pylori transmission from infected animals who have close human contact. Water and raw vegetables have been linked with H. pylori transmission in a few epidemiologically-based studies in developing populations. The recent isolation of H. pylori from the faeces of adults and children implicates a faecal-oral transmission pathway and supports the theory that both food and water (via faecal contamination) could be a source of H. pylori. Providing conclusive evidence that H. pylori has the ability to exist in the environment as a viable, non-culturable coccoid form
Aspholm, Marina; Kalia, Awdhesh; Ruhl, Stefan; Schedin, Staffan; Arnqvist, Anna; Lindén, Sara; Sjöström, Rolf; Gerhard, Markus; Semino-Mora, Cristina; Dubois, Andre; Unemo, Magnus; Danielsson, Dan; Teneberg, Susann; Lee, Woo-Kon; Berg, Douglas E.; Borén, Thomas
Adherence of bacterial pathogens to host tissues contributes to colonization and virulence and typically involves specific interactions between bacterial proteins called adhesins and cognate oligosaccharide (glycan) or protein motifs in the host that are used as receptors. A given pathogen may have multiple adhesins, each specific for a different set of receptors and, potentially, with different roles in infection and disease. This chapter provides strategies for identifying and analyzing host glycan receptors and the bacterial adhesins that exploit them as receptors, with particular reference to adherence of the gastric pathogen Helicobacter pylori. PMID:17132512
Gisbert, Javier P
This article describes the main conclusions drawn from the presentations on Helicobacter pylori infection in Digestive Diseases Week, 2016. Despite the undeniable widespread reduction in the prevalence of this infection, infection rates continue to be high in developing countries. The prevalence of clarithromycin, metronidazole and quinolone resistance is markedly high in most countries and continues to rise. The management of H. pylori infection in patients with peptic ulcers still leaves much to be desired. Although H. pylori eradication reduces the incidence of gastric adenocarcinoma, it does not completely avoid its appearance. The new rapid stool antigen tests show promising results. The efficacy of standard triple therapy is clearly inadequate and continues to decline, and cannot therefore be recommended. Vonoprazan, when associated with 2 antibiotics, is more effective than traditional proton pump inhibitors, especially in clarithromycin-resistant patients. Non-bismuth quadruple (concomitant) therapy achieves eradication rates of around 90% and has a good safety profile. Concomitant therapy is more effective and simpler than sequential therapy. Although some probiotics can increase the efficacy and tolerability of triple therapy, the utility of its association with quadruple concomitant therapy has not been established. If a first treatment with clarithromycin fails, both bismuth-containing quadruple therapy and levofloxacin-containing triple therapy achieve good-but still suboptimal-results. The combination of bismuth and levofloxacin in the same regimen increases the efficacy of rescue therapy. The management of H. pylori infection by European gastroenterologists is widely heterogeneous and the eradication rates achieved by them are generally unacceptable. In Spain, the highest first-line eradication rate is obtained with quadruple concomitant therapy in 14-day regimens and with double doses of proton pump inhibitors; in second-line therapy, the use of
Caron, Tyler J; Scott, Kathleen E; Fox, James G; Hagen, Susan J
Long-term chronic infection with Helicobacter pylori (H. pylori) is a risk factor for gastric cancer development. In the multi-step process that leads to gastric cancer, tight junction dysfunction is thought to occur and serve as a risk factor by permitting the permeation of luminal contents across an otherwise tight mucosa. Mechanisms that regulate tight junction function and structure in the normal stomach, or dysfunction in the infected stomach, however, are largely unknown. Although conventional tight junction components are expressed in gastric epithelial cells, claudins regulate paracellular permeability and are likely the target of inflammation or H. pylori itself. There are 27 different claudin molecules, each with unique properties that render the mucosa an intact barrier that is permselective in a way that is consistent with cell physiology. Understanding the architecture of tight junctions in the normal stomach and then changes that occur during infection is important but challenging, because most of the reports that catalog claudin expression in gastric cancer pathogenesis are contradictory. Furthermore, the role of H. pylori virulence factors, such as cytotoxin-associated gene A and vacoulating cytotoxin, in regulating tight junction dysfunction during infection is inconsistent in different gastric cell lines and in vivo, likely because non-gastric epithelial cell cultures were initially used to unravel the details of their effects on the stomach. Hampering further study, as well, is the relative lack of cultured cell models that have tight junction claudins that are consistent with native tissues. This summary will review the current state of knowledge about gastric tight junctions, normally and in H. pylori infection, and make predictions about the consequences of claudin reorganization during H. pylori infection. PMID:26523106
O'Gara, E. A.; Hill, D. J.; Maslin, D. J.
Chronic Helicobacter pylori disease is reduced with Allium vegetable intake. This study was designed to assess the in vivo anti-H. pylori potential of a variety of garlic substances. The garlic materials all showed substantial but widely differing anti-H. pylori effects against all strains and isolates tested. The MICs (range, 8 to 32 μg/ml) and minimum bactericidal concentrations (MBCs) (range, 16 to 32 μg/ml) of undiluted garlic oil (GO) were smaller than those of garlic powder (GP) (MIC range, 250 to 500 μg/ml; MBC range, 250 to 500 μg/ml) but greater than the MIC of allicin (4.0 μg/ml) (Table 2) present in GP. Allicin (MIC, 6 μg/ml; MBC, 6 μg/ml) was more potent than diallyl disulfide (MIC range, 100 to 200 μg/ml; MBC range, 100 to 200 μg/ml), its corresponding sulfide, but of a strength similar to that of diallyl tetrasulfide (MIC range, 3 to 6 μg/ml; MBC range, 3 to 6 μg/ml). Antimicrobial activity of the diallyl sulfides increased with the number of sulfur atoms. Time course viability studies and microscopy showed dose-dependent anti-H. pylori effects with undiluted GO, GP, allicin, and diallyl trisulfide after a lag phase of ca. 1 to 2 h. Substantial in vitro anti-H. pylori effects of pure GO and GP and their diallyl sulfur components exist, suggesting their potential for in vivo clinical use against H. pylori infections. PMID:10788416
Olofsson, Annelie; Nygård Skalman, Lars; Obi, Ikenna; Lundmark, Richard
ABSTRACT Bacteria shed a diverse set of outer membrane vesicles that function as transport vehicles to deliver effector molecules and virulence factors to host cells. Helicobacter pylori is a gastric pathogen that infects half of the world’s population, and in some individuals the infection progresses into peptic ulcer disease or gastric cancer. Here we report that intact vesicles from H. pylori are internalized by clathrin-dependent endocytosis and further dynamin-dependent processes, as well as in a cholesterol-sensitive manner. We analyzed the uptake of H. pylori vesicles by gastric epithelial cells using a method that we refer to as quantification of internalized substances (qIS). The qIS assay is based on a near-infrared dye with a cleavable linker that enables the specific quantification of internalized substances after exposure to reducing conditions. Both chemical inhibition and RNA interference in combination with the qIS assay showed that H. pylori vesicles enter gastric epithelial cells via both clathrin-mediated endocytosis and additional endocytic processes that are dependent on dynamin. Confocal microscopy revealed that H. pylori vesicles colocalized with clathrin and dynamin II and with markers of subsequent endosomal and lysosomal trafficking. Interestingly, however, knockdown of components required for caveolae had no significant effect on internalization and knockdown of components required for clathrin-independent carrier (CLIC) endocytosis increased internalization of H. pylori vesicles. Furthermore, uptake of vesicles by both clathrin-dependent and -independent pathways was sensitive to depletion, but not sequestering, of cholesterol in the host cell membrane suggesting that membrane fluidity influences the efficiency of H. pylori vesicle uptake. PMID:24846379
Maubach, Gunter; Sokolova, Olga; Wolfien, Markus; Rothkötter, Hermann-Josef; Naumann, Michael
Helicobacter pylori, a class I carcinogen, induces a proinflammatory response by activating the transcription factor nuclear factor-kappa B (NF-κB) in gastric epithelial cells. This inflammatory condition could lead to chronic gastritis, which is epidemiologically and biologically linked to the development of gastric cancer. So far, there exists no clear knowledge on how H. pylori induces the NF-κB-mediated inflammatory response. In our study, we investigated the role of Ca(2+) /calmodulin-dependent kinase II (CAMKII), calmodulin, protein kinases C (PKCs) and the CARMA3-Bcl10-MALT1 (CBM) complex in conjunction with H. pylori-induced activation of NF-κB via the inhibitor of nuclear factor-kappa B kinase (IKK) complex. We use specific inhibitors and/or RNA interference to assess the contribution of these components. Our results show that CAMKII and calmodulin contribute to IKK complex activation and thus to the induction of NF-κB in response to H. pylori infection, but not in response to TNF-α. Thus, our findings are specific for H. pylori infected cells. Neither the PKCs α, δ, θ, nor the CBM complex itself is involved in the activation of NF-κB by H. pylori. The contribution of CAMKII and calmodulin, but not PKCs/CBM to the induction of an inflammatory response by H. pylori infection augment the understanding of the molecular mechanism involved and provide potential new disease markers for the diagnosis of gastric inflammatory diseases including gastric cancer.
Vetvickova, Jana; Fernandez-Botran, Rafael
Background Curcumin is a well-established natural molecule with significant biological and pharmaceutical effects. Its effects on Helicobacter pylori (H. pylori) infection have been repeatedly confirmed both in animal and human models. This study directly compared five different samples to evaluate if the effects are general or if they differ among samples. Methods Using a mouse model, we studied the effects of curcumin on lipid peroxide (LPO) level, myeloperoxidase (MPO) and urease activity, number of colonized bacteria, levels of anti-H. pylori antibodies, biofilm formation, IFN-γ, IL-4, gastrin and somatostatin levels in serum, and minimum inhibitory concentration. In addition, we evaluated the effects on biofilm production and antibacterial antibody response. Results In all tests, one sample (Sabinsa) was consistently the most active. Conclusions All curcumin samples showed some anti-H. pylori effects, but only some of the tested samples had significant activity. PMID:28149841
Graham, David Y; Dore, Maria Pina
SUMMARY Helicobacter pylori (H. Pylori) is a leading cause of gastroduodenal disease, including gastric cancer. H. pylori eradication therapies and their efficacy are summarized. A number of current treatment regimens will reliably yield >90% or 95% cure rates with susceptible strains. None has proven to be superior. We show how to predict the efficacy of a regimen in any population provided one knows the prevalence of antibiotic resistance. As with other infectious diseases, therapy should always be susceptibility-based. Susceptibility testing should be demanded. We provide recommendations for empiric therapies when the only option and describe how to distinguish studies providing misinformation from those providing reliable and interpretable data. When treated as an infectious disease, high H. pylori cure rates are relatively simple to reliably achieve. PMID:27077447
Mahachai, Varocha; Vilaichone, Ratha-Korn; Pittayanon, Rapat; Rojborwonwitaya, Jarin; Leelakusolvong, Somchai; Kositchaiwat, Chomsri; Mairiang, Pisaln; Praisontarangkul, Ong-Ard; Ovartlarnporn, Buncha; Sottisuporn, Jaksin; Pisespongsa, Pises; Maneerattanaporn, Monthira; Sony, Ravin; Sirinthornpunya, Siam; Chaiyamahapurk, Orawan; Wiwattanachang, Olarn; Sansak, Inchaya; Harnsomboon, Piyathida; Chitapanarux, Taned; Chuenrattanakul, Surapon
Management of Helicobacter pylori infection is an important aspect of many upper gastrointestinal tract diseases, such as chronic gastritis, peptic ulcer disease, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. The Thailand Consensus on H. pylori treatment 2015 consisted of 22 national experts who took active roles, discussed all important clinical information and investigated clinical aspects in four workshops, focuising on: (1) Diagnosis (2) Treatment (3) Follow-up after eradication and (4) H. pylori infection and special conditions. Experts were invited to participate on the basis of their expertise and contribution to H. pylori works and/or consensus methodology. The results of each workshop were taken to a final consensus vote by all experts. Recommendations were developed from the best evidence and availability to guide clinicians in management of this specific infection associated with variety of clinical outcomes.
De Luca, Concetta; Mancin, Annalisa; Calabrò, Maria; Daleno, Cristina; Ferrario, Antonella; Renzulli, Raffaella; Scuderi, Cristina; Casari, Erminia
We report a case of Helicobacter pylori transient bacteremia in a woman with ulcerated antral gastric cancer. The patient was hospitalized for laparoscopy and subtotal gastrectomy. After surgery she developed fever (39°C) and was empirically treated with levofloxacin. Blood cultures, collected and sent immediately to Laboratory, were positive for a spiral Gram-negative bacterium. This isolate was identified as H. pylori and the specific susceptibility test was performed. One day after the fever was decreased but antibiotic treatment with levofloxacin was continued and it was maintained until discharge. In summary, H. pylori transient bacteremia may occur as a rare complication after stomach surgery. Further studies are necessary to elucidate the potential role of Helicobacter pylori presence in blood.
Mentis, Andreas; Lehours, Philippe; Mégraud, Francis
During the period reviewed, prevalence studies were essentially performed in less economically advanced countries and a high prevalence was found. The traditional risk factors for Helicobacter pylori positivity were mostly found. Transmission studied by molecular typing showed a familial transmission. The eventual role of water transmission was explored in several studies with controversial results. Concerning diagnosis, most of the invasive and noninvasive methods used for the diagnosis of H. pylori infection are long standing with efficient performance. The most interesting recent improvements in H. pylori diagnosis include advances in endoscopy, developments in molecular methods, and the introduction of omics-based techniques. Interpretation of old or newer method should take into account the pretest probability and the prevalence of H. pylori in the population under investigation.
It is known that Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, and gastric carcinoma. Due to the increased side effects of the treatment regimens and the development of antimicrobial resistance, a number of natural compounds have been tested as potential alternatives. In this review, we will examine the current knowledge on the effect of Citrus fruits and their derivatives against H. pylori, highlighting the remaining outstanding questions on the development of novel therapeutic strategies. PMID:28408943
Segal, E D; Shon, J; Tompkins, L S
The association between Helicobacter pylori, gastritis, and peptic ulcer is well established, and the association of infection with gastric cancer has been noted in several developing countries. However, the pathogenic mechanism(s) leading to disease states has not been elucidated. The H. pylori urease is thought to be a determinant of pathogenicity, since the enzyme is produced by all H. pylori clinical isolates. Evidence indicates that some H. pylori strains are more cytotoxic than others, with a correlation between the activity of the urease and the presence of a vacuolating cytotoxin having been made. However, the number of cytotoxins remains unknown at this time. The relationship between the urease and cytotoxicity has previously been examined with chemical inhibitors. To examine the role of the urease and its relationship to cytotoxicity, urease-deficient mutants were produced following ethyl methanesulfonate mutagenesis of H. pylori 87A300. Two mutants (the ure1 and ure5 mutants) which were entirely deficient in urease activity (Ure-) were selected. Characterization of the isolates at the protein level showed that the urease subunits lacked the ability to complex and form the active urease enzyme. The ure1 mutant was shown to be sensitive to the effects of low pH in vitro and exhibited no cytotoxicity to eucaryotic cells, whereas the parental strain (Ure+) produced a cytotoxic effect in the presence of urea. Interaction between the H. pylori Ure+ and Ure- strains and Caco-2 cells appeared to be similar in that both bacterial types elicited pedestal formation and actin condensation. These results indicate that the H. pylori urease may have many functions, among them (i) protecting H. pylori against the acidic environment of the stomach, (ii) acting as a cytotoxin, with human gastric cells especially susceptible to its activity, and (iii) disrupting cell tight junctions in such a manner that the cells remain viable but an ionic flow between the cells occurs
Queiroz, D M; Mendes, E N; Rocha, G A
The use of a new indicator culture medium, Belo Horizonte medium, is proposed for better colony recognition and a presumptive identification of Campylobacter pylori. This medium, containing brain heart infusion sheep blood agar, was supplemented with 40 mg of 2,3,5-triphenyltetrazolium chloride per liter in addition to vancomycin, nalidixic acid, and amphotericin B. On Belo Horizonte medium, Campylobacter pylori present unique golden colonies. PMID:3429628
Helicobacter pylori (H. Pylori) is known as the most important cause of gastric cancer. The prevalence of H. pylori infection varies widely by geographic area, age, and socioeconomic status. In Japan, H. pylori infection has been highly correlated with the incidence rate of gastric cancer, and a reduction in H. pylori infection is therefore crucial for decreasing the incidence of gastric cancer, especially at the population level. Infection occurs during childhood, commonly before 5 years of age. In Japan, where gastric cancer has ranked as the most common cancer by incidence and mortality for the last several decades, the prevalence of H. pylori infection has dramatically declined by birth cohort effect, mainly due to improvements in the general hygiene environment in childhood. Older generations born before around 1950 show a high prevalence of around 80-90 %, decreasing with age to reach around 10 % or less in those born around the 1990s, and less than 2 % for children born after the year 2000. This change will have generational effects on gastric cancer prevention strategies, both primary and secondary. The risk-stratified approach to gastric cancer prevention should be considered in Japan and other countries which have similarly experienced rapid economic development.
Kennemann, Lynn; Didelot, Xavier; Aebischer, Toni; Kuhn, Stefanie; Drescher, Bernd; Droege, Marcus; Reinhardt, Richard; Correa, Pelayo; Meyer, Thomas F.; Josenhans, Christine; Suerbaum, Sebastian
High genetic diversity is a hallmark of the gastric pathogen Helicobacter pylori. We used 454 sequencing technology to perform whole-genome comparisons for five sets of H. pylori strains that had been sequentially cultured from four chronically infected Colombians (isolation intervals = 3–16 y) and one human volunteer experimentally infected with H. pylori as part of a vaccine trial. The four sets of genomes from Colombian H. pylori differed by 27–232 isolated SNPs and 16–441 imported clusters of polymorphisms resulting from recombination. Imports (mean length = 394 bp) were distributed nonrandomly over the chromosome and frequently occurred in groups, suggesting that H. pylori first takes up long DNA fragments, which subsequently become partially integrated in multiple shorter pieces. Imports were present at significantly increased frequency in members of the hop family of outer membrane gene paralogues, some of which are involved in bacterial adhesion, suggesting diversifying selection. No evidence of recombination and few other differences were identified in the strain pair from an infected volunteer, indicating that the H. pylori genome is stable in the absence of mixed infection. Among these few differences was an OFF/ON switch in the phase-variable adhesin gene hopZ, suggesting strong in vivo selection for this putative adhesin during early colonization. PMID:21383187
Craanen, M E; Blok, P; Dekker, W; Tytgat, G N
The relation between Helicobacter pylori, intestinal metaplasia, and early gastric cancer was studied by examining gastrectomy specimens from 31 intestinal type and 22 diffuse type carcinomas. A total of 298 patients with antral gastritis were used as controls. Atrophic changes and intestinal metaplasia were significantly more common in intestinal type early gastric cancer compared with diffuse type early gastric cancer (p < 0.05 and p < 0.001, respectively). H pylori was found in 61.3% of intestinal type early gastric cancer and in 54.5% of diffuse type early gastric cancer (NS). The age adjusted prevalence of intestinal metaplasia in the patients with antral gastritis was higher in H pylori positive patients in all age groups studied. Comparing gastritis patients with patients with intestinal type early gastric cancer showed the age adjusted prevalence of intestinal metaplasia to be significantly higher in the patients with early gastric cancer in all age groups studied. In conclusion, H pylori is associated with both types of early gastric carcinoma. Intestinal metaplasia formation seems to be a multifactorial process in which H pylori may play a part. These findings suggest that gastric cancer may be included in the spectrum of H pylori associated diseases, although many questions about causality remain to be answered. PMID:7959189
Shaikh, Kashif Hafeez; Ahmed, Suhaib; Ayyub, Muhammad; Anwar, Jaleel
To determine the association of Helicobacter pylori infection in patients presenting with idiopathic thrombocytopenic purpura (ITP). From March 2007 to March 2008, thirty adult patients with ITP and 30 age and sex matched healthy controls were investigated for the presence of H. pylori infection by Helicobacter pylori stool antigen (HpSA) an enzyme immunoassay (EIA) based method. The criteria for presence of H. pylori infection was a positive stool antigen test. H. pylori infection was found in 19 out of 30 patients with ITP (63.3%) which is well above the frequency of 13 out of 30 (43.3%) in controls. Calculated odds ratio was 2.25 which shows significant association of H. pylori infection with ITP. The study confirms the existence of an association between H. pylori infection and ITP. Therefore the screening for H. pylori infection and an attempt to eradicate bacterium in positive cases seems appropriate in patients with ITP at diagnosis.
Suzuki, H; Nomura, S; Masaoka, T; Goshima, H; Kamata, N; Kodama, Y; Ishii, H; Kitajima, M; Nomoto, K; Hibi, T
Recently, chicken egg yolk was recognized as an inexpensive antibody source, and the therapeutic usefulness of egg yolk immunoglobulin Y (IgY) in oral passive immunization has been investigated. Although multiple antibiotic treatments eradicate most Helicobacter pylori (H. pylori) infections, therapy fails in 10-15% of cases due to the development of drug resistance. Consequently, it is important that new, more broadly based therapies for the treatment of H. pylori infection should be identified. The present study evaluated the effect, on H. pylori infection, of IgY prepared from egg yolk of hens immunized with H. pylori urease (anti-HpU IgY). Seventeen asymptomatic volunteers diagnosed as H. pylori-positive by the 13C-urea breath test (UBT) were orally administered anti-HpU IgY for 4 weeks. Four weeks later, UBT values were significantly decreased although no case showed H. pylori eradication. An H. pylori-positive 53-year-old female gastritis patient administered anti-HpU IgY plus lansoprazole for 8 weeks showed a decrease in serum pepsinogen (PG) I and UBT values as well as an increase in the PG I/II ratio. In conclusion, anti-HpU IgY may mitigate H. pylori-associated gastritis and partially attenuate gastric urease activity. Furthermore, anti-HpU IgY combined with antacids appears to ameliorate gastric inflammation. These encouraging results may represent a novel approach to the management of H. pylori-associated gastroduodenal disease.
Francesco, Vincenzo De; Ierardi, Enzo; Hassan, Cesare; Zullo, Angelo
Some aspects related with the use of furazolidone as a rescue therapy for Helicobacter pylori (H pylori) infection should be remarked, especially regarding its potential oncologic risk. The inclusion of furazolidone in a treatment regimen for H pylori infection is, at least, controversial, and it does not appear to be safe. PMID:19370795
Kimura, A; Matsubasa, T; Kinoshita, H; Kuriya, N; Yamashita, Y; Fujisawa, T; Terakura, H; Shinohara, M
The objective of this study was to assess the prevalence of Helicobacter pylori seropositivity in institutionalized patients with severe neurologic impairment. Anti-H. pylori immunoglobulin G antibody in serum was measured in 196 institutionalized Japanese patients using enzyme linked immunosorbent assay, taking an antibody level >50 units/ml as evidence of H. pylori seropositivity. Patient age pattern and duration of institutionalization were examined for the relationships with H. pylori seropositivity. We also examined for seroconversion indicating new H. pylori infection in initially negative patients 1 year later. Positivity for H pylori infection among institutionalized patients was also compared with positivity among patients living at home. H. pylori seropositivity was present in 81.1% of subjects. Prevalence of H. pylori seropositivity increased with both age and duration of institutionalization. The serum level of anti-H. pylori immunoglobulin G antibody in patients over 20 years old was consistently high, approximately twice that of subjects less than 10 years of age. Of 38 patients initially negative for H. pylori infection, 18 (47.4%) had become positive at 1 year. H. pylori seropositivity was significantly more prevalent among institutionalized patients than among patients living at home (P < 0.0001). This study confirms that high H. pylori seropositivity rates are found among institutionalized patients with severe neurologic impairment. Our observations suggest person to person transmission, with fecal to oral, salivary secretion and respiratory droplet routes possibly being important pathways.
Helicobacter pylori has been shown to possess a very heterogeneous genoma despite its common phenotypic properties. Some characteristics relevant to pathogenesis have also been found to be heterogeneous. This is the case for adherence properties and the amount of urease produced, but it was not possible to relate these properties to disease entities. A vacuolating cytotoxin which alters epithelial cells has been found in about 60% of strains isolated from patients with ulcers versus 30% from those with gastritis only. The cagA gene can be used as a marker to detect the cag pathogenicity island. This DNA fragment seems to induce an increased inflammation in the gastric tissue via release of interleukin 8 by the epithelial cells. The association of this marker is strongly linked with ulcers compared with gastritis only (80% vs 55%, respectively). A number of other properties may be heterogeneous, but the low number of strains studied does not allow conclusions to be drawn.
Liu, Wei; Liu, Yu; Zhang, Xue-Zhi; Li, Ning; Cheng, Hong
To investigate the bactericidal effects of Jinghua Weikang Capsule and its major component Chenopodium ambrosioides L. on antibiotic-resistant Helicobacter pylori. Four clinical antibiotic-resistant H. pylori strains were isolated and incubated in liquid medium containing Jinghua Weikang Capsule or Chenopodium ambrosioides L. By means of time-kill curve method, the average colony counts and bactericidal rate were calculated at time points of 0, 4, 8 and 24 h after the incubation and the time-kill curves were charted. Both Jinghua Weikang Capsule and Chenopodium ambrosioides L. at a concentration of 0.64 g/L showed obvious bactericidal effect against antibiotic-resistant H. pylori after 4 h of incubation. Jinghua Weikang Capsule and Chenopodium ambrosioides L. are considered to be active against antibiotic-resistant H. pylori in vitro.
Ng, Garrett Z; Menheniott, Trevelyan R; Every, Alison L; Stent, Andrew; Judd, Louise M; Chionh, Yok Teng; Dhar, Poshmaal; Komen, Jasper C; Giraud, Andrew S; Wang, Timothy C; McGuckin, Michael A; Sutton, Philip
The mucin MUC1, best known for providing an epithelial barrier, is an important protective host factor in both humans and mice during Helicobacter pylori pathogenesis. This study aimed to identify the long-term consequences of MUC1 deficiency on H. pylori pathogenesis and the mechanism by which MUC1 protects against H. pylori gastritis. Wildtype and Muc1(-/-) mice were infected for up to 9 months, and the gastric pathology, immunological response and epigenetic changes assessed. The effects of MUC1 on the inflammasome, a potent inflammatory pathway, were examined in macrophages and H. pylori-infected mice deficient in both MUC1 and inflammasome components. Muc1(-/-) mice began to die 6 months after challenge, indicating Muc1 deficiency made H. pylori a lethal infection. Surprisingly, chimaeric mouse infections revealed MUC1 expression by haematopoietic-derived immune cells limits H. pylori-induced gastritis. Gastritis in infected Muc1(-/-) mice was associated with elevated interleukin (IL)-1β and epigenetic changes in their gastric mucosa similar to those in transgenic mice overexpressing gastric IL-1β, implicating MUC1 regulation of an inflammasome. In support of this, infected Muc1(-/-)Casp1(-/-) mice did not develop severe gastritis. Further, MUC1 regulated Nlrp3 expression via an nuclear factor (NF)-κB-dependent pathway and reduced NF-κB pathway activation via inhibition of IRAK4 phosphorylation. The importance of this regulation was proven using Muc1(-/-)Nlrp3(-/-) mice, which did not develop severe gastritis. MUC1 is an important, previously unidentified negative regulator of the NLRP3 inflammasome. H. pylori activation of the NLRP3 inflammasome is normally tightly regulated by MUC1, and loss of this critical regulation results in the development of severe pathology. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Richards, Crystal L.; Buchholz, Brittany J.; Ford, Timothy E.; Broadaway, Susan C.; Pyle, Barry H.; Camper, Anne K.
Helicobacter pylori is a Gram -negative bacterium that colonizes the human stomach and is responsible for causing gastric ulcers. H. pylori is known to become stressed and nonculturable after exposure to unfavorable conditions. In this study, we enhanced previously published resuscitation procedures, characterized conditions under which stressed H. pylori can be recovered, and formulated a selective and differential resuscitation medium. Results showed that a specialized broth supplemented with trace minerals and lysed human erythrocytes and serum is required for the recovery of nonculturable H. pylori. The type of stress was an important factor in the efficacy of resuscitation, with cells exposed to atmospheric oxygen more readily resuscitated than nutrient deprived cells. After resuscitation, culturable cells were recovered from previously nonculturable oxygen stressed cells (24 and 72 hours of exposure) and nonculturable nutrient deprived cells (24 hours of exposure). The length of time the cells were exposed to the stress was also an important factor in the recovery of stressed H. pylori. RNA levels were quantified and transcription of the cell division related gene, cdrA (HP0066), was assessed by qRT-PCR. The low levels of RNA detected in stressed cells, after resuscitation, support the idea that a small population of viable cells may be responsible for the colonies recovered on solid agar. The modification of the resuscitation broth into a selective and differential slant culture medium also allowed the recovery of stressed H. pylori. The methods presented here highlight the benefits and limitations of using human blood products for recovering nonculturable H. pylori. PMID:21129415
Khin, Mar Mar; Hua, Jie Song; Ng, Han Cong; Wadström, Torkel; Ho, Bow
AIM: To study the agglutination pattern of Helicobacter pylori coccoid and spiral forms. METHODS: Assays of agglutination and agglutination inhibition were applied using fifteen commercial lectins. RESULTS: Strong agglutination was observed with mannose-specific Concanavalin A (Con A), fucose-specific Tetragonolobus purpureas (Lotus A) and N-acetyl glucosamine-specific Triticum vulgaris (WGA) lectins. Mannose and fucose specific lectins were reactive with all strains of H. pylori coccoids as compared to the spirals. Specific carbohydrates, glycoproteins and mucin were shown to inhibit H. pylori lectin-agglutination reactions. Pre-treatment of the bacterial cells with formalin and sulphuric acid did not alter the agglutination patterns with lectins. However, sodium periodate treatment of bacterial cells were shown to inhibit agglutination reaction with Con A, Lotus A and WGA lectins. On the contrary, enzymatic treatment of coccoids and spirals did not show marked inhibition of H. pylori lectin agglutination. Interes tingly, heating of H. pylori cells at 60 °C for 1 h was shown to augment the agglutination with all of the lectins tested. CONCLUSION: The considerable differences in lectin agglutination patterns seen among the two differentiated forms of H. pylori might be attributable to the structural changes during the events of morphological transformation, resulting in exposing or masking some of the sugar residues on the cell surface. Possibility of various sugar residues on the cell wall of the coccoids may allow them to bind to different carbohydrate receptors on gastric mucus and epithelial cells. The coccoids with adherence characteristics like the spirals could aid in the pathogenic process of Helicobacter infection. This may probably lead to different clinical outcome of H. pylori associated gastroduodenal disease. PMID:11819557
Gunnarsdottir, Anna Ingibjorg; Gudjonsson, Hallgrimur; Hardardottir, Hjordis; Jonsdottir, Karen Drofn; Bjornsson, Einar Stefan
Increasing resistance of Helicobacter pylori (H. pylori) to antibiotics calls for constant re-evaluation of multidrug regimens that have been used to eradicate the infection. The aim of this study was to evaluate the current antibiotic susceptibility of H. pylori in an Icelandic cohort. Patients referred for gastroscopy were recruited prospectively. Those found to have a positive rapid urease test were included in the study. Susceptibility testing was conducted by the Epsilometer test (E-test) method for ampicillin, clarithromycin, levofloxacin, metronidazole and tetracycline. Results were obtained after three days of incubation in microaerophilic conditions at 37 °C, except for the metronidazole were the first 24 hours were anaerobic. Of the 613 patients who underwent gastroscopy, 138 (23%) had a positive rapid urease test. H. pylori was successfully cultured from 105 (76%) of the urease test positive patients and the isolates were tested for antibiotic susceptibility. Five patients had prior H. pylori eradication. Antibiotic resistance for ampicillin, clarithromycin, levofloxacin, metronidazole and tetracycline was 0%, 9%, 4%, 1% and 0%, respectively. If those who had previously undergone eradication treatment were excluded, the resistance was 0%, 6%, 3%, 1% and 0%, respectively. Clarithromycin resistance was higher amongst women than men, 13% vs. 5%, however, not significantly. Clarithromycin resistance was 60% amongst those who had previously received eradication treatment compared to 6% of those who had not (p < .0001). Clarithromycin resistance amongst the H. pylori isolates can be considered relatively low. Therefore, in the current cohort, standard triple-drug clarithromycin-containing regimen should remain the first-line treatment against H. pylori.
Handa, Osamu; Yoshida, Norimasa; Tanaka, Yukiko; Ueda, Miho; Ishikawa, Takeshi; Takagi, Tomohisa; Matsumoto, Naoyuki; Naito, Yuji; Yoshikawa, Toshikazu
Helicobacter pylori-infected gastrointestinal mucosa is frequently infiltrated by polymorphonuclear leukocytes (PMN) and monocytes, and these invading cells have been implicated in gastrointestinal mucosal inflammation. To clarify the efficacy of polaprezinc, a chelate compound consisting of zinc and L-carnosine, against H pylori-induced inflammation including PMN infiltration, the in vitro effects of this drug on interleukin (IL)-8 production by an established gastric cancer cell line (MKN 45 cells) and on PMN-endothelial cell adhesive interactions was investigated. Polaprezinc and zinc sulphate inhibited IL-8 production by MKN 45 cells in response to stimulation with H pylori water extract (HPE) in a dose-dependent manner from 10(-7) M to 10(-5) M. In addition, the expression of CD11b and CD18 on PMN and PMN-dependent adhesion to endothelial cells elicited by HPE was inhibited by polaprezinc and zinc sulphate in a concentration-dependent manner. L-carnosine did not have any effects on IL-8 production or PMN-endothelial cell interactions. These results suggest that polaprezinc, mainly the zinc component, may inhibit H pylori-induced PMN-mediated gastric inflammation by attenuating CD11b/CD18 expression on PMN and IL-8 production from gastric epithelial cells.
Álvarez-Arellano, Lourdes; Maldonado-Bernal, Carmen
The purpose of this paper is to review current information about the role of inflammation caused by Helicobacter pylori (H. pylori) infection in neurological diseases such as Parkinson’s disease, Alzheimer’s disease, Guillain-Barré syndrome, multiple sclerosis, and other inflammatory diseases including ischemic stroke. Infection with H. pylori usually persists throughout life, resulting in a chronic inflammatory response with local secretion of numerous inflammatory mediators including chemokines [interleukin (IL)-8, macrophage chemotactic protein (MCP)-1, growth-regulated oncogene (GRO)-α] and cytokines [IL-1β, tumor necrosis factor (TNF)-α, IL-6, IL-12, interferon (IFN)-γ], which can pass into the circulation and have a systemic effect. The persistence of detectable systemic and local concentrations of inflammatory mediators is likely to alter the outcome of neurological diseases. These proinflammatory factors can induce brain inflammation and the death of neurons and could eventually be associated to Parkinson’s disease and also may be involved in the development of Alzheimer’s disease. However, most neurological diseases are the result of a combination of multiple factors, but the systemic inflammatory response is a common component and determinant in the onset, evolution, and outcome of diseases. However, more studies are needed to allow understanding of the effects and mechanisms by which the inflammatory response generated by H. pylori infection affects neurological diseases. PMID:25400983
Santos, Rita S; Dakwar, George R; Xiong, Ranhua; Forier, Katrien; Remaut, Katrien; Stremersch, Stephan; Guimarães, Nuno; Fontenete, Sílvia; Wengel, Jesper; Leite, Marina; Figueiredo, Céu; De Smedt, Stefaan C; Braeckmans, Kevin; Azevedo, Nuno F
Helicobacter pylori infects more than 50% of the worldwide population. It is mostly found deep in the gastric mucus lining of the stomach, being a major cause of peptic ulcers and gastric adenocarcinoma. To face the increasing resistance of H. pylori to antibiotics, antimicrobial nucleic acid mimics are a promising alternative. In particular, locked nucleic acids (LNA)/2'-OMethyl RNA (2'OMe) have shown to specifically target H. pylori, as evidenced by in situ hybridization. The success of in vivo hybridization depends on the ability of these nucleic acids to penetrate the major physical barriers—the highly viscoelastic gastric mucus and the bacterial cell envelope. We found that LNA/2'OMe is capable of diffusing rapidly through native, undiluted, gastric mucus isolated from porcine stomachs, without degradation. Moreover, although LNA/2'OMe hybridization was still successful without permeabilization and fixation of the bacteria, which is normally part of in vitro studies, the ability of LNA/2'OMe to efficiently hybridize with H. pylori was hampered by the presence of mucus. Future research should focus on developing nanocarriers that shield LNA/2'OMe from components in the gastric mucus, while remaining capable of diffusing through the mucus and delivering these nucleic acid mimics directly into the bacteria. PMID:26645765
Allan, E; Clayton, C L; McLaren, A; Wallace, D M; Wren, B W
Helicobacter pylori is unique among bacterial pathogens in its ability to persist in the acidic environment of the human stomach. To identify H. pylori genes responsive to low pH, the authors assembled a high-density array of PCR-amplified random genomic DNA. Hybridization of radiolabelled cDNA probes, prepared using total RNA from bacteria exposed to buffer at either pH 4.0 or pH 7.0, allowed both qualitative and quantitative information on differential gene expression to be obtained. A previously described low-pH-induced gene, cagA, was identified together with several novel genes that may have relevance to the survival and persistence of H. pylori in the gastric environment. These include genes encoding enzymes involved in LPS and phospholipid synthesis and secF, encoding a component of the protein export machinery. A hypothetical protein unique to H. pylori (HP0681) was also found to be acid induced. Genes down-regulated at pH 4.0 include those encoding a sugar nucleotide biosynthesis protein, a flagellar protein and an outer-membrane protein. Differential gene expression was confirmed by total RNA slot-blot hybridization.
Gobert, Alain P.; Wilson, Keith T.
The innate immune response is a critical hallmark of Helicobacter pylori infection. Epithelial and myeloid cells produce effectors, including the chemokine CXCL8, reactive oxygen species (ROS), and nitric oxide (NO), in response to bacterial components. Mechanistic and epidemiologic studies have emphasized that dysregulated and persistent release of these products leads to the development of chronic inflammation and to the molecular and cellular events related to carcinogenesis. Moreover, investigations in H. pylori-infected patients about polymorphisms of the genes encoding CXCL8 and inducible NO synthase, and epigenetic control of the ROS-producing enzyme spermine oxidase, have further proven that overproduction of these molecules impacts the severity of gastric diseases. Lastly, the critical effect of the crosstalk between the human host and the infecting bacterium in determining the severity of H. pylori-related diseases has been supported by phylogenetic analysis of the human population and their H. pylori isolates in geographic areas with varying clinical and pathologic outcomes of the infection. PMID:28124148
Yeo, Se-Hwan; Yang, Chang-Hun
Although the global prevalence of peptic ulcer disease (PUD) is decreasing, PUD is still one of the most common upper gastrointestinal diseases in the world due to Helicobacter pylori infection and increased use of non-steroidal anti-inflammatory drugs. In Korea, the prevalence of H. pylori infection is also declining, but it is still the major cause of PUD. The outcomes of H. pylori infection are caused by imbalances between bacterial virulence factors, host factors, and environmental influences. In this review, we describe the prevalence trends of H. pylori infection in Korea, the mechanism of H. pylori infection-related PUD, and treatment strategies.
Wang, You-Hua; Lv, Zhi-Fa; Zhong, Yao; Liu, Dong-Sheng; Chen, Shu-Ping; Xie, Yong
Helicobacter pylori (H. pylori) internalization involves invasion of cells by the bacterium. Several studies have shown that H. pylori can invade human gastric epithelial cells, immune cells, and Candida yeast in vivo and in vitro. Whether bacterial invasion plays a role in eradication failure is unclear. To investigate the relationship between H. pylori invasion of GES-1 cells and H. pylori eradication failure. Forty-two clinical strains isolated from H. pylori-positive patients with different outcomes after treatment with furazolidone-based therapy were examined (17 failures and 25 successes). The H. pylori strains were shown to be susceptible to amoxicillin and furazolidone, and the patients also exhibited good compliance. Genotyping was performed for cagA and vacA (s and m). The antibiotic susceptibility of the strains to amoxicillin, furazolidone, clarithromycin, metronidazole, and levofloxacin was determined by E-tests. The levels of H. pylori invasion of GES-1 cells were detected by gentamicin colony-forming unit assays. The internalization level in the eradication success group was 5.40±5.78 × 10(-3) cfu/cell, and the median was 6.194 × 10(-3) cfu/cell; the internalization level in the eradication failure group was 8.98±5.40 × 10(-3) cfu/cell, and the median was 10.28 × 10(-3) cfu/cell. The eradication failure group showed a greater invasion level than the eradication success group (P<.05). No significant difference was observed between the susceptible strains and the resistant strains when the internalization levels were compared (P>.05). The results showed that H. pylori invasion of the gastric epithelia might play a role in eradication failure. © 2016 John Wiley & Sons Ltd.
Li, Hong; Liao, Tingting; Debowski, Aleksandra W; Tang, Hong; Nilsson, Hans-Olof; Stubbs, Keith A; Marshall, Barry J; Benghezal, Mohammed
This review covers the current knowledge and gaps in Helicobacter pylori lipopolysaccharide (LPS) structure and biosynthesis. H. pylori is a Gram-negative bacterium which colonizes the luminal surface of the human gastric epithelium. Both a constitutive alteration of the lipid A preventing TLR4 elicitation and host mimicry of the Lewis antigen decorated O-antigen of H. pylori LPS promote immune escape and chronic infection. To date, the complete structure of H. pylori LPS is not available, and the proposed model is a linear arrangement composed of the inner core defined as the hexa-saccharide (Kdo-LD-Hep-LD-Hep-DD-Hep-Gal-Glc), the outer core composed of a conserved trisaccharide (-GlcNAc-Fuc-DD-Hep-) linked to the third heptose of the inner core, the glucan, the heptan and a variable O-antigen, generally consisting of a poly-LacNAc decorated with Lewis antigens. Although the glycosyltransferases (GTs) responsible for the biosynthesis of the H. pylori O-antigen chains have been identified and characterized, there are many gaps in regard to the biosynthesis of the core LPS. These limitations warrant additional mutagenesis and structural studies to obtain the complete LPS structure and corresponding biosynthetic pathway of this important gastric bacterium. © 2016 John Wiley & Sons Ltd.
Lina, Taslima T; Alzahrani, Shatha; Gonzalez, Jazmin; Pinchuk, Irina V; Beswick, Ellen J; Reyes, Victor E
Helicobacter pylori (H. pylori) is perhaps the most ubiquitous and successful human pathogen, since it colonizes the stomach of more than half of humankind. Infection with this bacterium is commonly acquired during childhood. Once infected, people carry the bacteria for decades or even for life, if not treated. Persistent infection with this pathogen causes gastritis, peptic ulcer disease and is also strongly associated with the development of gastric cancer. Despite induction of innate and adaptive immune responses in the infected individual, the host is unable to clear the bacteria. One widely accepted hallmark of H. pylori is that it successfully and stealthily evades host defense mechanisms. Though the gastric mucosa is well protected against infection, H. pylori is able to reside under the mucus, attach to gastric epithelial cells and cause persistent infection by evading immune responses mediated by host. In this review, we discuss how H. pylori avoids innate and acquired immune response elements, uses gastric epithelial cells as mediators to manipulate host T cell responses and uses virulence factors to avoid adaptive immune responses by T cells to establish a persistent infection. We also discuss in this review how the genetic diversity of this pathogen helps for its survival. PMID:25278676
Kearney, David J; Hubbard, Todd; Putnam, David
Our aim was to define the utility of breath ammonia measurement in assessing Helicobacter pylori infection. Volunteers breathed into a device containing three fiberoptic NH3 sensors at baseline and after ingesting 300 mg of urea. Breath ammonia levels were compared to the [14C]urea breath test. Thirteen subjects were tested. Before urea ingestion, H. pylori-positive subjects had significantly lower breath ammonia levels than negative subjects (mean +/- SD, 0.04 ppm +/- 0.09 vs 0.49 ppm +/- 0.24, P = 0.002) and had a significantly greater increases in breath ammonia after urea ingestion (range 198-1,494% vs 6-98%). One H. pylori-positive subject underwent treatment and breath ammonia levels shifted from the pattern seen in positive subjects to that seen in negative subjects. In conclusion, breath ammonia measurement for H. Pylori-positive and negative subjects showed distinct patterns. Breath ammonia measurement may be feasible as a diagnostic test for H. pylori.
Moretti, Elena; Figura, Natale; Collodel, Giulia; Ponzetto, Antonio
Helicobacter pylori (H. pylori) infection could be associated with extra-digestive diseases. Here, we report the evidences concerning the decrease in reproductive potential occurring in individuals infected by H. pylori, especially by strains expressing CagA. This infection is more prevalent in individuals with fertility disorders. Infected women have anti-H. pylori antibodies in cervical mucus and follicular fluid that may decrease sperm motility and cross react immunologically with spermatozoa, conceivably hampering the oocyte/sperm fusion. Infection by CagA positive organisms enhances the risk of preeclampsia, which is a main cause of foetus death. These findings are supported by the results of experimental infections of pregnant mice, which may cause reabsorption of a high number of foetuses and alter the balance between Th1 and Th2 cell response. Infected men have decreased sperm motility, viability and numbers of normally shaped sperm and augmented systemic levels of inflammatory cytokines, such as tumor necrosis factor-α, which may damage spermatozoa. In countries where parasitic infestation is endemic, detrimental effects of infection upon spermatozoa may not occur, because the immune response to parasites could determine a switch from a predominant Th1 type to Th2 type lymphocytes, with production of anti-inflammatory cytokines. In conclusion, the evidences gathered until now should be taken into consideration for future studies aiming to explore the possible role of H. pylori infection on human reproduction.
Lina, Taslima T; Alzahrani, Shatha; Gonzalez, Jazmin; Pinchuk, Irina V; Beswick, Ellen J; Reyes, Victor E
Helicobacter pylori (H. pylori) is perhaps the most ubiquitous and successful human pathogen, since it colonizes the stomach of more than half of humankind. Infection with this bacterium is commonly acquired during childhood. Once infected, people carry the bacteria for decades or even for life, if not treated. Persistent infection with this pathogen causes gastritis, peptic ulcer disease and is also strongly associated with the development of gastric cancer. Despite induction of innate and adaptive immune responses in the infected individual, the host is unable to clear the bacteria. One widely accepted hallmark of H. pylori is that it successfully and stealthily evades host defense mechanisms. Though the gastric mucosa is well protected against infection, H. pylori is able to reside under the mucus, attach to gastric epithelial cells and cause persistent infection by evading immune responses mediated by host. In this review, we discuss how H. pylori avoids innate and acquired immune response elements, uses gastric epithelial cells as mediators to manipulate host T cell responses and uses virulence factors to avoid adaptive immune responses by T cells to establish a persistent infection. We also discuss in this review how the genetic diversity of this pathogen helps for its survival.
Moretti, Elena; Figura, Natale; Collodel, Giulia; Ponzetto, Antonio
Helicobacter pylori (H. pylori) infection could be associated with extra-digestive diseases. Here, we report the evidences concerning the decrease in reproductive potential occurring in individuals infected by H. pylori, especially by strains expressing CagA. This infection is more prevalent in individuals with fertility disorders. Infected women have anti-H. pylori antibodies in cervical mucus and follicular fluid that may decrease sperm motility and cross react immunologically with spermatozoa, conceivably hampering the oocyte/sperm fusion. Infection by CagA positive organisms enhances the risk of preeclampsia, which is a main cause of foetus death. These findings are supported by the results of experimental infections of pregnant mice, which may cause reabsorption of a high number of foetuses and alter the balance between Th1 and Th2 cell response. Infected men have decreased sperm motility, viability and numbers of normally shaped sperm and augmented systemic levels of inflammatory cytokines, such as tumor necrosis factor-α, which may damage spermatozoa. In countries where parasitic infestation is endemic, detrimental effects of infection upon spermatozoa may not occur, because the immune response to parasites could determine a switch from a predominant Th1 type to Th2 type lymphocytes, with production of anti-inflammatory cytokines. In conclusion, the evidences gathered until now should be taken into consideration for future studies aiming to explore the possible role of H. pylori infection on human reproduction. PMID:24914316
O'Rourke, Eyleen J.; Pinto, A. Viviana; Petroni, E. Alejandro; Tolmasky, Marcelo E.; Ielpi, Luis
Helicobacter pylori is a gram-negative bacterium that colonizes the human stomach, causes gastritis, and is associated with ulcers and gastric cancer. H. pylori is naturally competent for transformation. Natural genetic transformation is believed to be essential for the genetic plasticity observed in this species. While the relevance of horizontal gene transfer in H. pylori adaptiveness and antibiotic resistance is well documented, the DNA transformation machinery components are barely known. No enzymatic activity associated with the transformation process has been determined experimentally and described. We isolated, microsequenced, and cloned a major DNA nuclease from H. pylori. This protein, encoded by the open reading frame hp0323, was expressed in Escherichia coli. The purified protein, NucT, has a cation-independent thermostable nuclease activity that preferentially cleaves single-stranded DNA. NucT is associated with the membrane. NucT-deficient H. pylori strains are one or more orders of magnitude less efficient than the parental strain for transformation with either chromosomal or self-replicating plasmid DNA. To the best of our knowledge, NucT is the first nuclease identified in a gram-negative natural transformation system, and its existence suggests that there is a mechanism of DNA processing and uptake similar to the mechanisms in well-studied gram-positive systems. PMID:15090498
Zhang, Yuemiao; Gao, Wen; Cheng, Hong; Zhang, Xuezhi; Hu, Fulian
Eradication rate of Helicobacter pylori decreases worldwide, while antibiotics resistance rates of H. pylori increase rapidly in recent years. In most cases, H. pylori would be resistant to clarithromycin, metronidazole, and quinolone if these antibiotics had been used as component of eradication regimen. H. pylori strains resistant to both tetracycline and furazolidone are rare. The aim of our study was to evaluate efficacy and side effects of tetracycline- and furazolidone-containing quadruple regimen as rescue treatment. Patients with H. pylori infection given RTFB (rabeprazole 20 mg b.i.d. + tetracycline 750 mg b.i.d. +furazolidone 100 mg b.i.d. + colloidal bismuth subcitrate 200 mg b.i.d.) regimen for 14 days as rescue treatment were enrolled in this retrospective study. Eradication status was evaluated by (13) C-urea breath test, and side effects were collected. One hundred and nine patients were enrolled. The intention-to-treat eradication rate was 91.74% (100 of 109) and 95.24% (100 of 105) per protocol analysis. Side effects including fever, palpitation, and skin rash occurred in 35 patients. The 14-day tetracycline- and furazolidone-containing quadruple regimen can achieve a relatively high eradication rate as rescue treatment. Some side effects including fever may occur during the treatment. © 2014 John Wiley & Sons Ltd.
Bavi, Rohit; Kumar, Raj; Rampogu, Shailima; Son, Minky; Park, Chanin; Baek, Ayoung; Kim, Hyong-Ha; Suh, Jung-Keun; Park, Seok Ju; Lee, Keun Woo
Helicobacter pylori (H. pylori) persevere in the human stomach, an environment in which they encounter many DNA-damaging conditions, including gastric acidity. The pathogenicity of H. pylori is enhanced by its well-developed DNA repair mechanism, thought of as 'machinery,' such as nucleotide excision repair (NER). NER involves multi-enzymatic excinuclease proteins (UvrABC endonuclease), which repair damaged DNA in a sequential manner. UvrB is the central component in prokaryotic NER, essential for damage recognition. Therefore, molecular modeling studies of UvrB protein from H. pylori are carried out with homology modeling and molecular dynamics (MD) simulations. The results reveal that the predicted structure is bound to a DNA hairpin with 3-bp stem, an 11-nucleotide loop, and 3-nt 3' overhang. In addition, a mutation of the Y96A variant indicates reduction in the binding affinity for DNA. Free-energy calculations demonstrate the stability of the complex and help identify key residues in various interactions based on residue decomposition analysis. Stability comparative studies between wild type and mutant protein-DNA complexes indicate that the former is relatively more stable than the mutant form. This predicted model could also be useful in designing new inhibitors for UvrB protein, as well as preventing the pathogenesis of H. pylori.
Huynh, Hien Quoc; Couper, Richard T L; Tran, Cuong D; Moore, Lynette; Kelso, Richard; Butler, Ross N
N-Acetylcysteine (NAC), being both a mucolytic agent and a thiol-containing antioxidant, may affect the establishment and maintenance of H. pylori infection within the gastric mucus layer and mucosa. Agar and broth dilution susceptibility tests determined the MIC of H. pylori strain SSI to NAC. H. pylori load in SSI strain-infected C57BL mice was determined as colony forming units per gram of gastric tissue. Gastritis assessment was scored and gastric surface hydrophobicity was determined by contact angle measurement. MICs of NAC were 5 to 10 and 10 to 15 mg/ml using the agar dilution and broth dilution methods, respectively. NAC (120 mg per day for 14 days) reduced the H. pylori load in mice by almost 1 log compared with sham treatment. Pretreatment with NAC (40 mg/day) also significantly reduced the H. pylori load but did not prevent H. pylori colonization. Both H. pylori infection and NAC reduced the surface hydrophobicity of murine gastric mucosa. No significant differences were observed in the gastritis scores of H. felis- or H. pylori-infected mice receiving either NAC or sham treatments. This study demonstrates that NAC inhibits the growth of H. pylori in both agar and broth susceptibility tests and in H. pylori-infected mice. NAC did not alter the severity of H. pylori- or H. felis-induced gastritis.
Reshetnyak, Vasiliy Ivanovich; Reshetnyak, Tatiana Magomedalievna
Nearly half of the global population are carriers of Helicobacter pylori (H. pylori), a Gram-negative bacterium that persists in the healthy human stomach. H. pylori can be a pathogen and causes development of peptic ulcer disease in a certain state of the macroorganism. It is well established that H. pylori infection is the main cause of chronic gastritis and peptic ulcer disease (PUD). Decontamination of the gastric mucosa with various antibiotics leads to H. pylori elimination and longer remission in this disease. However, the reasons for repeated detection of H. pylori in recurrent PUD after its successful eradication remain unclear. The reason for the redetection of H. pylori in recurrent PUD can be either reinfection or ineffective anti-Helicobacter therapy. The administration of antibacterial drugs can lead not only to the emergence of resistant strains of microorganisms, but also contribute to the conversion of H. pylori into the resting (dormant) state. The dormant forms of H. pylori have been shown to play a potential role in the development of relapses of PUD. The paper discusses morphological H. pylori forms, such as S-shaped, C-shaped, U-shaped, and coccoid ones. The authors proposes the classification of H. pylori according to its morphological forms and viability.
Reshetnyak, Vasiliy Ivanovich; Reshetnyak, Tatiana Magomedalievna
Nearly half of the global population are carriers of Helicobacter pylori (H. pylori), a Gram-negative bacterium that persists in the healthy human stomach. H. pylori can be a pathogen and causes development of peptic ulcer disease in a certain state of the macroorganism. It is well established that H. pylori infection is the main cause of chronic gastritis and peptic ulcer disease (PUD). Decontamination of the gastric mucosa with various antibiotics leads to H. pylori elimination and longer remission in this disease. However, the reasons for repeated detection of H. pylori in recurrent PUD after its successful eradication remain unclear. The reason for the redetection of H. pylori in recurrent PUD can be either reinfection or ineffective anti-Helicobacter therapy. The administration of antibacterial drugs can lead not only to the emergence of resistant strains of microorganisms, but also contribute to the conversion of H. pylori into the resting (dormant) state. The dormant forms of H. pylori have been shown to play a potential role in the development of relapses of PUD. The paper discusses morphological H. pylori forms, such as S-shaped, C-shaped, U-shaped, and coccoid ones. The authors proposes the classification of H. pylori according to its morphological forms and viability. PMID:28785141
Jackman, R P; Schlichting, C; Carr, W; Dubois, A
Helicobacter pylori prevalence is elevated in German submarine crews and in United States Navy (USN) surface fleet personnel, but H. pylori prevalence in USN submariners was unknown. The goal of the study was to determine the prevalence of H. pylori in the crews of USN nuclear submarines compared to other military personnel and to the general US population. The presence of H. pylori IgG antibodies was determined in serum samples using a commercial ELISA. Only 47 out of 451 submariners (9.4%) were H. pylori positive, which is similar to that of the US general population with a similar level of education. In contrast, H. pylori prevalence is significantly higher in US Army recruits (26%), USN surface fleet personnel (25%), and German diesel submariners (38%). These data demonstrate that submarine service (and by inference activity requiring isolation and close contact, per se) is not a risk factor for H. pylori infection.
Klitorakis, I; Stanciu, C
The effect of Helicobacter pylori (H. pylori) on gastroesophageal reflux disease (GERD) is controversial. The aim of this study was to assess the relationship between H. pylori infection and symptoms of GERD. 112 patients (41 men, 71 women; mean 51 +/- 9.54 yeas, range 21-71 yeas) with symptomatic GERD were studied. The serologic evidence of H. pylori infection (IgG antibodies) was determined by means of ELISA ( enzyme-liked immunosorbent assay) in all patients. There were 59 (53.2%) patients infected with H. pylori. Statistical analysis did not reveal any significant different symptom scores between patients with and those without H. pylori infection. H. pylori infection plays no role on the development of GERD symptoms.
Kim, Eun Young; Kim, Ji Hyun; Woo, Saet Byul; Lee, Jeong Won; Lee, Kon Hee; Shin, Su Rin
The etiology of peptic ulcer disease in children may be primary, associated with Helicobacter pylori infection, or secondary, relied on underlying disease. Ulcerative lesions by H. pylori are mainly distributed in the duodenal bulb and they are rare below the ampulla of Vater because H. pylori growth is inhibited by bile juice. In this reason, there are only some restrictive reports presented small bowel ulcer associated H. pylori. We found multiple small bowel ulcerative lesions associated with H. pylori in an 11-year-old girl without any systemic disease while performing esophagogastroenteroscopy to the level of the proximal jejunum for differentiating bezoar. The abdominal pain improved after the patient was administered H. pylori eradication therapy. Because a small bowel ulcer associated with H. pylori has rarely been reported, we report it here with literature review. PMID:24010097
Tsugawa, Hitoshi; Suzuki, Hidekazu; Muraoka, Hiroe; Ikeda, Fumiaki; Hirata, Kenro; Matsuzaki, Juntaro; Saito, Yoshimasa; Hibi, Toshifumi
Although metronidazole (Mtz) is an important component of Helicobacter pylori eradication regimens, it has been pointed out that the increasing use of Mtz may result in increase in the incidence of Mtz-resistant strains. The present study was designed to examine the initial mechanism of resistance acquisition of H. pylori to Mtz. After 10 Mtz-susceptible strains were cultured on plates containing sub-inhibitory concentrations of Mtz, the MIC of Mtz for 9 of the 10 strains increased to levels of the Mtz-resistant strains. In the Mtz-resistance-induced strains, the expression of the TolC efflux pump (hefA) was significantly increased under Mtz exposure, without the reduction of the Mtz-reductive activity. Our finding suggests that overexpression of hefA may be the initial step in the acquisition of Mtz resistance in H. pylori. Copyright © 2010 Elsevier Inc. All rights reserved.
Correia, Marta; Casal, Susana; Vinagre, João; Seruca, Raquel; Figueiredo, Ceu; Touati, Eliette; Machado, José C
Helicobacter pylori colonizes half of the world population and is associated with gastric cancer. We have previously demonstrated that docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid known for its anti-inflammatory and antitumor effects, directly inhibits H. pylori growth in vitro and in mice. Nevertheless, the concentration of DHA shown to reduce H. pylori mice gastric colonization was ineffective in vitro. Related to the auxotrophy of H. pylori for cholesterol, we hypothesize that other mechanisms, in addition to DHA direct antibacterial effect, must be responsible for the reduction of the infection burden. In the present study we investigated if DHA affects also H. pylori growth, by reducing the availability of membrane cholesterol in the epithelial cell for H. pylori uptake. Levels of cholesterol in gastric epithelial cells and of cholesteryl glucosides in H. pylori were determined by thin layer chromatography and gas chromatography. The consequences of epithelial cells' cholesterol depletion on H. pylori growth were assessed in liquid cultures. We show that H. pylori uptakes cholesterol from epithelial cells. In addition, DHA lowers cholesterol levels in epithelial cells, decreases its de novo synthesis, leading to a lower synthesis of cholesteryl glucosides by H. pylori. A previous exposition of H. pylori to cholesterol influences the bacterium response to the direct inhibitory effect of DHA. Overall, our results suggest that a direct effect of DHA on H. pylori survival is modulated by its access to epithelial cell cholesterol, supporting the notion that cholesterol enhances the resistance of H. pylori. The cholesterol-dependent resistance of H. pylori to antimicrobial compounds raises new important aspects for the development of new anti-bacterial strategies.
Celli, Jonathan; Keates, Sarah; Kelly, Ciaran; Turner, Bradley; Bansil, Rama; Erramilli, Shyamsunder
It is well known that the viscoelastic properties of gastric mucin are crucial to the protection of the lining of the stomach against its own acidic secretions and other agents. Helicobacter Pylori, a rod shaped, gram-negative bacteria that dwells in the mucus layer of approximately 50% of the world's population is a class I carcinogen and is associated with gastric ulcers and severe gastritis. The structural damage to the mucus layer caused by H. Pylori is an important aspect of infection with this bacteria. We are examining the impact of H. Pylori on mucin and mucus rheology quantitatively using a combination of dynamic light scattering and multiple particle tracking experiments. Video microscopy data will also be presented on the motility of this bacteria in mucin at different pH and in other viscoelastic gels.
Mégraud, Francis; Lehours, Philippe
The discovery of Helicobacter pylori in 1982 was the starting point of a revolution concerning the concepts and management of gastroduodenal diseases. It is now well accepted that the most common stomach disease, peptic ulcer disease, is an infectious disease, and all consensus conferences agree that the causative agent, H. pylori, must be treated with antibiotics. Furthermore, the concept emerged that this bacterium could be the trigger of various malignant diseases of the stomach, and it is now a model for chronic bacterial infections causing cancer. Most of the many different techniques involved in diagnosis of H. pylori infection are performed in clinical microbiology laboratories. The aim of this article is to review the current status of these methods and their application, highlighting the important progress which has been made in the past decade. Both invasive and noninvasive techniques will be reviewed. PMID:17428887
Roesler, Bruna M.; Rabelo-Gonçalves, Elizabeth M.A.; Zeitune, José M.R.
Helicobacter pylori is a spiral-shaped Gram-negative bacterium that colonizes the human stomach and can establish a long-term infection of the gastric mucosa, a condition that affects the relative risk of developing various clinical disorders of the upper gastrointestinal tract, such as chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma. H. pylori presents a high-level of genetic diversity, which can be an important factor in its adaptation to the host stomach and also for the clinical outcome of infection. There are important H. pylori virulence factors that, along with host characteristics and the external environment, have been associated with the different occurrences of diseases. This review is aimed to analyzing and summarizing the main of them and possible associations with the clinical outcome. PMID:24833944
Yokota, K; Hirai, Y; Haque, M; Hayashi, S; Isogai, H; Sugiyama, T; Nagamachi, E; Tsukada, Y; Fujii, N; Oguma, K
The cells of Helicobacter pylori were suspended in the medium containing 35S-methionine. After a heat shock of the cells at 42 C for 5, 10, and 30 min, the production of proteins was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Out of many proteins produced by the cells, only 66 kDa protein production was dramatically increased by heat treatment. The N-terminal amino acid sequence of 66 kDa protein was quite similar to that of 62 kDa and 54 kDa proteins previously suggested as heat shock protein (HSP) of H. pylori based on the reaction with polyclonal and monoclonal antibodies against HSP 60 family proteins produced by other bacteria. Therefore, it was concluded that H. pylori produces the 66 kDa protein as its major heat shock protein which belongs to HSP 60 family.
Agarwal, Kanishtha; Agarwal, Shvetank
Helicobacter pylori infection is highly prevalent worldwide and is an important cause of gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma (MALToma), and gastric adenocarcinoma. Infection is usually acquired during childhood and tends to persist unless treated. Because eradication requires treatment with multidrug regimens, prevention of initial infection by a suitable vaccine is attractive. Although immunization with H pylori protein subunits has been encouraging in animals, similar vaccine trials in humans have shown adjuvant-related adverse effects and only moderate effectiveness. Newer immunization approaches (use of DNA, live vectors, bacterial ghosts, and microspheres) are being developed. Several questions about when and whom to vaccinate will need to be appropriately answered, and a cost-effective vaccine production and delivery strategy will have to be useful for developing countries. For this review, we searched MEDLINE using the Medical Subject Heading (MeSH) terms Helicobacter pylori and vaccines for articles in English from 1990 to 2007.
Berthenet, Elvire; Sheppard, Sam; Vale, Filipa F
The development of high-throughput whole genome sequencing (WGS) technologies is changing the face of microbiology, facilitating the comparison of large numbers of genomes from different lineages of a same organism. Our aim was to review the main advances on Helicobacter pylori "omics" and to understand how this is improving our knowledge of the biology, diversity and pathogenesis of H. pylori. Since the first H. pylori isolate was sequenced in 1997, 510 genomes have been deposited in the NCBI archive, providing a basis for improved understanding of the epidemiology and evolution of this important pathogen. This review focuses on works published between April 2015 and March 2016. Helicobacter "omics" is already making an impact and is a growing research field. Ultimately these advances will be translated into a routine clinical laboratory setting in order to improve public health.
Allen, Lee-Ann H
Helicobacter pylori is a Gram-negative bacterium that colonizes the gastric epithelium and plays a causative role in the development of peptic ulcers and gastric cancer. Phagocytosis is an element of innate defense used by macrophages and neutrophils to engulf microorganisms. We and others have shown that strains of H. pylori that contain the cag pathogenicity island actively retard their entry into phagocytes. Consequently, there is a lag of several minutes between bacterial binding and the onset of engulfment, and relative to other particles and microbes, the rate of internalization is slow. Herein, we describe in detail the use of synchronized phagocytosis and indirect immunofluorescence microscopy to quantify the rate and extent of H. pylori phagocytosis. This method is appropriate for primary phagocytes as well as transformed cell lines. More importantly, the effects of opsonins, virulence factors, and other agents on infection can be measured independent of bacterial viability or intracellular locale.
Sánchez-Zauco, Norma Angélica; Torres, Javier; Pérez-Figueroa, Gloria Erandi; Álvarez-Arellano, Lourdes; Camorlinga-Ponce, Margarita; Gómez, Alejandro; Giono-Cerezo, Silvia; Maldonado-Bernal, Carmen
Helicobacter pylori contains a pathogenicity island, cagPAI, with genes homologous to components of the type IV secretion system (T4SS) of Agrobacterium tumefaciens. The T4SS components assemble a structure that transfers CagA protein and peptidoglycan into host epithelial cells, causing the increased release of interleukin 8 (IL8) from the cells. The Toll-like receptors on neutrophils recognize H. pylori, initiating signaling pathways that enhance the activation of NF-κB. However, the roles of cagPAI and T4SS in the inflammatory response of neutrophils are unknown. We evaluated the participation of cagPAI and T4SS in the response of human neutrophils to H. pylori infection. Neutrophils were isolated from the blood of healthy donors and infected with H. pylori cagPAI+, cagPAI–, and cagPAI mutant strains virB4– and virD4–. Whereas cagPAI+ strain 26695 induced the greatest IL8 production, a proinflammatory response, cagPAI– strain 8822 induced the greatest IL10 production, an anti-inflammatory response. In contrast, the virB4– and virD4– mutant strains produced significantly more of the two proinflammatory cytokines IL1β and tumor necrosis factor αthan the cagPAI+ strain 26695. We observed that H. pylori downregulated the expression of TLRs 2 and 5 but upregulated TLR9 expression in a cagPAI and T4SS-independent manner. These results show for the first time that the response of human neutrophils to H. pylori may vary from a pro-inflammatory to an anti-inflammatory response, depending on cagPAI and the integrity of T4SS. PMID:23755130
Bury-Moné, Stéphanie; Thiberge, Jean-Michel; Contreras, Monica; Maitournam, Aboubakar; Labigne, Agnès; De Reuse, Hilde
The virulence of pathogenic bacteria is dependent on their adaptation to and survival in the stressful conditions encountered in their hosts. Helicobacter pylori exclusively colonizes the acid stomach of primates, making it an ideal study model. Little is known about how H. pylori responds to the moderately acidic conditions encountered at its colonization site, the gastric mucus layer. Thus, we compared gene expression profiles of H. pylori 26695 grown at neutral and acidic pH, and validated the data for a selection of genes by real-time polymerase chain reaction, dot-blots or enzymatic assays. During growth in acidic conditions, 56 genes were upregulated and 45 genes downregulated. We found that acidity is a signal modulating the expression of several virulence factors. Regulation of genes related to metal ion homeostasis suggests protective mechanisms involving diminished transport and enhanced storage. Genes encoding subunits of the F0F1 ATPase and of a newly identified Na+/H+ antiporter (NhaC-HP0946) were downregulated, revealing that this bacterium uses original mechanisms to control proton entry. Five of the upregulated genes encoded proteins controlling intracellular ammonia synthesis, including urease, amidase and formamidase, underlining the major role of this buffering compound in the protection against acidity in H. pylori. Regulatory networks and transcriptome analysis as well as enzymatic assays implicated two metal-responsive transcriptional regulators (NikR and Fur) and an essential two-component response regulator (HP0166, OmpR-like) as effectors of the H. pylori acid response. Finally, a nikR-fur mutant is attenuated in the mouse model, emphasizing the link between response to acidity, metal metabolism and virulence in this gastric pathogen.
Miftahussurur, Muhammad; Sharma, Rabi Prakash; Shrestha, Pradeep Krishna; Suzuki, Rumiko; Uchida, Tomohisa; Yamaoka, Yoshio
Prevalence of Helicobacter pylori infection in Nepal, a low-risk country for gastric cancer, is debatable. To our knowledge, no studies have examined H. pylori virulence factors in Nepal. We determined the prevalence of H. pylori infection by using three different tests, and the genotypes of virulence factors were determined by PCR followed by sequencing. Multilocus sequence typing was used to analyze the population structure of the Nepalese strains. The prevalence of H. pylori infection in dyspeptic patients was 38.4% (56/146), and was significantly related with source of drinking water. In total, 51 strains were isolated and all were cagA-positive. Western-type-cagA (94.1%), cagA pre-EPIYA type with no deletion (92.2%), vacA s1a (74.5%), and m1c (54.9%) were the predominant genotypes. Antral mucosal atrophy levels were significantly higher in patients infected with vacA s1 than in those infected with s2 genotypes (P = 0.03). Several Nepalese strains were H. pylori recombinants with genetic features of South Asian and East Asian genotypes. These included all East-Asian-type-cagA strains, with significantly lesser activity and inflammation in the corpus than the strains of the specific South Asian genotype (P = 0.03 and P = 0.005, respectively). Although the population structure confirmed that most Nepalese strains belonged to the hpAsia2 population, some strains shared hpEurope- and Nepalese-specific components. Nepalese patients infected with strains belonging to hpEurope showed higher inflammation in the antrum than strains from the Nepalese specific population (P = 0.05). These results support that ancestor roots of Kathmandu`s people not only connected with India alone. PMID:26226153
Hu, L T; Mobley, H L
The genes encoding Helicobacter pylori urease, a nickel metalloenzyme, have been cloned and expressed in Escherichia coli. Enzymatic activity, however, has been very weak compared with that in clinical isolates of H. pylori. Conditions under which near wild-type urease activity was achieved were developed. E. coli. SE5000 containing recombinant H. pylori urease genes was grown in minimal medium containing no amino acids, NiCl2 was added to 0.75 microM, and structural genes ureA and ureB (pHP902) were overexpressed in trans to the complete urease gene cluster (pHP808). Under these conditions, E. coli SE5000 pHP808/pHP902) expressed a urease activity up to 87 mumol of urea per min per mg of protein (87 U/mg of protein), a level approaching that of wild-type H. pylori UMAB41 (100 U/mg of protein), from which the genes were cloned. Poor catalytic activity of recombinant clones grown in Luria broth or M9 medium containing 0.5% Casamino Acids was due to chelation of nickel ions by medium components, particularly histidine and cysteine. In cultures containing these amino acids, 63Ni2+ was prevented from being transported into cells and was not incorporated into urease protein. As a consequence, M9 minimal medium cultures containing histidine or cysteine produced only 0.05 and 0.9%, respectively, of active urease produced by control cultures containing no amino acids. We conclude that recombinant H. pylori urease is optimally expressed when Ni2+ transport is not inhibited and when sufficient synthesis of urease subunits UreA and UreB is provided. Images PMID:8500893
Irani, Soussan; Monsef Esfahani, Alireza; Bidari Zerehpoush, Farahnaz
Background and aims. Helicobacter pylori is a microaerophilic gram-negative spiral organism. It is recognized as the etiologic factor for peptic ulcers, gastric adenocarcinoma and gastric lymphoma. Recently, it has been isolated from dental plaque and the dorsum of the tongue. This study was designed to assess the association between H. pylori and oral lesions such as ulcerative/inflammatory lesions, squamous cell carcinoma (SCC) and primary lymphoma. Materials and methods. A total of 228 biopsies diagnosed as oral ulcerative/inflammatory lesions, oral squamous cell carcinoma (OSCC) and oral primary lymphoma were selected from the archives of the Pathology Department. Thirty-two samples that were diagnosed as being without any pathological changes were selected as the control group. All the paraffin blocks were cut for hematoxylin and eosin staining to confirm the diagnoses and then the samples were prepared for immunohistochemistry staining. Data were collected and analyzed. Results. Chi-squared test showed significant differences between the frequency of H. pylori positivity in normal tissue and the lesions were examined (P=0.000). In addition, there was a statistically significant difference between the lesions examined (P=0.042). Chi-squared test showed significant differences between H. pylori positivity and different tissue types except inside the muscle layer as follows: in epithelium and in lamina propria (P=0.000), inside the blood vessels (P=0.003), inside the salivary gland duct (P=0.036), and muscle layer (P=0.122). Conclusion. There might be a relation between the presence of H. pylori and oral lesions. Therefore, early detection and eradication of H. pylori in high-risk patients are suggested. PMID:24578822
Herndon, Betty L; Vlach, Victoria; Dew, Michelle; Willsie, Sandra K
The purpose of this study was to determine serum antibody titers against a common bacterial antigen, Helicobacter pylori (H. pylon), in subjects with sarcoidosis, comparing those titers to those present in a healthy population. With the approval of the Institutional Review Board of the University of Missouri-Kansas City, patients with sarcoidosis (pulmonary and extrapulmonary) who visited the Truman Medical Center-Hospital Hill pulmonary clinic were recruited to enter the study. A serum sample was frozen at -70 degrees C for later testing (n = 20). Specific information collected on subjects included corticosteroid use, use of histamine2 blockers and antacids, date of first diagnosis, and stage of sarcoidosis. Normal controls and demographically matched individuals who lacked pulmonary diseases, including sarcoidosis, were also recruited. Serum samples were processed as above. Antibody capture enzyme immunoassay was completed for H. pylori and urease antigens by serum dilution assay for each subject, from which titers for antigen-specific immunoglobulin (Ig)G and IgA were calculated. Nonspecific serum IgE was also measured. An increased incidence of high-titer IgG antibody directed against H. pylori antigens was found in subjects with sarcoidosis compared with controls. The sarcoidosis and control groups were significantly different with respect to IgG and IgA against H. pylori, both at p = .001. IgG directed against urease was also significantly different between sarcoidosis and control patients (p = .001), but IgA directed against urease was very low in all subjects and did not yield significant differences between groups. Specific H. pylori and urease IgG antibodies exceeded those expected in the population studied. The data suggest that in pulmonary sarcoidosis, the relationship of H. pylori and its products to sarcoid granuloma formation warrants further investigation.
Pasternak, H I
Helicobacter pylori infection continues to be one of the hottest topics in gastroenterology, challenging the primary care physician daily with the clinical application of its new developments and frequency of involvement in differential diagnosis. This article offers the primary care physician a practical approach to the dyspeptic office patient that emphasizes the differential diagnosis of H pylori. Included is a strategy for rapid patient evaluation through key questions in the history, simple maneuvers in the physical examination, and a logical approach to testing and therapy based on the latest literature. The recommendations for all these office-based steps are designed to be efficient, cost-effective, and clinically relevant.
Cârdei, E; Moraru, D; Trandafir, Laura; Bozomitu, Laura; Mihăilă, Doina
Celiac disease, also known as gluten-sensitive enteropathy, is an autoimmune enteropathy caused by the ingestion of gluten-containing grains in susceptible subjects. The authors present a 3 years and 5 months old girl diagnosed with celiac disease at 1 year and 5 months old. Initially, the evolution after gluten-free diet was favorable. After 2 years the child presented abdominal pain and anorexia. The IgA antigliadin antibodies had normal values. The gastric biopsy found Helicobacter pylori gastritis. After treatment for Helicobacter pylori eradication the symptoms disappeared.
Makobongo, Morris O.; Gancz, Hanan; Carpenter, Beth M.; McDaniel, Dennis P.
Helicobacter pylori has developed antimicrobial resistance to virtually all current antibiotics. Thus, there is a pressing need to develop new anti-H. pylori therapies. We recently described a novel oligo-acyl-lysyl (OAK) antimicrobial peptidomimetic, C12K-2β12, that shows potent in vitro bactericidal activity against H. pylori. Herein, we define the mechanism of action and evaluate the in vivo efficacy of C12K-2β12 against H. pylori after experimental infection of Mongolian gerbils. We demonstrate using a 1-N-phenylnaphthylamine (fluorescent probe) uptake assay and electron microscopy that C12K-2β12 rapidly permeabilizes the bacterial membrane and creates pores that cause bacterial cell lysis. Furthermore, using nucleic acid binding assays, Western blots, and confocal microscopy, we show that C12K-2β12 can cross the bacterial membranes into the cytoplasm and tightly bind to bacterial DNA, RNA, and proteins, a property that may result in inhibition of enzymatic activities and macromolecule synthesis. To define the in vivo efficacy of C12K-2β12, H. pylori-infected gerbils were orogastrically treated with increasing doses and concentrations of C12K-2β12 1 day or 1 week postinfection. The efficacy of C12K-2β12 was strongest in animals that received the largest number of doses at the highest concentration, indicating dose-dependent activity of the peptide (P < 0.001 by analysis of variance [ANOVA]) regardless of the timing of the treatment with C12K-2β12. Overall, our results demonstrate a dual mode of action of C12K-2β12 against the H. pylori membrane and cytoplasmic components. Moreover, and consistent with the previously reported in vitro efficacy, C12K-2β12 shows significant in vivo efficacy against H. pylori when used as monotherapy. Therefore, OAK peptides may be a valuable resource for therapeutic treatment of H. pylori infection. PMID:22064541
Yu, Xiao-Dan; Zheng, Rong-Bo; Xie, Jian-Hui; Su, Ji-Yan; Huang, Xiao-Qi; Wang, Yong-Hong; Zheng, Yi-Feng; Mo, Zhi-Zhun; Wu, Xiao-Li; Wu, Dian-Wei; Liang, Ye-er; Zeng, Hui-Fang; Su, Zi-Ren; Huang, Ping
Baicalin and scutellarin are the principal bioactive components of Scutellaria baicalensis Georgi which has extensively been incorporated into heat-clearing and detoxification formulas for the treatment of Helicobacter pylori-related gastrointestinal disorders in traditional Chinese medicine. However, the mechanism of action remained to be defined. To explore the inhibitory effect, kinetics and mechanism of Helicobacter pylori urease (the vital pathogenetic factor for Helicobacter pylori infection) inhibition by baicalin and scutellarin, for their therapeutic potential. The ammonia formations, indicator of urease activity, were examined using modified spectrophotometric Berthelot (phenol-hypochlorite) method. The inhibitory effect of baicalin and scutellarin was characterized with IC50 values, compared to acetohydroxamic acid (AHA), a well known Helicobacter pylori urease inhibitor. Lineweaver-Burk and Dixon plots for the Helicobacter pylori urease inhibition of baicalin and scutellarin was constructed from the kinetic data. SH-blocking reagents and competitive active site Ni(2+) binding inhibitors were employed for mechanism study. Molecular docking technique was used to provide some information on binding conformations as well as confirm the inhibition mode. Moreover, cytotoxicity experiment using Gastric Epithelial Cells (GES-1) was evaluated. Baicalin and scutellarin effectively suppressed Helicobacter pylori urease in dose-dependent and time-independent manner with IC50 of 0.82±0.07 mM and 0.47±0.04 mM, respectively, compared to AHA (IC50=0.14±0.05 mM). Structure-activity relationship disclosed 4'-hydroxyl gave flavones an advantage to binding with Helicobacter pylori urease. Kinetic analysis revealed that the types of inhibition were non-competitive and reversible with inhibition constant Ki of 0.14±0.01 mM and 0.18±0.02 mM for baicalin and scutellarin, respectively. The mechanism of urease inhibition was considered to be blockage of the SH groups of
Helicobacter pylori (H. pylori) infection with its vast prevalence is responsible for various gastric diseases including gastritis, peptic ulcers, and gastric malignancy. While effective, current treatment regimens are challenged by a fast-declining eradication rate due to the increasing emergence of H. pylori strains resistant to existing antibiotics. Therefore, there is an urgent need to develop novel antibacterial strategies against H. pylori. The first area of this research, we developed a liposomal nanoformulation of linolenic acid (LipoLLA) and evaluated its bactericidal activity against resistant strains of H. pylori. We found that LipoLLA was effective in killing both spiral and dormant forms of the bacteria via disrupting bacterial membranes. LipoLLA eradicated all strains of the bacteria regardless of their antibiotic resistance status. Furthermore, the bacteria did not develop drug resistance toward LipoLLA. Our findings suggest that LipoLLA is a promising antibacterial nanotherapeutic to treat antibiotic-resistant H. pylori infection. The next step, we investigated the in vivo therapeutic potential of LipoLLA for the treatment of H. pylori infection. In vivo tests further confirmed that LipoLLA was able to kill H. pylori and reduce bacterial load in the mouse stomach. LipoLLA treatment was also shown to reduce the levels of proinflammatory cytokines including interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor alpha, which were otherwise elevated due to the H. pylori infection. Finally, toxicity test demonstrated excellent biocompatibility of LipoLLA to normal mouse stomach. Collectively, results from this work indicate that LipoLLA is a promising, new, effective, and safe therapeutic agent for the treatment of H. pylori infection. The second area is stimuli-responsive liposomes development. By adsorbing small chitosan-modified gold nanoparticles (AuChi) onto the outer surface of liposomes, we show that at gastric pH the liposomes have
Talebi Bezmin Abadi, Amin; Perez-Perez, Guillermo
Helicobacter pylori (H. pylori) is a gastric human pathogen associated with acute and chronic gastritis, 70% of all gastric ulcers, 85% of all duodenal ulcers, and both forms of stomach cancer, mucosal-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Recently, attention has focused on possible relationship between presence of certain virulence factor and H. pylori-associated diseases. Some contradictory data between this bacterium and related disorders has been observed since not all the colonized individuals develop to severe disease. The reported diseases plausibility related to H. pylori specific virulence factors became an interesting story about this organism. Although a number of putative virulence factors have been identified including cytotoxin-associated gene a (cagA) and vacA, there are conflicting data about their actual participation as specific risk factor for H. pylori-related diseases. Duodenal ulcer promoting gene a (dupA) is a virulence factor of H. pylori that is highly associated with duodenal ulcer development and reduced risk of gastric cancer. The prevalence of dupA in H. pylori strains isolated from western countries is relatively higher than in H. pylori strains from Asian countries. Current confusing epidemiological reports will continue unless future sophisticated and molecular studies provide data on functional and complete dupA cluster in H. pylori infected individuals. This paper elucidates available knowledge concerning role of dupA in virulence of H. pylori after a decade of its discovery.
Talebi Bezmin Abadi, Amin; Perez-Perez, Guillermo
Helicobacter pylori (H. pylori) is a gastric human pathogen associated with acute and chronic gastritis, 70% of all gastric ulcers, 85% of all duodenal ulcers, and both forms of stomach cancer, mucosal-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Recently, attention has focused on possible relationship between presence of certain virulence factor and H. pylori-associated diseases. Some contradictory data between this bacterium and related disorders has been observed since not all the colonized individuals develop to severe disease. The reported diseases plausibility related to H. pylori specific virulence factors became an interesting story about this organism. Although a number of putative virulence factors have been identified including cytotoxin-associated gene a (cagA) and vacA, there are conflicting data about their actual participation as specific risk factor for H. pylori-related diseases. Duodenal ulcer promoting gene a (dupA) is a virulence factor of H. pylori that is highly associated with duodenal ulcer development and reduced risk of gastric cancer. The prevalence of dupA in H. pylori strains isolated from western countries is relatively higher than in H. pylori strains from Asian countries. Current confusing epidemiological reports will continue unless future sophisticated and molecular studies provide data on functional and complete dupA cluster in H. pylori infected individuals. This paper elucidates available knowledge concerning role of dupA in virulence of H. pylori after a decade of its discovery. PMID:28028359
Hulten, K; Han, S W; Enroth, H; Klein, P D; Opekun, A R; Gilman, R H; Evans, D G; Engstrand, L; Graham, D Y; El-Zaatari, F A
An association between water sources and the prevalence of Helicobacter pylori infection in Peruvian children was shown previously. The aim of this study was to confirm the presence of H. pylori in drinking water in the same community. Forty-eight drinking water samples from different locations in pueblo jovenes (new towns) near Lima were collected. Samples were frozen until technology advanced to the point to the point at which H. pylori might be reliably detected. Immunomagnetic beads coated with anti-H. pylori immunoglobulin Gs were used to concentrate H. pylori, and two polymerase chain reaction assays based on different H. pylori genes were used. One was a polymerase chain reaction for the detection of the H. pylori adhesin subunit encoding gene, and the second was a previously validated H. pylori 16S ribosomal RNA reverse transcriptase-polymerase chain reaction. The expected 375-base pair fragment from the adhesin gene was amplified from 24 water samples. The expected 500-base pair fragment of the 16S ribosomal RNA and the 375-base pair fragment of the adhesin gene were amplified from 11 of the samples. These results confirm the presence of H. pylori in drinking water in Peru and are consistent with conclusions from a previous epidemiological study of the same population. This provides additional evidence for waterborne transmission of H. pylori in some environments.
Cui, Rongli; Zhou, Liya
This article aimed to review the incidence of Helicobacter pylori (H. pylori) infection and its therapy. Relevant articles published in English were identified by searching in PubMed from 2000 to 2013, with keywords "H. pylori". Important references from selected articles were also retrieved from Elsevier, Wiley, EBSCO, and SPRINGER. The Chinese articles published were searched from China National Knowledge Infrastructure (CNKI). Articles about "prevalence", "gastric carcinoma", "peptic ulcer", "gastroesophageal reflux disease", "functional dyspepsia", "pathogenic mechanism", "therapy", "eradication rate", "antibiotic resistance", and "gene polymorphisms" were selected. The decreased infection rates of H. pylori could also be linked to the changed disease spectrum, such as the decreased morbidity and recurrence rate of H. pylori-related peptic ulcer, and the increased morbidity of gastroesophageal reflux. Although different treatment regimens have been used for H. pylori infection, the H. pylori eradication rate declined gradually. Due to primary resistance to antibiotics, the gene polymorphism of host and infected strain, and the therapy regimes, H. pylori eradication became even more difficult. The prevalence of H. pylori infection had been decreasing, but the rate of eradication failure has dramatically risen in many countries due to resistance to antibiotic. H. pylori therapy in clinical practice is becoming progressively more difficult.
Sahin, Abdurrahman; Cihangiroglu, Gulcin; Bilgic, Yilmaz; Calhan, Turan; Cengiz, Mustafa
The primary reason for obtaining duodenal biopsy sample is to diagnose celiac disease. Helicobacter pylori (H. pylori) and drug injury are common causes of duodenitis. The aim of this retrospective study was to explore effects of H. pylori and drugs on duodenal mucosa. Duodenal biopsy samples of patients who underwent upper gastrointestinal endoscopy (UGIE) between February 2014 and December 2014 were retrospectively examined. Clinical symptoms, referral indications, endoscopic findings, H. pylori status, and drug history were recorded. Duodenal biopsy findings were compared based on presence of H. pylori and drug history. Of 2389 patients who underwent UGIE, 206 had duodenal biopsy. Eight patients (3.9%) were diagnosed with celiac disease. After excluding cases with celiac disease, 76 patients of remaining 198 patients (36.9%) had duodenal histopathological abnormality. H. pylori was found in 95 (47.9%) patients. Drug usage was less common (42%). Of patients who had histopathological duodenitis, 59% were H. pylori-infected. Rate of duodenitis was higher in H. pylori (+) group than in H. pylori (-) group (45% vs 27.1%; odds ratio, 2.4; 95% confidence interval, 1.3-4.4; p=0.005). There was no difference between groups regarding drug use in terms of histopathological duodenitis. H. pylori is the major contributor to duodenitis in high prevalence regions. Serological testing may be more appropriate before performing duodenal biopsy in patients with suspected celiac disease.
More than 50% of the world population is infected with Helicobacter pylori (H. pylori). The bacterium highly links to peptic ulcer diseases and duodenal ulcer, which was classified as a group I carcinogen in 1994 by the WHO. The pathogenesis of H. pylori is contributed by its virulence factors including urease, flagella, vacuolating cytotoxin A (VacA), cytotoxin-associated gene antigen (Cag A), and others. Of those virulence factors, VacA and CagA play the key roles. Infection with H. pylori vacA-positive strains can lead to vacuolation and apoptosis, whereas infection with cagA-positive strains might result in severe gastric inflammation and gastric cancer. Numerous medicinal plants have been reported for their anti-H. pylori activity, and the relevant active compounds including polyphenols, flavonoids, quinones, coumarins, terpenoids, and alkaloids have been studied. The anti-H. pylori action mechanisms, including inhibition of enzymatic (urease, DNA gyrase, dihydrofolate reductase, N-acetyltransferase, and myeloperoxidase) and adhesive activities, high redox potential, and hydrophilic/hydrophobic natures of compounds, have also been discussed in detail. H. pylori-induced gastric inflammation may progress to superficial gastritis, atrophic gastritis, and finally gastric cancer. Many natural products have anti-H. pylori-induced inflammation activity and the relevant mechanisms include suppression of nuclear factor-κB and mitogen-activated protein kinase pathway activation and inhibition of oxidative stress. Anti-H. pylori induced gastric inflammatory effects of plant products, including quercetin, apigenin, carotenoids-rich algae, tea product, garlic extract, apple peel polyphenol, and finger-root extract, have been documented. In conclusion, many medicinal plant products possess anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect. Those plant products have showed great potential as pharmaceutical candidates for H. pylori
Broide, Efrat; Richter, Vered; Mendlovic, Sonia; Shalem, Tzippora; Eindor-Abarbanel, Adi; Moss, Steven F; Shirin, Haim
Purpose The prevalence of Helicobacter pylori gastritis has been declining, whereas H. pylori-negative gastritis has become more common. We evaluated chronic gastritis in children with regard to H. pylori status and celiac disease (CD). Patients and methods Demographic, clinical, endoscopic, and histologic features of children who underwent elective esophagogastroduodenoscopy were reviewed retrospectively. Gastric biopsies from the antrum and corpus of the stomach were graded using the Updated Sydney System. H. pylori presence was defined by hematoxylin and eosin, Giemsa, or immunohistochemical staining and urease testing. Results A total of 184 children (61.9% female) met the study criteria with a mean age of 10 years. A total of 122 (66.3%) patients had chronic gastritis; 74 (60.7%) were H. pylori-negative. Children with H. pylori-negative gastritis were younger (p=0.003), were less likely to present with abdominal pain (p=0.02), and were mostly of non-Arabic origin (p=0.011). Nodular gastritis was found to be less prevalent in H. pylori-negative gastritis (6.8%) compared with H. pylori-positive gastritis (35.4%, p<0.001). The grade of mononuclear infiltrates and neutrophil density was more severe in the H. pylori-positive group (p<0.001). Pan-gastritis and lymphoid follicles were associated most commonly with H. pylori. Although less typical, lymphoid follicles were demonstrated in 51.3% of H. pylori-negative patients. The presence or absence of CD was not associated with histologic findings in H. pylori-negative gastritis. Conclusion Our findings suggest that lymphoid follicles are a feature of H. pylori-negative gastritis in children independent of their CD status. PMID:28860835
Tanaka, Shingo; Nagashima, Hiroyuki; Uotani, Takahiro; Graham, David Y; Yamaoka, Yoshio
In vitro studies have shown that Helicobacter pylori (H. pylori) infection induces autophagy in gastric epithelial cells. However, prolonged exposure to H. pylori reduces autophagy by preventing maturation of the autolysosome. The alterations of the autophagy-related genes in H. pylori infection are not yet fully understood. We analyzed autophagy-related gene expression in H. pylori-infected gastric mucosa compared with uninfected gastric mucosa obtained from 136 Bhutanese volunteers with mild dyspeptic symptoms. We also studied single nucleotide polymorphisms (SNPs) of autophagy-related gene in 283 Bhutanese participants to identify the influence on susceptibility to H. pylori infection. Microarray analysis of 226 autophagy-related genes showed that 16 genes were upregulated (7%) and nine were downregulated (4%). We used quantitative reverse transcriptase polymerase chain reaction to measure mRNA levels of the downregulated genes (ATG16L1, ATG5, ATG4D, and ATG9A) that were core molecules of autophagy. ATG16L1 and ATG5 mRNA levels in H. pylori-positive specimens (n=86) were significantly less than those in H. pylori-negative specimens (n=50). ATG16L1 mRNA levels were inversely related to H. pylori density. We also compared SNPs of ATG16L1 (rs2241880) among 206 H. pylori-positive and 77 H. pylori-negative subjects. The odds ratio for the presence of H. pylori in the GG genotype was 0.40 (95% CI: 0.18-0.91) relative to the AA/AG genotypes. Autophagy-related gene expression profiling using high-throughput microarray analysis indicated that downregulation of core autophagy machinery genes may depress autophagy functions and possibly provide a better intracellular habit for H. pylori in gastric epithelial cells. © 2017 John Wiley & Sons Ltd.
Broide, Efrat; Richter, Vered; Mendlovic, Sonia; Shalem, Tzippora; Eindor-Abarbanel, Adi; Moss, Steven F; Shirin, Haim
The prevalence of Helicobacter pylori gastritis has been declining, whereas H. pylori-negative gastritis has become more common. We evaluated chronic gastritis in children with regard to H. pylori status and celiac disease (CD). Demographic, clinical, endoscopic, and histologic features of children who underwent elective esophagogastroduodenoscopy were reviewed retrospectively. Gastric biopsies from the antrum and corpus of the stomach were graded using the Updated Sydney System. H. pylori presence was defined by hematoxylin and eosin, Giemsa, or immunohistochemical staining and urease testing. A total of 184 children (61.9% female) met the study criteria with a mean age of 10 years. A total of 122 (66.3%) patients had chronic gastritis; 74 (60.7%) were H. pylori-negative. Children with H. pylori-negative gastritis were younger (p=0.003), were less likely to present with abdominal pain (p=0.02), and were mostly of non-Arabic origin (p=0.011). Nodular gastritis was found to be less prevalent in H. pylori-negative gastritis (6.8%) compared with H. pylori-positive gastritis (35.4%, p<0.001). The grade of mononuclear infiltrates and neutrophil density was more severe in the H. pylori-positive group (p<0.001). Pan-gastritis and lymphoid follicles were associated most commonly with H. pylori. Although less typical, lymphoid follicles were demonstrated in 51.3% of H. pylori-negative patients. The presence or absence of CD was not associated with histologic findings in H. pylori-negative gastritis. Our findings suggest that lymphoid follicles are a feature of H. pylori-negative gastritis in children independent of their CD status.
Andreica, V; Suciu, A; Dumitraşcu, D; Drăghici, A; Pascu, O; Suciu, M; Ban, A
The biochemical changes induced in the gastric juice by the presence of Campylobacter pylori (CP) were followed up in 151 patients with various gastric and duodenal diseases. The diagnosis of CP infection was made by the urease test. In the presence of CP urea decreased in the gastric juice and ammonia increased. The sialic acid, fucose and hexoses, glucide components of the mucus glycoproteins dissolved in the gastric juice, underwent no change in the presence of CP. The hexosamines in the gastric mucus increased significantly in CP patients. Urease activity is present in the gastric juice even in the absence of CP, probably due to other microorganisms present in the human stomach. This does not exclude the use of the urease test for the diagnosis of CP infection. However the test can only be used in the bioptically removed gastric mucosa samples, not in the gastric juice.
Yang, Jyh-Chin; Yang, Hung-Chih; Shun, Chia-Tung; Wang, Teh-Hong; Chien, Chiang-Ting; Kao, John Y.
The inflammasome/caspase-1 signaling pathway in immune cells plays a critical role in bacterial pathogenesis; however, the regulation of this pathway in the gastric epithelium during Helicobacter pylori infection is yet to be elucidated. Here, we investigated the effect of catechins (CAs), sialic acid (SA), or combination of CA and SA (CASA) on H. pylori-induced caspase-1-mediated epithelial damage, as well as H. pylori colonization in vitro (AGS cells) and in vivo (BALB/c mice). Our results indicate that the activity of caspase-1 and the expression of its downstream substrate IL-1β were upregulated in H. pylori-infected AGS cells. In addition, we observed increased oxidative stress, NADPH oxidase gp91phox, CD68, caspase-1/IL-1β, and apoptosis, but decreased autophagy, in the gastric mucosa of H. pylori-infected mice. We have further demonstrated that treatment with CASA led to synergistic anti-H. pylori activity and was more effective than treatment with CA or SA alone. In particular, treatment with CASA for 10 days eradicated H. pylori infection in up to 95% of H. pylori-infected mice. Taken together, we suggest that the pathogenesis of H. pylori involves a gastric epithelial inflammasome/caspase-1 signaling pathway, and our results show that CASA was able to attenuate this pathway and effectively eradicate H. pylori infection. PMID:23653660
Lopes, Ana Isabel; Vale, Filipa F; Oleastro, Mónica
Considering the recommended indications for Helicobacter pylori (H. pylori) eradication therapy and the broad spectrum of available diagnostic methods, a reliable diagnosis is mandatory both before and after eradication therapy. Only highly accurate tests should be used in clinical practice, and the sensitivity and specificity of an adequate test should exceed 90%. The choice of tests should take into account clinical circumstances, the likelihood ratio of positive and negative tests, the cost-effectiveness of the testing strategy and the availability of the tests. This review concerns some of the most recent developments in diagnostic methods of H. pylori infection, namely the contribution of novel endoscopic evaluation methodologies for the diagnosis of H. pylori infection, such as magnifying endoscopy techniques and chromoendoscopy. In addition, the diagnostic contribution of histology and the urea breath test was explored recently in specific clinical settings and patient groups. Recent studies recommend enhancing the number of biopsy fragments for the rapid urease test. Bacterial culture from the gastric biopsy is the gold standard technique, and is recommended for antibiotic susceptibility test. Serology is used for initial screening and the stool antigen test is particularly used when the urea breath test is not available, while molecular methods have gained attention mostly for detecting antibiotic resistance. PMID:25071324
Whalen, Michael B; Massidda, Orietta
Helicobacter pylori is a Gram-negative ε-proteobacterium that colonizes about 50% of humans. Some pertinent characteristics are that it can survive the acid of the stomach, produces urease to neutralize it and is motile due to apical flagella. Not surprisingly given its wide distribution, it has long colonized mankind and its genome encodes many features that allows this. Consequently, it frequently has a persistent lifelong association with humans and, differently from most pathogens that are transmitted horizontally, it is preferentially transmitted vertically, often from mother to child. A variety of genes and polymorphisms, both in H pylori and in humans, mediate the complex host-bacterium relationship, and can also determine if and what pathologies will be triggered by the species. H. pylori is naturally transformable, very recombinogenic and has a high mutation rate. Microbiota studies of the stomach have shown it to be an important species with a potentially regulatory role for the gastric microbial community. Likewise, epidemiological work has suggested that, while it clearly increases the risk of peptic ulcers and gastric cancer in some populations, it is also associated with lower risk of esophageal cancer and several other important pathologies. More recently, antibacterial resistant strains have been isolated, posing a problem for public health officials who called for its eradication. Hence, study of H. pylori and how it interacts with us can help revealing mutualistic or pathogenic interactions and the immune response in the digestive niche.
Mattana, C M; Vega, A E; Flores, G; de Domeniconi, A G; de Centorbi, O N
It has been suggested that oral dissemination might be the major transmission vehicle for Helicobacter pylori, and that dental plaque might act as its reservoir. The presence of H. pylori was investigated in 62 odontological male and female patients (average age: 35 years old). Samples were taken from supragingival plaque, placed in 0.3 ml of thioglycolate broth, cultured within 12 h in Mueller-Hinton agar with the addition of 5-7% of sheep blood and antibiotic supplement, and incubated at 37 degrees C in microaerophilia for 5-7 days. Typical colonies were identified by gram, urease, oxidase and catalase. H. pylori was detected in a 15 year-old patient suffering from gastric acidity (1.61% positivity index). The medium used facilitated recovery of the agent from a sample abundant in germs. H. pylori was not recovered from the same patient 12 months later, suggesting that there might have been a transitory passage by gastric reflux or that the bacterium was acquired from an exogenous source.
Lopes, Ana Isabel; Vale, Filipa F; Oleastro, Mónica
Considering the recommended indications for Helicobacter pylori (H. pylori) eradication therapy and the broad spectrum of available diagnostic methods, a reliable diagnosis is mandatory both before and after eradication therapy. Only highly accurate tests should be used in clinical practice, and the sensitivity and specificity of an adequate test should exceed 90%. The choice of tests should take into account clinical circumstances, the likelihood ratio of positive and negative tests, the cost-effectiveness of the testing strategy and the availability of the tests. This review concerns some of the most recent developments in diagnostic methods of H. pylori infection, namely the contribution of novel endoscopic evaluation methodologies for the diagnosis of H. pylori infection, such as magnifying endoscopy techniques and chromoendoscopy. In addition, the diagnostic contribution of histology and the urea breath test was explored recently in specific clinical settings and patient groups. Recent studies recommend enhancing the number of biopsy fragments for the rapid urease test. Bacterial culture from the gastric biopsy is the gold standard technique, and is recommended for antibiotic susceptibility test. Serology is used for initial screening and the stool antigen test is particularly used when the urea breath test is not available, while molecular methods have gained attention mostly for detecting antibiotic resistance.
Isaeva, G Sh; Efimova, N G
The study involved 160 patients with chronic cholecystitis associated with chronic gastroduodenitis. Obtaining biopsy specimens of gastric mucosa and bile samples allowed to compare the microbial picture and the morphological structure of gastric mucosa in the same patient, to identify patterns of colonization of the stomach, 12 duodenal ulcer and gall bladder various microorganisms. At cytological examination was detected in the gall bladder G. lamblia in 47.5 +/- 3.95% of cases in the stomach--in 29.09 +/- 6.12% of cases. The frequency of H. pylori detection in biopsy of gastric mucosa amounted to 98.18 +/- 1.8% of cases, in 12-duodenum--93.75 +/- 1.9%, in the gall bladder--to 54.38 +/- 3.94%, in the bile duct--in 54.38 +/- 3.94%. It was found strict association between the detection of H. pylori and G. lamblia in the stomach--100% of H. pylori-infection combined with giardiasis. Morphological changes of gastric mucosa in the form of lymphoid infiltration detected mainly in the mixed-infection H. pylori and G. lamblia.
Pilotto, Alberto; Franceschi, Marilisa
Since the discovery of Helicobacter pylori (H. pylori) infection as the major cause of gastroduodenal disorders three decades ago, H. pylori has been the focus of active research and debate in the scientific community. Its linkage to several diseases, such as peptic ulcer disease, gastritis and gastric malignancy is incontestable. In particular, it has been noticed that, as the aged population is increasing worldwide, older people are at increased risk of developing several gastroduodenal diseases and related complications. At the same time, gastric cancer is definitely more frequent in elderly than in adult and young people. In addition, it has been showed that peptic ulcer and related complications occur much more commonly in aged individuals than in young people, resulting in a significantly higher mortality. Although this infection plays a crucial role in gastrointestinal disorders affecting all age groups and in particular older people, only a few studies have been published regarding the latter. This article presents an overview of the epidemiology, diagnosis, clinical manifestations and therapy of H. pylori infection in elderly people. PMID:24914358
Windsor, H M; O'Rourke, J
As the scientific community approaches the twentieth anniversary of the first isolation of H. pylori, it appears that despite the wealth of articles published in journals throughout the world every month, there are still many unanswered questions about the microbiology of this bacterium and others in the genus Helicobacter.
Tanaka, Jiro; Suzuki, Toshihiko; Mimuro, Hitomi; Sasakawa, Chihiro
Genetic and functional studies have indicated that the type IV secretion system (TFSS) of Helicobacter pylori forms a secretion complex in the cell envelope that protrudes towards the outside in order to inject CagA protein into gastric epithelial cells. However, the proposed structural model is based on partial amino acid homology with the components of the Agrobacterium tumefaciens TFSS. Therefore, we undertook the identification of the structural features of the TFSS exposed on the surface of H. pylori and found that filamentous structures present on the bacterial surface are related to the secretion apparatus. Using immunofluorescence microscopy with antibodies directed to tyrosine-phosphorylated CagA (pY-CagA) and Hp0532 (VirB7) in the infection assay, pY-CagA signals were detected just below the host cell-attached bacteria, where Hp0532 (VirB7) signals were detected as co-localized, suggesting that the CagA injected into the host cell through the TFSS apparatus is still mostly confined to the areas just below the attached bacteria after being phosphorylated. Furthermore, the filamentous structures on bacterium were found to be associated with Hp0532 (VirB7) or Hp0528 (VirB9), the major components of TFSS, by immunogold electron microscopy. These results strongly suggest that the H. pylori TFSS apparatus is a filamentous macromolecular structure protruding from the bacterial envelope.
Wong, Frank; Rayner-Hartley, Erin; Byrne, Michael F
Helicobacter pylori (H. pylori) infection has been clearly linked to peptic ulcer disease and some gastrointestinal malignancies. Increasing evidence demonstrates possible associations to disease states in other organ systems, known as the extraintestinal manifestations of H. pylori. Different conditions associated with H. pylori infection include those from hematologic, cardiopulmonary, metabolic, neurologic, and dermatologic systems. The aim of this article is to provide a concise review of the evidence that supports or refutes the associations of H. pylori and its proposed extraintestinal manifestations. Based on data from the literature, PUD, mucosal associated lymphoid tumors lymphoma, and gastric adenocarcinoma has well-established links. Current evidence most supports extraintestinal manifestations with H. pylori in immune thrombocytopenic purpura, iron deficiency anemia, urticaria, Parkinson’s, migraines and rosacea; however, there is still plausible link with other diseases that requires further research. PMID:25232230
Zhu, Xinyan; Liu, Fei
Over 80% population with Helicobacter pylori (H. pylori) infection is asymptomatic. H. pylori was considered as a primary reason for various natural gastric physiopathology. Increased antibiotic resistance and less medication compliance lead to the failure of antibiotic eradication therapy. Probiotics have been applied as a supplementary treatment in H. pylori eradication therapy in recent years. They have direct and indirect inhibitory effects on H. pylori in both animal models and clinical trials. Because of the improvement in eradication rates and therapy-related side effects, probiotics have been considered as the useful supplementation to current eradication therapy although the treatment outcomes were controversial due to the heterogeneity of probiotics in species, strains, doses and therapeutic duration. Despite the positive role of probiotics, several factors need to be further considered during the application of probiotics. At last, the adverse effects of probiotics are notable. Further investigation into the safety of adjuvant probiotics to present H. pylori eradication therapy is still needed.
Hagymási, Krisztina; Tulassay, Zsolt
Helicobacter pylori (H. pylori) infects more than half of the world’s human population, but only 1% to 3% of infected people consequently develop gastric adenocarcinomas. The clinical outcome of the infection is determined by host genetic predisposition, bacterial virulence factors, and environmental factors. The association between H. pylori infection and chronic active gastritis, peptic ulcer disease, gastric cell carcinoma, and B cell mucosa-associated lymphoid tissue lymphoma has been well established. With the exception of unexplained iron deficiency anemia and idiopathic thrombocytopenic purpura, H. pylori infection has no proven role in extraintestinal diseases. On the other hand, there is data showing that H. pylori infection could be beneficial for some human diseases. The unpredictability of the long-term consequences of H. pylori infection and the economic challenge in eradicating it is why identification of high-risk individuals is crucial. PMID:24914360
Immunology Helicobacter pylori is a Gram negative, microaerophilic, spiral shaped bacterium that is the causative agent of a variety of gastric...H. pylori is a small, Gram negative, spiral shaped, microaerobe that has multiple (four to six) polar, sheathed flagellae that are responsible...the specified gene. A. β-lactams prevent the completion of the peptidoglycan layer of H. pylori through their interaction with penicillin binding
Choi, Yun Mi; Kim, Tae Yong; Kim, Eui Young; Jang, Eun Kyung; Jeon, Min Ji; Kim, Won Gu; Shong, Young Kee; Kim, Won Bae
Background/Aims There have been controversial reports linking Helicobacter pylori infection to autoimmune thyroid disease (AITD). However, data regarding the relationship are limited for Asian populations, which have an extremely high prevalence of H. pylori infection. We performed this study to investigate the association between H. pylori infection and AITD in Koreans. Methods This study involved adults aged 30 to 70 years who had visited a health promotion center. A total of 5,502 subjects were analysed. Thyroid status was assessed by free thyroxine, thyroid stimulating hormone, and anti-thyroid peroxidase antibody (TPO-Ab). Immunoglobulin G (IgG) antibodies to H. pylori were measured as an indication of H. pylori infection. We compared the prevalence of TPO-Ab in subjects with and without H. pylori infection. Results H. pylori IgG antibodies were found in 2,875 subjects (52.3%), and TPO-Ab were found in 430 (7.8%). Individuals positive for H. pylori Ab were older than those negative for H. pylori Ab (p < 0.01). The proportion of females was significantly higher in the TPO-Ab positive group (41.0% vs. 64.2%, p < 0.01). Prevalence of TPO-Ab positivity was higher in subjects with H. pylori infection (8.6% vs. 7.00%, p = 0.03), and this association was significant after adjusting for age, sex, and body mass index (odds ratio, 1.02; 95% confidence interval, 1.00 to 1.03; p = 0.04). Conclusions In our study, prevalence of TPO-Ab positivity is more frequent in subjects with H. pylori infection. Our findings suggest H. pylori infection may play a role in the development of autoimmune thyroiditis. PMID:28092700
Choi, Yun Mi; Kim, Tae Yong; Kim, Eui Young; Jang, Eun Kyung; Jeon, Min Ji; Kim, Won Gu; Shong, Young Kee; Kim, Won Bae
There have been controversial reports linking Helicobacter pylori infection to autoimmune thyroid disease (AITD). However, data regarding the relationship are limited for Asian populations, which have an extremely high prevalence of H. pylori infection. We performed this study to investigate the association between H. pylori infection and AITD in Koreans. This study involved adults aged 30 to 70 years who had visited a health promotion center. A total of 5,502 subjects were analysed. Thyroid status was assessed by free thyroxine, thyroid stimulating hormone, and anti-thyroid peroxidase antibody (TPO-Ab). Immunoglobulin G (IgG) antibodies to H. pylori were measured as an indication of H. pylori infection. We compared the prevalence of TPO-Ab in subjects with and without H. pylori infection. H. pylori IgG antibodies were found in 2,875 subjects (52.3%), and TPO-Ab were found in 430 (7.8%). Individuals positive for H. pylori Ab were older than those negative for H. pylori Ab (p < 0.01). The proportion of females was significantly higher in the TPO-Ab positive group (41.0% vs. 64.2%, p < 0.01). Prevalence of TPO-Ab positivity was higher in subjects with H. pylori infection (8.6% vs. 7.00%, p = 0.03), and this association was significant after adjusting for age, sex, and body mass index (odds ratio, 1.02; 95% confidence interval, 1.00 to 1.03; p = 0.04). In our study, prevalence of TPO-Ab positivity is more frequent in subjects with H. pylori infection. Our findings suggest H. pylori infection may play a role in the development of autoimmune thyroiditis.
Fedichkina, T P; Solenova, L G; Zykova, I E
There are considered the issues related to the possibility to rate of Helicobacter pylori (H. pylori) content in drinking water. There is described the mechanism of of biofilm formation. The description refers to the biofilm formation mechanism in water supply systems and the existence of H. pylori in those systems. The objective premises of the definition of H. pylori as a potential limiting factor for assessing the quality of drinking water have been validated as follows: H. pylori is an etiologic factor associated to the development of chronic antral gastritis, gastric ulcer and duodenal ulcer, and gastric cancer either, in the Russian population the rate of infection with H. pylori falls within range of 56 - 90%, water supply pathway now can be considered as a source of infection of the population with H. pylori, the existence of WHO regulatory documents considering H. pylori as a candidate for standardization of the quality of the drinking water quite common occurrence of biocorrosion, the reduction of sanitary water network reliability, that creates the possibility of concentrating H. pylori in some areas of the water system and its delivery to the consumer of drinking water, and causes the necessity of the prevention of H. pylori-associated gastric pathology of the population. A comprehensive and harmonized approach to H. pylori is required to consider it as a candidate to its rating in drinking water. Bearing in mind the large economic losses due to, on the one hand, the prevalence of disease caused by H. pylori, and, on the other hand, the biocorrosion of water supply system, the problem is both relevant in terms of communal hygiene and economy.
Frick-Cheng, Arwen E.; Pyburn, Tasia M.; Voss, Bradley J.; McDonald, W. Hayes
ABSTRACT Bacterial type IV secretion systems (T4SSs) can function to export or import DNA, and can deliver effector proteins into a wide range of target cells. Relatively little is known about the structural organization of T4SSs that secrete effector proteins. In this report, we describe the isolation and analysis of a membrane-spanning core complex from the Helicobacter pylori cag T4SS, which has an important role in the pathogenesis of gastric cancer. We show that this complex contains five H. pylori proteins, CagM, CagT, Cag3, CagX, and CagY, each of which is required for cag T4SS activity. CagX and CagY are orthologous to the VirB9 and VirB10 components of T4SSs in other bacterial species, and the other three Cag proteins are unique to H. pylori. Negative stain single-particle electron microscopy revealed complexes 41 nm in diameter, characterized by a 19-nm-diameter central ring linked to an outer ring by spoke-like linkers. Incomplete complexes formed by Δcag3 or ΔcagT mutants retain the 19-nm-diameter ring but lack an organized outer ring. Immunogold labeling studies confirm that Cag3 is a peripheral component of the complex. The cag T4SS core complex has an overall diameter and structural organization that differ considerably from the corresponding features of conjugative T4SSs. These results highlight specialized features of the H. pylori cag T4SS that are optimized for function in the human gastric mucosal environment. PMID:26758182
Epstein, Aaron; Wing, Deborah A; Ouzounian, Joseph G; Miller, David A; Lee, Richard H
An association between Helicobacter pylori (H. pylori) and thrombocytopenia has been demonstrated in the literature in a non-pregnant population. The purpose of this study was to determine whether or not there is a similar association in the third trimester of pregnancy in a Hispanic population. This is a secondary analysis of 82 pregnant Hispanic women with and without hyperemesis gravidarum who underwent serologic evaluation for H. pylori IgG. Results of complete blood counts obtained in the third trimester were analysed for thrombocytopenia. Of the 82 subjects who had H. pylori testing, 54 subjects had both serum H. pylori IgG results and third trimester platelet levels. The prevalence of thrombocytopenia was 11.1% (6/54). Thirty-six subjects were seropositive for H. pylori IgG and 18 subjects were seronegative. Of the 36 subjects who were H. pylori seropositive, four (11.1%) developed thrombocytopenia compared to three of 18 (16.7%) H. pylori seronegative subjects (P = 0.67). There was no difference between the groups in their mean platelet values (205 K/cu mm vs. 212 K/cu mm, P = 0.69). In this limited study, we found no association between H. pylori and thrombocytopenia in the pregnant Hispanic population.
Horvath, Bela; Pai, Rish K
Hyperplastic polyps of the stomach are routinely encountered during upper endoscopy and often arise in the setting of abnormal surrounding mucosa, particularly Helicobacter pylori, autoimmune gastritis, and reactive gastropathy. Not infrequently gastroenterologists fail to biopsy the surrounding mucosa, thus determining the underlying etiology of the gastric hyperplastic polyp can be difficult. Recently, the Rodger C. Haggitt Gastrointestinal Pathology Society published guidelines on the use of special stains. The society guidelines indicate that H pylori are not usually present in hyperplastic polyps and special stains in this setting may have limited utility. We analyzed the histologic features of 32 gastric hyperplastic polyps in which the nonpolypoid mucosa demonstrated H pylori gastritis. A consecutive series of 50 hyperplastic polyps in which no surrounding mucosa was sampled was also analyzed. When H pylori are identified in biopsies of the nonpolypoid mucosa, it is also commonly present within the polyp tissue (22/32, 69%). The majority of H pylori organisms were identified on routine hematoxylin and eosin stain (16/22, 72%). In contrast, H pylori were only seen in 2/50 consecutive hyperplastic polyps in which the surrounding mucosa was not sampled. Compared with the hyperplastic polyps that lack the organisms, H pylori associated hyperplastic polyps more commonly had dense lymphoplasmacytic inflammation (P = .0001) and neutrophils within gastric epithelium (P = .036). Polyp location, number, size, and presence of intestinal metaplasia was not associated with H pylori These results provide empirical data to guide evaluation of hyperplastic polyps for H pylori.
Kalisperati, Polyxeni; Spanou, Evangelia; Pateras, Ioannis S.; Korkolopoulou, Penelope; Varvarigou, Anastasia; Karavokyros, Ioannis; Gorgoulis, Vassilis G.; Vlachoyiannopoulos, Panayiotis G.; Sougioultzis, Stavros
Helicobacter pylori (H. pylori) is a Gram negative bacterium that colonizes the stomach of almost half human population. It has evolved to escape immune surveillance, establishes lifelong inflammation, predisposing to genomic instability and DNA damage, notably double strand breaks. The epithelial host cell responds by activation of DNA damage repair (DDR) machinery that seems to be compromised by the infection. It is therefore now accepted that genetic damage is a major mechanism operating in cases of H. pylori induced carcinogenesis. Here, we review the data on the molecular pathways involved in DNA damage and DDR activation during H. pylori infection. PMID:28289428
Sood, M; Joshi, S; Akobeng, A; Mitchell, J; Thomas, A
Aims: To compare the height, weight, and body mass index (BMI) of children presenting with dyspeptic symptoms and Helicobacter pylori infection, to those with dyspepsia but without the infection. Methods: A retrospective chart review of 257 children was performed. 13C urea breath test was performed to detect H pylori infection; weight and height were recorded and BMI was calculated. Weight, height, and BMI SD scores were determined using the 1990 UK normative data. The Index of Multiple Deprivation 2004 (IMD 2004) scores, which measure deprivation at small area level, were calculated from the patients' postcodes. Results: Ninety seven of the 257 children were H pylori positive. The mean age at diagnosis and presenting symptoms of H pylori positive and negative patients were similar. The mean IMD 2004 scores for children with H pylori infection were significantly higher compared to H pylori negative patients, suggesting that children with the infection came from relatively more deprived areas. The mean weight and height SD score were significantly lower for children with H pylori infection compared to those without. However, this difference was no longer significant after adjusting for socioeconomic deprivation and ethnic differences between the groups. Conclusion: Children with dyspepsia and H pylori infection were shorter and lighter than patients with similar symptoms but no infection. The differences in anthropometry may be due to socioeconomic and ethnic factors rather than H pylori infection. PMID:15956048
Fatema, J; Khan, A H; Uddin, M J; Rahman, M H; Saha, M; Safwath, S A; Alam, M J; Mamun, M A
This cross sectional study was designed to see association of chronic gastritis including its type with H. pylori infection. Consecutive patients undergoing endoscopic examination having histopathological evidence of chronic gastritis were enrolled in the study and was done in Sylhet MAG Osmani Medical College from July 2011 to June 2012. Biopsies were taken from antrum, body and fundus in all patients. Histopathological examinations were done using H-E stain and for detection of H. pylori, rapid urease test, anti-H.pylori antibody test and histopathological test with modified Giemsa stain were done. Patients having results positive in at least two methods were considered infected by H. pylori. Total 80 dyspeptic patients having chronic gastritis were evaluated. Out of them 67(83.8%) had H. pylori infection and 13(16.2%) were H. pylori negative. Among all patients 57(71.2%) had pangastritis and 23(28.8%) had antral gastritis with female and male predominance respectively. H. pylori infection was present in 49(86.0%) cases of pangastritis and 18(78.3%) cases of antral gastritis. H. pylori infection was a little higher among males (34, 50.7%) females (33, 49.3%). H. pylori infection is the predominant cause of chronic gastritis and pangastritis is the major type.
Shao, Yun; Sun, Kun; Xu, Wei; Li, Xiao-Lin; Shen, Hong; Sun, Wei-Hao
Gastric cancer is one of the most frequent neoplasms and a main cause of death worldwide, especially in China and Japan. Numerous epidemiological, animal and experimental studies support a positive association between chronic Helicobacter pylori (H. pylori) infection and the development of gastric cancer. However, the exact mechanism whereby H. pylori causes gastric carcinogenesis remains unclear. It has been demonstrated that expression of cyclooxygenase-2 (COX-2) is elevated in gastric carcinomas and in their precursor lesions. In this review, we present the latest clinical and experimental evidence showing the role of gastrin and COX-2 in H. pylori-infected patients and their possible association with gastric cancer risk.
Goodman, Karen J; Jacobson, Kevan; van Zanten, Sander Veldhuyzen
In 2006, the Canadian Helicobacter Study Group identified Aboriginal communities among Canadian population groups most at risk of Helicobacter pylori-associated disease. The objective of this systematic review was to summarize what is known about the H pylori-associated disease burden in Canadian and related Arctic Aboriginal populations to identify gaps in knowledge. Six health literature databases were systematically searched to identify reports on H pylori prevalence in Canadian population groups, or any topic related to H pylori in Canadian Aboriginals, Alaska Natives or Aboriginals of other Arctic regions. Identified reports were organized by subtopic and summarized in narrative form. Key data from studies of H pylori prevalence in defined populations were summarized in tabular form. A few Arctic Aboriginal communities were represented in the literature: two Canadian Inuit; one Canadian First Nation; two Greenland Inuit; one Russian Chutkotka Native; and several Alaska Native studies. These studies uniformly showed elevated H pylori prevalence; a few studies also showed elevated occurrence of H pylori-related diseases and high rates of treatment failure. Based on the evidence, it would be warranted for clinicians to relax the criteria for investigating H pylori and related diseases in patients from Arctic Aboriginal communities, and to pursue post-therapy confirmation of eradication. Additional community-based research is needed to develop public health policies for reducing H pylori-associated health risks in such communities. PMID:18354758
Lin, Yang-Sheng; Chen, Ming-Jen; Shih, Shou-Chuan; Bair, Ming-Joug; Fang, Ching-Ju; Wang, Horng-Yuan
The Maastricht IV/Florence Consensus Report and the Second Asia-Pacific Consensus Guidelines strongly recommend eradication of Helicobacter pylori (H. pylori) in patients with previous gastric neoplasia who have undergone gastric surgery. However, the guidelines do not mention optimal timing, eradication regimens, diagnostic tools, and follow-up strategies for patients undergoing gastrectomy and do not indicate if eradication of H. pylori reduces the risk of marginal ulcer or stump cancer in the residual stomach after gastrectomy. The purpose of this review is to provide an update which may help physicians to properly manage H. pylori infection in patients who have undergone gastric surgery. This review focuses on (1) the microenvironment change in the stomach after gastrectomy; (2) the phenomenon of spontaneous clearance of H. pylori after gastrectomy; (3) the effects of H. pylori on gastric atrophy and intestinal metaplasia after gastrectomy; (4) incidence and clinical features of ulcers developing after gastrectomy; (5) does eradication of H. pylori reduce the risk of gastric stump cancer in the residual stomach? (6) does eradication of H. pylori reduce the risk of secondary metachronous gastric cancer in the residual stomach? and (7) optimal timing and regimens for H. pylori eradication, diagnostic tools and follow-up strategies for patients undergoing gastrectomy. PMID:24833857
Mirzaee, Vahid; Molaei, Mahsa; Shalmani, Hamid Mohaghegh; Zali, Mohammad Reza
AIM: To determine the expression of DNA (MMR) proteins, including hMLH1 and hMSH2, in gastric epithelial cells in the patients with or without Helicobacter pylori (H pylori)-infected gastritis. METHODS: Fifty H pylori-positive patients and 50 H pylori-negative patients were enrolled in the study. During endoscopy of patients with non-ulcer dyspepsia, two antral and two corpus biopsies were taken for histological examination (Giemsa stain) and for immunohistochemical staining of hMLH1 and hMSH2. RESULTS: The percentage of epithelial cell nuclei that demonstrated positivity for hMLH1 staining was 84.14 ± 7.32% in H pylori-negative patients, while it was 73.34 ± 10.10% in H pylori-positive patients (P < 0.0001). No significant difference was seen between the two groups regarding the percentage of epithelial cell nuclei that demonstrated positivity for hMSH2 staining (81.16 ± 8.32% in H pylori-negative versus 78.24 ± 8.71% in H pylori-positive patients; P = 0.09). CONCLUSION: This study indicates that H pylori might promote development of gastric carcinoma at least in part through its ability to affect the DNA MMR system. PMID:19034977
al-Assi, M T; Genta, R M; Karttunen, T J; Graham, D Y
More convenient therapies are needed to treat Helicobacter pylori infection successfully. Clarithromycin and amoxycillin are effective against H. pylori both in vivo and in vitro. Recent success with a high dose amoxycillin-metronidazole combination therapy led us to evaluate clarithromycin-amoxycillin dual therapy for H. pylori infection. We tested the combination of clarithromycin 500 mg t.d.s. with meals plus amoxycillin 750 mg t.d.s. with meals for 10 days for its effect on H. pylori infection in 29 patients with documented H. pylori peptic ulcers. There were 27 men and 2 women, ranging in age from 23 to 77 years. H. pylori and ulcer status were evaluated at entry and at least 4 weeks after ending antimicrobial therapy. For ulcer healing, ranitidine 300 mg was given each evening for 6 weeks. H. pylori status was determined by CLOtest and histology. H. pylori infection was cured in 86% (95% CI = 78-99%). Compliance averaged 93% by pill count. Ten patients (34%) experienced mild side effects: eight reported dysgeusia and two had mild diarrhoea; none discontinued therapy because of side effects. We conclude that dual therapy with clarithromycin and amoxycillin is a safe and effective alternative regimen for the successful treatment of H. pylori infections.
Clayton, C L; Kleanthous, H; Coates, P J; Morgan, D D; Tabaqchali, S
A polymerase chain reaction (PCR) for the specific detection of Helicobacter pylori was developed with a single primer pair derived from the nucleotide sequence of the urease A gene of H. pylori. We achieved specific amplification of a 411-bp DNA fragment in H. pylori. After 35 cycles of amplification, the product could be detected by agarose gel electrophoresis and contained conserved single HinfI and AluI restriction sites. This fragment was amplified in all 50 strains of H. pylori tested, but it was not detected in other bacterial species, showing the PCR assay to be 100% specific. PCR DNA amplification was able to detect as few as 10 H. pylori cells. PCR detected H. pylori in 15 of 23 clinical human gastric biopsy samples, whereas culturing and microscopy detected H. pylori in only 7 of the samples found to be positive by PCR. Additional primer pairs based on the urease genes enabled the detection of H. pylori in paraffin-embedded human gastric biopsy samples. The detection of H. pylori by PCR will enable both retrospective and prospective analyses of clinical samples, elucidating the role of this organism in gastroduodenal disease. Images PMID:1734052
Park, Sanghoon; Chun, Hoon Jai
Gastric remnants are an inevitable consequence of partial gastrectomy following resection for gastric cancer. The presence of gastric stumps is itself a risk factor for redevelopment of gastric cancer. Helicobacter pylori (H. pylori) infection is also a well-known characteristic of gastric carcinogenesis. H. pylori colonization in the remnant stomach therefore draws special interest from clinicians in terms of stomach cancer development and pathogenesis; however, the H. pylori-infected gastric remnant is quite different from the intact organ in several aspects and researchers have expressed conflicting opinions with respect to its role in pathogenesis. For instance, H. pylori infection of the gastric stump produced controversial results in several recent studies. The prevalence of H. pylori infection in the gastric stump has varied among recent reports. Gastritis developing in the remnant stomach presents with a unique pattern of inflammation that is different from the pattern seen in ordinary gastritis of the intact organ. Bile refluxate also has a significant influence on the colonization of the stomach stump, with several studies reporting mixed results as well. In contrast, the elimination of H. pylori from the gastric stump has shown a dramatic impact on eradication rate. H. pylori elimination is recognized to be important for cancer prevention and considerable agreement of opinion is seen among researchers. To overcome the current discrepancies in the literature regarding the role of H. pylori in the gastric stump, further research is required. PMID:24659869
Mamori, Satoshi; Higashida, Akihiro; Kawara, Fumiaki; Ohnishi, Katsuhiro; Takeda, Akihiko; Senda, Eri; Ashida, Cho; Yamada, Hajime
AIM: To determine the general risk factors affecting the failure rate of first-line eradication therapy in Japanese patients with Helicobacter pylori (H. pylori) infection. METHODS: The present study enrolled 253 patients who had an H. pylori infection, underwent gastro-endoscopy, and were treated with H. pylori eradication therapy. Eradication therapy consisted of 30 mg lansoprazole plus 750 mg amoxicillin and 400 mg clarithromycin twice daily for 7 d. All of the patients underwent a 13C urea breath test at least 1 mo after the completion of eradication therapy. The current study investigated the independent factors associated with successful H. pylori eradication using a multiple logistic regression analysis. RESULTS: The overall success rate in the patients was 85.8%. Among the general factors examined in the multivariate analyses, only having an age less than 50 years was found to be significantly associated with a poor response to H. pylori eradication. Moreover, side effects were the only clinical factors in the patients who were under 50 years of age that significantly influenced the poor response to H. pylori eradication. CONCLUSION: H. pylori-positive elderly patients should undergo eradication therapy. In addition, it is necessary to improve H. pylori eradication therapy in younger patients. PMID:20806435
Cheung, Justin; Goodman, Karen; Munday, Rachel; Heavner, Karen; Huntington, Janis; Morse, John; Veldhuyzen van Zanten, Sander; Fedorak, Richard N; Corriveau, Andre; Bailey, Robert J
The Canadian North Helicobacter pylori (CANHelp) working group is a team composed of investigators, health officials and community leaders from Alberta and the Northwest Territories. The group's initial goals are to investigate the impact of H pylori infection on Canada's Arctic communities; subsequent goals include identifying treatment strategies that are effective in this region and developing recommendations for health policy aimed at management of H pylori infection. The team's investigations have begun with the Aklavik H pylori Project in the Aboriginal community of Aklavik, Northwest Territories.
Savoldi, E; Marinone, M G; Negrini, R; Facchinetti, D; Lanzini, A; Sapelli, P L
Attempts to detect Helicobacter pylori in dental plaque have given contrasting results, and the possibility of an oral-oral transmission of the infection remains unclear. In this study, a sensitive and specific immunoperoxidase method has been employed to assess the presence of H. pylori in dental plaque. Dental plaque smears from 80 patients undergoing gastroscopy were analyzed by an indirect immunoperoxidase test, employing a mixture of two monoclonal antibodies against H. pylori. No immunostained bacteria were shown in any of the examined dental plaque samples. H. pylori is not usually present in dental plaque, indicating that oral-oral transmission of the infection could be due to intermittent esophageal reflux only.
Velin, Dominique; Straubinger, Kathrin; Gerhard, Markus
The tight control of the innate and adaptive immune responses in the stomach mucosa during chronic Helicobacter pylori infection is of prime importance for the bacteria to persist and for the host to prevent inflammation-driven diseases. This review summarizes recent data on the roles of innate and adaptive immune responses during H. pylori/host interactions. In addition, the latest preclinical developments of H. pylori vaccines are discussed with a special focus on the clinical trial reported by Zeng et al., who provided evidence that oral vaccination significantly reduces the acquisition of natural H. pylori infection in children.
Goodman, K J; Jacobson, K; Veldhuyzen van Zanten, S
In 2006, the Canadian Helicobacter Study Group identified Aboriginal communities among Canadian population groups most at risk of Helicobacter pylori-associated disease. The objective of this systematic review was to summarize what is known about the H pylori-associated disease burden in Canadian and related Arctic Aboriginal populations to identify gaps in knowledge. Six health literature databases were systematically searched to identify reports on H pylori prevalence in Canadian population groups, or any topic related to H pylori in Canadian Aboriginals, Alaska Natives or Aboriginals of other Arctic regions. Identified reports were organized by subtopic and summarized in narrative form. Key data from studies of H pylori prevalence in defined populations were summarized in tabular form. A few Arctic Aboriginal communities were represented in the literature: two Canadian Inuit; one Canadian First Nation; two Greenland Inuit; one Russian Chutkotka Native; and several Alaska Native studies. These studies uniformly showed elevated H pylori prevalence; a few studies also showed elevated occurrence of H pylori-related diseases and high rates of treatment failure. Based on the evidence, it would be warranted for clinicians to relax the criteria for investigating H pylori and related diseases in patients from Arctic Aboriginal communities, and to pursue post-therapy confirmation of eradication. Additional community-based research is needed to develop public health policies for reducing H pylori-associated health risks in such communities.
Tsang, Jennifer; Smith, Todd G.; Pereira, Lara E.
Flagellar biogenesis in the gastric pathogen Helicobacter pylori involves a transcriptional hierarchy that utilizes all three sigma factors found in this bacterium (RpoD, RpoN and FliA). Transcription of the RpoN-dependent genes requires the sensor kinase FlgS and response regulator FlgR. It is thought that FlgS senses some cellular cue to regulate transcription of the RpoN-dependent flagellar genes, but this signal has yet to be identified. Previous studies showed that transcription of the RpoN-dependent genes is inhibited by mutations in flhA, which encodes a membrane-bound component of the flagellar protein export apparatus. We found that depending on the H. pylori strain used, insertion mutations in flhA had different effects on expression of RpoN-dependent genes. Mutations in flhA in H. pylori strains B128 and ATCC 43504 (the type strain) were generated by inserting a chloramphenicol resistance cassette so as to effectively eliminate expression of the gene (ΔflhA), or within the gene following codon 77 (designated flhA77) or codon 454 (designated flhA454), which could allow expression of truncated FlhA proteins. All three flhA mutations severely inhibited transcription of the RpoN-dependent genes flaB and flgE in H. pylori B128. In contrast, levels of flaB and flgE transcripts in H. pylori ATCC 43504 bearing either flhA77 or flhA454, but not ΔflhA, were ~60 % of wild-type levels. The FlhA454 variant was detected in membrane fractions prepared from H. pylori ATCC 43504 but not H. pylori B128, which may account for the phenotypic differences in the flhA mutations of the two strains. Taken together, these findings suggest that only the N-terminal region of FlhA is needed for transcription of the RpoN regulon. Interestingly, expression of an flaB′-′xylE reporter gene in H. pylori ATCC 43504 bearing the flhA77 allele was about eightfold higher than that of a strain with the wild-type allele, suggesting that expression of flaB is not only regulated at the
Ladas, S D; Katsogridakis, J; Malamou, H; Giannopoulou, H; Kesse-Elia, M; Raptis, S A
Helicobacter pylori and duodenogastric reflux are both recognised as playing aetiological roles in chronic gastritis. This study investigated whether H pylori colonisation of the antral mucosa and duodenogastric reflux are independent phenomena or have a causal relationship. Thirty eight patients (15 men, 23 women) aged (mean (SD)) 48 (17) years participated. Each patient underwent gastroscopy. Antral biopsy specimens were taken to investigate H pylori colonisation. In addition BrIDA-99mTc/111In-DTPA scintigraphy was used to quantify duodenogastric reflux. H pylori positive patients who were found to have duodenogastric reflux were treated with amoxycillin (1 g/d) and metronidazole (1.5 g/d) for seven days and four tablets of bismuth subcitrate daily for four weeks. Follow up antral biopsies and scintigraphy were repeated at six months. Duodenogastric reflux could not be found in 18 patients, including eight (44%) who were H pylori positive. Ten of the 11 patients who had duodenogastric reflux (reflux % 11.6 (9.2)), however, were H pylori positive (chi 2 = 6.26, p = 0.01). These 10 patients were given eradication treatment. At six months, in six patients who became H pylori negative, duodenogastric reflux was significantly reduced from a pretreatment value of 14.3% to 3.3% (two tail, paired t = 2.57, p = 0.016). These data suggest that H pylori may induced duodenogastric reflux which may be important in the pathogenesis of H pylori gastritis or carcinogenesis, or both. PMID:8566844
Sancar, Mesut; Izzettin, Fikret Vehbi; Apikoglu-Rabus, Sule; Besisik, Fatih; Tozun, Nurdan; Dulger, Gul
Helicobacter pylori is the most important etiologic agent for development of peptic ulcer, chronic gastritis and gastric carcinomas. It is now well established that H. pylori eradication treatment is more cost-effective than acid suppressing therapies alone for the treatment of peptic ulcer disease. However, the comparative cost-effectiveness of various H. pylori eradication regimens is still not clear. This study was designed to make a pharmacoeconomic comparison of different H. pylori eradication regimens in patients with peptic ulcer disease or chronic gastritis, using real-world cost and effectiveness data. Istanbul University Hospital and Marmara University Hospital. A total of 75 patients diagnosed as H. pylori (+) by endoscopy were randomized to receive one of the seven H. pylori treatment protocols. These protocols were as follows: (LAC) = 'lansoprazole 30 mg bid + amoxicillin 1 g bid + clarithromycin 500 mg bid' for 7 days and (OCM) = 'omeprazole 20 mg bid + clarithromycin 250 mg bid + metronidazole 500 mg bid'; (OAM) = 'omeprazole 40 mg qd + amoxicillin 500 mg tid + metronidazole 500 mg tid'; (MARB) = 'metronidazole 250 mg tid + amoxicillin 500 mg qid + ranitidine 300 mg hs + bismuth 300 mg qid'; (OAC) = omeprazole 20 mg bid + amoxicillin 1 g bid + clarithromycin 500 mg bid'; (OCA) = omeprazole 40 mg bid + clarithromycin 500 mg bid + amoxicillin 1 g bid'; (OAB) = 'omeprazole 20 mg bid + amoxicillin 500 mg tid + bismuth 300 mg qid' each for 14 days. Only direct costs were included in the analysis. Effectiveness was measured in terms of "successful eradication". The cost-effectiveness ratios of the regimens were calculated using these effectiveness and cost data. The perspective of the study was assumed as the Government's perspective. Cost-effectiveness ratios of eradication regimens. MARB and OCA regimens were found to be more cost-effective than the other treatment regimens. The eradication rates and cost-effectiveness ratios calculated for these
Aghili, Rokhsareh; Jafarzadeh, Faria; Ghorbani, Raheb; Khamseh, Mohammad Ebrahim; Salami, Maryam Alsadat; Malek, Mojtaba
Autoimmune thyroid diseases (ATD) are multifactorial conditions that result from genetic predisposition in combination with environmental risk factors. Helicobacter pylori infection as an environmental risk factor has been proposed to imitate the antigenic components of the thyroid cell membrane and may play a leading role in the onset of the autoimmune diseases, such as Hashimoto thyroiditis. The aim of this study was to investigate the association between Helicobacter pylori (HP) infection and Hashimoto's thyroiditis (HT). The participants in this case-control study included 43 patients affected by Hashimoto's thyroiditis, and 40 healthy individuals without history of autoimmune disease as the control group. Anti HP IgG and anti-TPO antibodies were determined using ELISA method. Results were considered positive when the IgG anti-HP value was higher than 30 IU/ml and the anti-TPO autoantibody value was higher than 75 IU/ml. The mean TSH level was 18.3±16.8 IU/ml for patients and 2.8±1.2 IU/ml for the control group (P<0.001). 46.5% of the patient group and 10.8% of the control group were infected with HP. The association between HP and Hashimoto's thyroiditis was statistically significant (Odds Ratio=7.2, 95%, Confidence Interval: 2.0- 28.8, P<0.001). The findings show that, there is an association between HP and Hashimoto's thyroiditis. To establish a definite correlation between them, more detailed studies with a more specialized examination and precise consideration regarding species of HP, genetic polymorphism of the host and investigation of environmental factors are needed.
Flahou, Bram; Haesebrouck, Freddy; Smet, Annemieke; Yonezawa, Hideo; Osaki, Takako; Kamiya, Shigeru
A substantial number of reports published in the last year have contributed to a better understanding of both human and animal infection with non-Helicobacter pylori Helicobacter species (NHPH). Gastric infection of humans with Helicobacter suis and Helicobacter felis as well as unidentified NHPH has been described to cause a chronic gastritis and a variety of clinical symptoms, whereas enterohepatic NHPH, including Helicobacter cinaedi, Helicobacter bilis, and Helicobacter canis, have been reported to be associated with human diseases such as bacteremia, cellulitis, cutaneous diseases, and fever of unknown origin in immunocompromised hosts. In various animal species, including dogs and laboratory mice, high rates of infection with NHPH were described. For gastric NHPH, mainly H. suis and H. felis infection was studied, revealing that differences in the immune response evoked in the host do exist when compared to Helicobacter pylori. Pathogenic mechanisms of infection with Helicobacter pullorum, H. bilis, and Helicobacter hepaticus were investigated, as well as immune responses involved in H. bilis-, Helicobacter typhlonius-, and H. hepaticus-induced intestinal inflammation. Complete genome sequences of Helicobacter heilmannii strain ASB1 and a H. cinaedi strain isolated in a case of human bacteremia were published, as well as comparative genomics of a human-derived Helicobacter bizzozeronii strain and proteome or secretome analyses for H. hepaticus and Helicobacter trogontum, respectively. Molecular analysis has revealed a function for type VI secretion systems of H. hepaticus and H. pullorum, the Helicobacter mustelae iron urease, and several other functional components of NHPH. In each section of this chapter, new findings on gastric NHPH will first be discussed, followed by those on enterohepatic Helicobacter species.
Nordenstedt, Helena; Graham, David Y.; Kramer, Jennifer R.; Rugge, Massimo; Verstovsek, Gordana; Fitzgerald, Stephanie; Alsarraj, Abeer; Shaib, Yasser; Velez, Maria E.; Abraham, Neena; Anand, Bhupinderjit; Cole, Rhonda; El-Serag, Hashem B.
OBJECTIVES Recent studies using histology alone in select patients have suggested that Helicobacter pylori-negative gastritis may be common. The objective of this study was to investigate the prevalence of H. pylori among individuals with histologic gastritis. METHODS Subjects between 40 and 80 years underwent elective esophagogastroduodenoscopy at a VA Medical Center. Gastric biopsies were mapped from seven prespecified sites (two antrum, four corpus, and one cardia) and graded by two gastrointestinal pathologists, using the Updated Sydney System. H. pylori-negative required four criteria: negative triple staining at all seven gastric sites, negative H. pylori culture, negative IgG H. pylori serology, and no previous treatment for H. pylori. Data regarding tobacco smoking, alcohol drinking, nonsteroidal anti-inflammatory drug, and proton pump inhibitor (PPI) use were obtained by questionnaire. RESULTS Of the 491 individuals enrolled, 40.7% (200) had gastritis of at least grade 2 in at least one biopsy site or grade 1 in at least two sites. Forty-one (20.5%) had H. pylori-negative gastritis; most (30 or 73.2%) had chronic gastritis, five (12.2%) had active gastritis, and six (14.6%) had both. H. pylori-negative gastritis was approximately equally distributed in the antrum, corpus, and both antrum and corpus. Past and current PPI use was more frequent in H. pylori-negative vs. H. pylori-positive gastritis (68.2% and 53.8%; P = 0.06). CONCLUSIONS We used multiple methods to define non-H. pylori gastritis and found it in 21% of patients with histologic gastritis. While PPI use is a potential risk factor, the cause or implications of this entity are not known. PMID:23147524
Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł
Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor.
Chung, Yun Hee; Gwak, Jong Seop; Hong, Sung Woo; Hyeon, Jung Hyeon; Lee, Cheol Min; Oh, Seung Won
Background Helicobacter pylori (H. pylori) infection may cause systemic inflammation and increase the production of tumor necrosis factor-α, interleukin-1, and interleukin-6. Unfortunately, bone mineral density also may be affected by these cytokines. This study aimed to evaluate the association between bone mineral density and H. pylori infection. Methods A cross-sectional study evaluated 1,126 men undergoing a comprehensive health screening in a private Korean screening center. Subjects' sera were tested for H. pylori antibodies (immunoglobulin G) using an enzyme-linked immunosorbent assay, and bone mineral densities (g/cm2) of the lumbar spine, femoral neck, and total femur were obtained using dual-energy X-ray absorptiometry. To evaluate the difference in bone mineral density according to H. pylori infection status, the adjusted mean bone mineral densities at each site were compared after adjusting for potential confounders, including age, sex, body mass index, smoking, alcohol consumption, and exercise. Results H. pylori infection was associated with a significant decrease in mean lumbar bone mineral density (H. pylori-positive, 1.190 g/cm2; H. pylori-negative, 1.219 g/cm2; P=0.006), which was greatest among men who were ≥50 years old (H. pylori-positive, 1.193 g/cm2; H. pylori-negative, 1.233 g/cm2; P=0.006). However, no significant association was observed in the bone mineral densities of the total femur and femoral neck. Conclusion In men, H. pylori infection was negatively associated with lumbar bone mineral density. This association may be useful in the early detection, prevention, and management of male osteoporosis. PMID:26435815
Veiga, Nélio; Pereira, Carlos; Resende, Carlos; Amaral, Odete; Ferreira, Manuela; Nelas, Paula; Chaves, Claudia; Duarte, João; Cirnes, Luis; Machado, José Carlos; Ferreira, Paula; Correia, Ilídio J.
Introduction This study consisted in the comparison of the prevalence of Helicobacter pylori (H. pylori) present in the stomach and in saliva of a sample of Portuguese adolescents and the assessment of the association between H. pylori infection with socio-demographic variables and prevalence of dental caries. Materials and Methods A cross-sectional study was designed including a sample of 447 adolescents aged 12 to 19 years old, attending a public school in Sátão, Portugal. A questionnaire about socio-demographic variables and oral health behaviors was applied. Gastric H. pylori infection was determined using the urease breath test (UBT). Saliva collection was obtained and DNA was extracted by Polymerase Chain Reaction (PCR) in order to detect the presence of oral H. pylori. Results The prevalence of gastric H. pylori detected by UBT was 35.9%. Within the adolescents with a gastric UBT positive, only 1.9% were positive for oral H. pylori. The presence of gastric H. pylori was found to be associated with age (>15years, Odds ratio (OR)=1.64,95%CI=1.08-2.52), residence area (urban,OR=1.48,95%CI=1.03-2.29) and parents´ professional situation (unemployed,OR=1.22,95%CI=1.02-1.23). Among those with detected dental caries during the intra-oral observation, 37.4% were positive for gastric H. pylori and 40.2% negative for the same bacterial strain (p=0.3). Conclusions The oral cavity cannot be considered a reservoir for infection of H. pylori. Gastric H. pylori infection was found to be associated with socio-demographic variables such as age, residence area and socioeconomic status. PMID:26010595
Shiota, Seiji; Cruz, Modesto; Abreu, José A. Jiménez; Mitsui, Takahiro; Terao, Hideo; Disla, Mildre; Iwatani, Shun; Nagashima, Hiroyuki; Matsuda, Miyuki; Uchida, Tomohisa; Tronilo, Lourdes; Rodríguez, Eduardo
Although the incidence of gastric cancer in the Dominican Republic is not high, the disease remains a significant health problem. We first conducted a detailed analysis of Helicobacter pylori status in the Dominican Republic. In total, 158 patients (103 females and 55 males; mean age 47.1±16.2 years) were recruited. The status of H. pylori infection was determined based on four tests: rapid urease test, culture test, histological test and immunohistochemistry. The status of cagA and vacA genotypes in H. pylori was examined using PCR and gene sequencing. The overall prevalence of H. pylori infection was 58.9 %. No relationship was found between the H. pylori infection rate and the age range of 17–91 years. Even in the youngest group (patients aged <29 years), the H. pylori infection rate was 62.5 %. Peptic ulcer was found in 23 patients and gastric cancer was found in one patient. The H. pylori infection rate in patients with peptic ulcer was significantly higher than that in patients with gastritis (82.6 versus 54.5 %, P<0.01). The cagA-positive/vacA s1m1 genotype was the most prevalent (43/64, 67.2 %). Compared with H. pylori-negative patients, H. pylori-positive patients showed more severe gastritis. Furthermore, the presence of cagA was related to the presence of more severe gastritis. All CagA-positive strains had Western-type CagA. In conclusion, we found that H. pylori infection is a risk factor for peptic ulcer in the Dominican Republic. Patients with cagA-positive H. pylori could be at higher risk for severe inflammation and atrophy. PMID:24965801
Shiota, Seiji; Cruz, Modesto; Abreu, José A Jiménez; Mitsui, Takahiro; Terao, Hideo; Disla, Mildre; Iwatani, Shun; Nagashima, Hiroyuki; Matsuda, Miyuki; Uchida, Tomohisa; Tronilo, Lourdes; Rodríguez, Eduardo; Yamaoka, Yoshio
Although the incidence of gastric cancer in the Dominican Republic is not high, the disease remains a significant health problem. We first conducted a detailed analysis of Helicobacter pylori status in the Dominican Republic. In total, 158 patients (103 females and 55 males; mean age 47.1±16.2 years) were recruited. The status of H. pylori infection was determined based on four tests: rapid urease test, culture test, histological test and immunohistochemistry. The status of cagA and vacA genotypes in H. pylori was examined using PCR and gene sequencing. The overall prevalence of H. pylori infection was 58.9 %. No relationship was found between the H. pylori infection rate and the age range of 17-91 years. Even in the youngest group (patients aged <29 years), the H. pylori infection rate was 62.5 %. Peptic ulcer was found in 23 patients and gastric cancer was found in one patient. The H. pylori infection rate in patients with peptic ulcer was significantly higher than that in patients with gastritis (82.6 versus 54.5 %, P<0.01). The cagA-positive/vacA s1m1 genotype was the most prevalent (43/64, 67.2 %). Compared with H. pylori-negative patients, H. pylori-positive patients showed more severe gastritis. Furthermore, the presence of cagA was related to the presence of more severe gastritis. All CagA-positive strains had Western-type CagA. In conclusion, we found that H. pylori infection is a risk factor for peptic ulcer in the Dominican Republic. Patients with cagA-positive H. pylori could be at higher risk for severe inflammation and atrophy. © 2014 The Authors.
Vasapolli, Riccardo; Malfertheiner, Peter; Kandulski, Arne
Peptic ulcer disease (PUD) has been further decreased over the last decades along with decreasing prevalence of Helicobacter pylori-associated PUD. A delayed H. pylori eradication has been associated with an increased risk of rehospitalization for complicated recurrent peptic ulcer and reemphasized the importance of eradication especially in patients with peptic ulcer bleeding (PUB). PUB associated with NSAID/aspirin intake and H. pylori revealed an additive interaction in gastric pathophysiology which favors the "test-and-treat" strategy for H. pylori in patients with specific risk factors. The H. pylori-negative and NSAID-negative "idiopathic PUD" have been increasingly observed and associated with slower healing tendency, higher risk of recurrence, and greater mortality. Helicobacter pylori-associated dyspepsia has been further investigated and finally defined by the Kyoto consensus. Helicobacter pylori eradication therapy is advised as first option in this group of patients. Only in the case of symptom persistence or recurrence after eradication therapy, dyspeptic patients should be classified as functional dyspepsia (FD). There were few new data in 2015 on the role of H. pylori infection in gastroesophageal reflux disease (GERD), and in particular Barrett's esophagus. A lower prevalence of gastric atrophy with less acid output in patients with erosive esophagitis confirmed previous findings. In patients with erosive esophagitis, no difference was observed in healing rates neither between H. pylori-positive and H. pylori-negative patients nor between patients that underwent eradication therapy compared to patients without eradication. These findings are in line with the current consensus guidelines concluding that H. pylori eradication has no effects on symptoms and does not aggravate preexisting GERD.
Sipponen, P.; Kosunen, T. U.; Valle, J.; Riihelä, M.; Seppälä, K.
AIMS: To investigate the prevalence of Helicobacter pylori associated chronic gastritis in patients with gastric cancer. METHODS: Serum IgG antibodies for H pylori were determined in 54 consecutive patients with gastric carcinoma. The prevalence of H pylori in gastric mucosa was also examined histologically (modified Giemsa) in 32 patients from whom adequate biopsy specimens of the antrum and corpus were available. Thirty five patients with gastrointestinal tumours outside the stomach and 48 with non-gastrointestinal malignancies served as controls. RESULTS: Of the 54 patients, 38 (70%) had H pylori antibodies (IgG) in their serum (three additional patients had H pylori antibodies IgA, class specific but not IgG specific). This prevalence was significantly higher (p less than 0.05) than that (49%) in the 35 controls. No differences in prevalence of H pylori antibodies were found between gastric cancer cases of intestinal (IGCA) or diffuse (DGCA) type, both these types showing H pylori antibodies (IgG) in 71% of the patients. In the subgroup of 32 subjects, five patients had normal gastric mucosa and four showed corpus limited atrophy ("pernicious anaemia type" atrophy of type A). All of these nine patients had no evidence of current or previous H pylori infection in serum (no IgG antibodies) or in tissue sections (negative Giemsa staining). The remaining 23 patients had antral or pangastritis, and all had evidence of current or previous H pylori infection. CONCLUSIONS: H pylori associated chronic gastritis was the associated disease in 75% of the patients with gastric cancer occurring equally often in both IGCA and DGCA groups. About 25% of cases seem to have a normal stomach or severe corpus limited atrophy, neither of which showed evidence of concomitant H pylori infection. PMID:1577969
Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł
Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor. PMID:28321154
Román-Román, Adolfo; Giono-Cerezo, Silvia; Camorlinga-Ponce, Margarita; Martínez-Carrillo, Dinorah Nashely; Loaiza-Loeza, Salome; Fernández-Tilapa, Gloria
Helicobacter pylori adheres to various components of the human saliva. Therefore, the objective of this research was to simultaneously detect H. pylori in saliva and in gastric biopsy, and to determine the agreement between the vacA genotypes in both saliva and gastric biopsy. A total of 162 patients with chronic gastritis and 34 with gastric ulcer were studied, and saliva and biopsy samples were collected from each patient. H. pylori DNA was detected by conventional PCR and nested PCR was used for vacA genotyping. In 24% of the patients (47/196) H. pylori DNA was found in saliva and in biopsy; 52.5% (103/196) were saliva(negative)/biopsy(positive) and 6.6% (13/196) were saliva(positive)/biopsy(negative). In either or both H. pylori vacAs1m1 or s1m2 genotypes were detected in saliva in 41.5% of the patients with chronic gastritis. Forty-seven percent had >1 genotype, and the s1m1/s1m2 combination was found in 36% of them. H. pylori vacAs1m1 and s1m2 were also found in the saliva and biopsy of patients with gastric ulcer. The genotypes found in saliva and biopsy of the same patient had 51.1% agreement. In 27.6% of the 47 patients saliva(positive)/biopsy(positive) two genotypes were found in saliva, and one or both in the stomach. The s1m1/s1m2 genotypes, alone or together, are found simultaneously in saliva and gastric biopsy of the same patient. These results suggest that H. pylori reaches the oral cavity by various ways, and that saliva can be the transmitting and re-infecting vector. Copyright © 2012 Elsevier España, S.L. All rights reserved.
Nielsen, H; Andersen, L P
The immunopathology of Helicobacter pylori associated active chronic gastritis, which is characterised by predominance of polymorphonuclear leucocyte infiltration, is largely unknown. To evaluate the role of bacterial components as inflammatory mediators ultracentrifuged sonicated preparations were made of clinical isolates of Helicobacter pylori. The crude sonicates were shown to exhibit chemotactic activity for human polymorphonuclear leucocytes and blood monocytes in a concentration dependent fashion. The potency was comparable with previously described bacterial derived cytotaxins. The cytotaxin(s) was non-dialysable and completely destroyed by proteinase. Heat treatment did not decrease the chemotactic activity, but in sonicate subjected to 100 degrees C for 15 minutes all activity disappeared after dialysis suggesting the breakdown of a larger protein to small fragments that are still biological active. By ammonium sulphate precipitation at increasing concentrations the cytotaxin(s) was selectively found in 10% ammonium sulphate saturation, and by further molecular gel separation the chemotactic activity was found in the molecular size range from 25 to 35 kDa. The demonstration of a polymorphonuclear leucocyte and monocyte cytotaxin from Helicobacter pylori sonicate may help in understanding the mucosal immune response in gastric inflammatory diseases. PMID:1624151
Fahey, Jed W.; Stephenson, Katherine K.; Wade, Kristina L.; Talalay, Paul
Infections by Helicobacter pylori are very common, causing gastroduodenal inflammation including peptic ulcers, and increasing the risk of gastric neoplasia. The isothiocyanate (ITC) sulforaphane [SF; 1-isothiocyanato-4-(methylsulfinyl)butane] derived from edible crucifers such as broccoli is potently bactericidal against Helicobacter, including antibiotic-resistant strains, suggesting a possible dietary therapy. Gastric H. pylori infections express high urease activity which generates ammonia, neutralizes gastric acidity, and promotes inflammation. The finding that SF inhibits (inactivates) urease (jack bean and Helicobacter) raised the issue of whether these properties might be functionally related. The rates of inactivation of urease activity depend on enzyme and SF concentrations and show first order kinetics. Treatment with SF results in time-dependent increases in the ultraviolet absorption of partially purified Helicobacter urease in the 280–340 nm region. This provides direct spectroscopic evidence for the formation of dithiocarbamates between the ITC group of SF and cysteine thiols of urease. The potencies of inactivation of Helicobacter urease by isothiocyanates structurally related to SF were surprisingly variable. Natural isothiocyanates closely related to SF, previously shown to be bactericidal (berteroin, hirsutin, phenethyl isothiocyanate, alyssin, and erucin), did not inactivate urease activity. Furthermore, SF is bactericidal against both urease positive and negative H. pylori strains. In contrast, some isothiocyanates such as benzoyl-ITC, are very potent urease inactivators, but are not bactericidal. The bactericidal effects of SF and other ITC against Helicobacter are therefore not obligatorily linked to urease inactivation, but may reduce the inflammatory component of Helicobacter infections. PMID:23583386
Reigh, Shang-Yik; Lauga, Eric
Swimming microorganisms and self-propelled nanomotors are often found in confined environments. The bacterium Helicobacter pylori survives in the acidic environment of the human stomach and is able to penetrate gel-like mucus layers and cause infections by locally changing the rheological properties of the mucus from gel-like to solution-like. In this talk we propose an analytical model for the locomotion of Helicobacter pylori as a confined spherical squirmer which generates its own confinement. We solve analytically the flow field around the swimmer, and derive the swimming speed and energetics. The role of the boundary condition in the outer wall is discussed. An extension of our model is also proposed for other biological and chemical swimmers. Newton Trust.
Yamaoka, Yoshio; Graham, David Y
Helicobacter pylori is human gastric pathogen that causes chronic and progressive gastric mucosal inflammation and is responsible for the gastric inflammation-associated diseases, gastric cancer and peptic ulcer disease. Specific outcomes reflect the interplay between host-, environmental- and bacterial-specific factors. Progress in understanding putative virulence factors in disease pathogenesis has been limited and many false leads have consumed scarce resources. Few in vitro-in vivo correlations or translational applications have proved clinically relevant. Reported virulence factor-related outcomes reflect differences in relative risk of disease rather than specificity for any specific outcome. Studies of individual virulence factor associations have provided conflicting results. Since virulence factors are linked, studies of groups of putative virulence factors are needed to provide clinically useful information. Here, the authors discuss the progress made in understanding the role of H. pylori virulence factors CagA, vacuolating cytotoxin, OipA and DupA in disease pathogenesis and provide suggestions for future studies.
Engstrand, Lars; Lindberg, Mathilda
The human microbiota along the gastrointestinal tract is currently extensively studied and a number of studies focuses on elucidating the association between a more or less diverse intestinal microbial community and health and disease. The human stomach is considered to be exclusively inhabited by Helicobacter pylori and further lacks a colonizing non-H. pylori bacterial flora due to the acidic environment. However, recently a limited number of studies using molecular-based methods have provided a broader picture of the stomach microbiota. The question is whether changes in gastric pH or antibiotic treatment can lead to significant shifts in the stomach microbiota that may be involved in disease development such as gastric cancer. Copyright © 2013. Published by Elsevier Ltd.
Lazaridou, Elizabeth; Korfitis, Chrysovalantis; Kemanetzi, Christina; Sotiriou, Elena; Apalla, Zoe; Vakirlis, Efstratios; Fotiadou, Christina; Lallas, Aimilios; Ioannides, Demetrios
Rosacea is a chronic skin disease characterized by facial erythema and telangiectasia. Despite the fact that many hypotheses have been proposed, its etiology remains unknown. In the present review, the possible link and clinical significance of Helicobacter pylori in the pathogenesis of rosacea are being sought. A PubMed and Google Scholar search was performed using the terms “rosacea”, “H.pylori”, “gastrointestinal disorders and H.pylori”, “microorganisms and rosacea”, “pathogenesis and treatment of rosacea”, and “risk factors of rosacea”, and selected publications were studied and referenced in text. Although a possible pathogenetic link between H. pylori and rosacea is advocated by many authors, evidence is still interpreted differently by others. We conclude that further studies are needed in order to fully elucidate the pathogenesis of rosacea. PMID:28848358
Background Extensive genetic diversity and rapid allelic diversification are characteristics of the human gastric pathogen Helicobacter pylori, and are believed to contribute to its ability to cause chronic infections. Both a high mutation rate and frequent imports of short fragments of exogenous DNA during mixed infections play important roles in generating this allelic diversity. In this study, we used a genetic approach to investigate the roles of nucleotide excision repair (NER) pathway components in H. pylori mutation and recombination. Results Inactivation of any of the four uvr genes strongly increased the susceptibility of H. pylori to DNA damage by ultraviolet light. Inactivation of uvrA and uvrB significantly decreased mutation frequencies whereas only the uvrA deficient mutant exhibited a significant decrease of the recombination frequency after natural transformation. A uvrC mutant did not show significant changes in mutation or recombination rates; however, inactivation of uvrC promoted the incorporation of significantly longer fragments of donor DNA (2.2-fold increase) into the recipient chromosome. A deletion of uvrD induced a hyper-recombinational phenotype. Conclusions Our data suggest that the NER system has multiple functions in the genetic diversification of H. pylori, by contributing to its high mutation rate, and by controlling the incorporation of imported DNA fragments after natural transformation. PMID:22559785
Doorakkers, Eva; Lagergren, Jesper; Gajulapuri, Vijaya Krishna; Callens, Steven; Engstrand, Lars; Brusselaers, Nele
Helicobacter pylori is associated with peptic ulcers and gastric cancer and its eradication aims to prevent these conditions. The recommended eradication regimen is triple therapy, consisting of a proton-pump inhibitor in combination with clarithromycin and amoxicillin or metronidazole for 7 days. Yet, other antibiotic regimens are sometimes prescribed. We aimed to assess the use of eradication therapy for H. pylori in the Swedish population during the last decade. This population-based study used data from the Swedish Prescribed Drug Register. From July 2005 until December 2014, all regimens that can eradicate H. pylori were identified and evaluated according to patients' age and sex and calendar year of eradication. We identified 157,915 eradication episodes in 140,391 individuals (53.8% women, 42.6% older than 60 years), who correspond to 1.5% of the Swedish population. The absolute number and incidence of eradications decreased over the study period. Overall, 91.0% had one eradication and 0.1% had more than three. Of all eradications, 95.4% followed the recommended regimen, while 4.7% did not. The latter group was overrepresented among individuals aged ≥80 years (7.8%). Amoxicillin and clarithromycin were most frequently prescribed, while metronidazole was rarely used (0.01%). Other prescribed antibiotics were ciprofloxacin (2.4%), doxycycline (1.4%), nitrofurantoin (0.7%), norfloxacin (0.5%) and erythromycin (0.3%). During the last decade in Sweden H. pylori eradication has been frequently prescribed, but the incidence of eradication has slowly declined. Most eradications followed the recommended regimen, including those occurring after a previous eradication.
Helicobacter pylori, a gastric pathogen, is known to be associated with gastric and duodenal ulcers, and is also a strong risk factor for the development of gastric cancer and lymphoma of the mucosal-associated lymphoid tissue. Ordinarily, this should make a strong case for its eradication at par with any other infectious disease. However, the unique biology of H. pylori and the complexity of its interactions with humans, its only known natural host, do not permit the recommendation of unambiguous preventive and therapeutic measures. Moreover, this organism has co-evolved with humans as a practically universal member of the natural gastric microbiota over at least 100,000 years. H. pylori persists for a lifetime in mostly asymptomatic hosts, and causes clinical disease only in a minority of infections. Therefore, its potential contribution to the maintenance of human immune homeostasis, as is the case with the better-studied members of the intestinal microbiota, is certainly worthy of serious investigation. In this paper, we summarize some interesting and often anecdotal data drawn from recent studies, and examine their significance in the context of the hygiene hypothesis. We also examine whether the lower incidence of gastric cancer over large parts of the world in spite of a high prevalence of infection (the Asian and African enigmas) may be re-interpreted in terms of the hygiene hypothesis. Finally, it is suggested that an evolutionary-ecological approach to the study of H. pylori infection may help in the formulation of strategies for the management of this infection. This may well be an infectious disease wherein medical interventions may have to be personalized to ensure optimal outcomes.
Szadkowski, Aleksander; Chojnacki, Jan; Klupińska, Grazyna; Wojtuń, Stanisław
Numerous medical reports claim that the effectiveness of H. pylori therapy decreases. The aim of the study was the analysis of the reasons of this phenomenon on own material. The study included 437 subjects, aged 19-64 years with chronic gastritis with H. pylori infection. All patients were subjected to: endoscopy, fast urease test, breath test (UBT-13C) and antibody titer in IgG class was determined. In the case of ineffective therapy bacteriological examination was performed. In the first stage of the therapy pantoprazol (2 x 40 mg) and amoxicillin (2 x 1000 mg) with metronidazol (2 x 500 mg) were applied in 282 subjects for 7 days (group I), amoxicillin with clarithromycin (2 x 500 mg) in 182 subjects (group II) and clarithromycin with metronidazol in 43 subjects (group III). After 6 weeks negative breath test was observed on average in 65.68% without significant differences between the groups. Ineffective therapy was more frequent in subjects over 45 years of age with high intensity of H. pylori colonization and earlier treated with antibiotics due to other reasons; such differences were not observed dependently on the antibody titer. In the second stage of the therapy pantoprazol was still administered but antibacterial drugs were changed among the groups. From among 150 subjects eradication was obtained in 117 (78.0%). In 33 subjects with ineffective therapy bacteriological examination of gastric bioptates confirmed antibiotic resistance in 75.76%. It results from the study that the applied therapy, consistent with current recommendations of the experts, does not ensure H. pylori eradication in part of the patients, what points to the necessity of searching for other effective antibiotics.
Background Helicobacter pylori is the causative agent for gastritis, and peptic and duodenal ulcers. The bacterium displays 5-6 polar sheathed flagella that are essential for colonisation and persistence in the gastric mucosa. The biochemistry and genetics of flagellar biogenesis in H. pylori has not been fully elucidated. Bioinformatics analysis suggested that the gene HP0256, annotated as hypothetical, was a FliJ homologue. In Salmonella, FliJ is a chaperone escort protein for FlgN and FliT, two proteins that themselves display chaperone activity for components of the hook, the rod and the filament. Results Ablation of the HP0256 gene in H. pylori significantly reduced motility. However, flagellin and hook protein synthesis was not affected in the HP0256 mutant. Transmission electron transmission microscopy revealed that the HP0256 mutant cells displayed a normal flagellum configuration, suggesting that HP0256 was not essential for assembly and polar localisation of the flagella in the cell. Interestingly, whole genome microarrays of an HP0256 mutant revealed transcriptional changes in a number of genes associated with the flagellar regulon and the cell envelope, such as outer membrane proteins and adhesins. Consistent with the array data, lack of the HP0256 gene significantly reduced adhesion and the inflammatory response in host cells. Conclusions We conclude that HP0256 is not a functional counterpart of FliJ in H. pylori. However, it is required for full motility and it is involved, possibly indirectly, in expression of outer membrane proteins and adhesins involved in pathogenesis and adhesion. PMID:20377912
Wang, Ge; Hong, Yang; Olczak, Adriana; Maier, Susan E; Maier, Robert J
Neutrophil-activating protein (NapA) has been well documented to play roles in human neutrophil recruitment and in stimulating host cell production of reactive oxygen intermediates (ROI). A separate role for NapA in combating oxidative stress within H. pylori was implied by studies of various H. pylori mutant strains. Here, physiological analysis of a napA strain was the approach used to assess the iron-sequestering and stress resistance roles of NapA, its role in preventing oxidative DNA damage, and its importance to mouse colonization. The napA strain was more sensitive to oxidative stress reagents and to oxygen, and it contained fourfold more intracellular free iron and more damaged DNA than the parent strain. Pure, iron-loaded NapA bound to DNA, but native NapA did not, presumably linking iron levels sensed by NapA to DNA damage protection. Despite its in vitro phenotype of sensitivity to oxidative stress, the napA strain showed normal (like that of the wild type) mouse colonization efficiency in the conventional in vivo assay. By use of a modified mouse inoculation protocol whereby nonviable H. pylori is first inoculated into mice, followed by (live) bacterial strain administration, an in vivo role for NapA in colonization efficiency could be demonstrated. NapA is the critical component responsible for inducing host-mediated ROI production, thus inhibiting colonization by the napA strain. An animal colonization experiment with a mixed-strain infection protocol further demonstrated that the napA strain has significantly decreased ability to survive when competing with the wild type. H. pylori NapA has unique and separate roles in gastric pathogenesis.
Jones, M D; Ademi, I; Yin, X; Gong, Y; Zamble, D B
Nickel is an essential transition metal for the survival of Helicobacter pylori in the acidic human stomach. The nickel-responsive transcriptional regulator HpNikR is important for maintaining healthy cytosolic nickel concentrations through the regulation of multiple genes, but its complete regulon and role in nickel homeostasis are not well understood. To investigate potential gene targets of HpNikR, ChIP sequencing was performed using H. pylori grown at neutral pH in nickel-supplemented media and this experiment identified HPG27_866 (frpB2) and HPG27_1499 (ceuE). These two genes are annotated to encode a putative iron transporter and a nickel-binding, periplasmic component of an ABC transporter, respectively. In vitro DNA-binding assays revealed that HpNikR binds both gene promoter sequences in a nickel-responsive manner with affinities on the order of ∼10(-7) M. The recognition sites of HpNikR were identified and loosely correlate with the HpNikR pseudo-consensus sequence (TATTATT-N11-AATAATA). Quantitative PCR experiments revealed that HPG27_866 and HPG27_1499 are transcriptionally repressed following growth of H. pylori G27 in nickel-supplemented media, and that this response is dependent on HpNikR. In contrast, iron supplementation results in activation of HPG27_1499, but no impact on the expression of HPG27_866 was observed. Metal analysis of the Δ866 strain revealed that HPG27_866 has an impact on nickel accumulation. These studies demonstrate that HPG27_866 and HPG27_1499 are both direct targets of HpNikR and that HPG27_866 influences nickel uptake in H. pylori.
Voss, Bradley J.; Gaddy, Jennifer A.; McDonald, W. Hayes
More than 50 Helicobacter pylori genes are predicted to encode outer membrane proteins (OMPs), but there has been relatively little experimental investigation of the H. pylori cell surface proteome. In this study, we used selective biotinylation to label proteins localized to the surface of H. pylori, along with differential detergent extraction procedures to isolate proteins localized to the outer membrane. Proteins that met multiple criteria for surface-exposed outer membrane localization included known adhesins, as well as Cag proteins required for activity of the cag type IV secretion system, putative lipoproteins, and other proteins not previously recognized as cell surface components. We identified sites of nontryptic cleavage consistent with signal sequence cleavage, as well as C-terminal motifs that may be important for protein localization. A subset of surface-exposed proteins were highly susceptible to proteolysis when intact bacteria were treated with proteinase K. Most Hop and Hom OMPs were susceptible to proteolysis, whereas Hor and Hof proteins were relatively resistant. Most of the protease-susceptible OMPs contain a large protease-susceptible extracellular domain exported beyond the outer membrane and a protease-resistant domain at the C terminus with a predicted β-barrel structure. These features suggest that, similar to the secretion of the VacA passenger domain, the N-terminal domains of protease-susceptible OMPs are exported through an autotransporter pathway. Collectively, these results provide new insights into the repertoire of surface-exposed H. pylori proteins that may mediate bacterium-host interactions, as well as the cell surface topology of these proteins. PMID:24769695
Goh, Khean-Lee; Chan, Wah-Kheong; Shiota, Seiji; Yamaoka, Yoshio
This review summarizes studies on the epidemiology and public health implications of Helicobacter pylori published in peer-reviewed journals from April 2010 through March 2011. Prevalence rates vary widely between different geographical regions and ethnic groups. An interesting study from the USA identified the degree of African ancestry as an independent predictor of H. pylori infection. Two studies have demonstrated early childhood as the period of transmission of infection and identified an infected sibling as an important risk factor. An oral–oral route of spread has been substantiated with several studies showing the presence of H. pylori in the oral cavity. Studies have shown the presence of H. pylori in drinking water and the role of poor living conditions and sanitation in H. pylori infection, supporting an oral–fecal route of spread. Screening for H. pylori as a gastric cancer prescreening strategy has been described in Japan, and the importance of H. pylori eradication as a gastric cancer–prevention strategy has now been further emphasized in Japanese guidelines. Two studies have shown a decrease in the burden of dyspepsia and peptic ulcer disease with H. pylori eradication. PMID:21896079
Kumar, Narender; Albert, M John; Al Abkal, Hanan; Siddique, Iqbal; Ahmed, Niyaz
Helicobacter pylori, the human gastric pathogen, causes a variety of gastric diseases ranging from mild gastritis to gastric cancer. While the studies on H. pylori are dominated by those based on either East Asian or Western strains, information regarding H. pylori strains prevalent in the Middle East remains scarce. Therefore, we carried out whole-genome sequencing and comparative analysis of three H. pylori strains isolated from three native Arab, Kuwaiti patients. H. pylori strains were sequenced using Illumina platform. The sequence reads were filtered and draft genomes were assembled and annotated. Various pathogenicity-associated regions and phages present within the genomes were identified. Phylogenetic analysis was carried out to determine the genetic relatedness of Kuwaiti strains to various lineages of H. pylori. The core genome content and virulence-related genes were analyzed to assess the pathogenic potential. The three genomes clustered along with HpEurope strains in the phylogenetic tree comprising various H. pylori lineages. A total of 1187 genes spread among various functional classes were identified in the core genome analysis. The three genomes possessed a complete cagPAI and also retained most of the known outer membrane proteins as well as virulence-related genes. The cagA gene in all three strains consisted of an AB-C type EPIYA motif. The comparative genomic analysis of Kuwaiti H. pylori strains revealed a European ancestry and a high pathogenic potential. © 2016 John Wiley & Sons Ltd.
Helicobacter pylori and Aeromonas hydrophila are contaminants listed on the USEPA's 1998 Contaminant Candidate List (CCL).The sensitivity of H. pylori to chlorine and of Aeromonas spp. to inactivation by free chlorine, chloramine and ultraviolet (UV) was examined. Selective and...
A few reports have been written stating that H. pylori can be found in waters. However, detection and identification of H. pylori from water samples remains a very difficult task. One method that seems to work successfully is immunomagnetic capture. Water samples were concentr...
The mode by which Helicobacter pylori, the causative agent of most gastric ulcers, is transmitted remains undetermined. Epidemiological evidence suggests these organisms are waterborne; however, H. pylori has rarely been grown from potential water sources. This may be due to th...
The mode by which Helicobacter pylori, the causative agent of most gastric ulcers, is transmitted remains undetermined. Epidemiological evidence suggests these organisms are waterborne; however, H. pylori has rarely been grown from potential water sources. This may be due to th...
Velapatiño, Billie; Balqui, Jacqueline; Gilman, Robert H.; Bussalleu, Alejandro; Quino, Willi; Finger, S. Alison; Santivañez, Livia; Herrera, Phabiola; Piscoya, Alejandro; Valdivia, Jose; Cok, Jaime; Berg, Douglas E.
The method of recovering Helicobacter pylori DNA or viable cells absorbed on a string that a person has swallowed and that is retrieved an hour later (string test) should be a useful alternative to traditional analysis of cells or DNA obtained by endoscopy, which is invasive, uncomfortable, relatively costly, and ill-suited for community-based and pediatric studies. Here we assayed the sensitivity and validity of the string test versus conventional endoscopic biopsy for detecting and analyzing H. pylori infection. Forty-four people with gastric complaints were studied using both H. pylori culture and urease gene (ureB) PCR. H. pylori organisms cultured from strings and biopsy specimens from the same patients were fingerprinted by the randomly amplified polymorphic DNA (RAPD) method. Biopsy sections were also hematoxylin and eosin and silver stained for H. pylori detection. H. pylori was cultured from 80% of strings and detected by PCR from 91% of strings from participants whose biopsies had been H. pylori positive by culture, PCR, and/or histology. Strains recovered from strings and biopsy specimens yielded identical or closely related RAPD profiles in each of the 24 cases tested. We conclude that the string test is a useful method for H. pylori recovery and analysis when relatively noninvasive procedures are needed. PMID:16517886
Adler, Isabel; Muiño, Andrea; Aguas, Silvia; Harada, Laura; Diaz, Mariana; Lence, Adriana; Labbrozzi, Mario; Muiño, Juan Manuel; Elsner, Boris; Avagnina, Alejandra; Denninghoff, Valeria
Helicobacter pylori (H. pylori) has been found in the oral cavity and stomach, and its infection is one of the most frequent worldwide. We reviewed the literature and conducted a Topic Highlight, which identified studies reporting an association between H. pylori-infection in the oral cavity and H. pylori-positive stomach bacterium. This work was designed to determine whether H. pylori is the etiologic agent in periodontal disease, recurrent aphthous stomatitis (RAS), squamous cell carcinoma, burning and halitosis. Record selection focused on the highest quality studies and meta-analyses. We selected 48 articles reporting on the association between saliva and plaque and H. pylori-infection. In order to assess periodontal disease data, we included 12 clinical trials and 1 meta-analysis. We evaluated 13 published articles that addressed the potential association with RAS, and 6 with squamous cell carcinoma. Fourteen publications focused on our questions on burning and halitosis. There is a close relation between H. pylori infection in the oral cavity and the stomach. The mouth is the first extra-gastric reservoir. Regarding the role of H. pylori in the etiology of squamous cell carcinoma, no evidence is still available.
Poveda, Gina Ferrer; Carrillo, Katia Sáez; Monje, Marcela Espinoza; Cruz, Carlos Alvarez; Cancino, Apolinaria García
the aim of this research was to determine the prevalence of Helicobacter pylori infection on Chilean pregnant women and its relationship with the appearance and severity of hyperemesis and dyspepsia. quantitative study of prevalence in a transversal cut with variable analysis. The sample was taken from 274 Chilean pregnant women from the Bío Bío province through vein puncture between June and December, 2005. Pregnant women were informed of this study, interviewed and signed an informed consent. The samples were processed using ImmunoComb II Helicobacter pylori IgG kit. Statistical analysis was performed by means of the Statistical Package for Social Sciences (SPSS) Program. out of the total number of pregnant women, 68.6% showed infection by Helicobacter pylori. 79.6% of the total sample had symptoms of dyspepsia, and 72.5% of this group presented Helicobacter pylori infection. 12.4% showed pregnancy hyperemesis; among them, 79.4% were infected with Helicobacter pylori. 73.4% of the pregnant women that showed gastric discomfort during the first three months had Helicobacter pylori infection. 53.7% of them continued with gastric discomfort after the first three months; of those, 95.8% were infected. Helicobacter pylori infection was present only in 1.5% of pregnant women without gastric discomfort. both, gastric discomfort of pregnant women and the continuity of severe symptoms of dyspepsia and hyperemesis after the first three months of gestation are significantly correlated with Helicobacter pylori infection.
Nevin, Daniel T; Morgan, Christopher J; Graham, David Y; Genta, Robert M
The risk factors for acquiring Helicobacter pylori and Human Immunodeficiency Virus (HIV) infections are different: H. pylori is transmitted by gastro- or fecal-oral routes and is associated with low socioeconomic conditions, while HIV is transmitted through sexual intercourse, infected body fluids, and transplacentally. If the host responses to these infections were independent, the prevalence of H. pylori should be similar in HIV-infected and non-infected patients. Yet, several studies have detected a lower prevalence of H. pylori in patients with HIV infection, whereas other studies found either no differences or greater rates of H. pylori infection in HIV-positive subjects. To review studies that addressed the issue of these two simultaneous infections and attempt to determine whether reliable conclusions can be drawn from this corpus of often contrasting evidence. Electronic literature search for relevant publications, followed by manual search of additional citations from extracted articles. The initial search yielded 44 publications; after excluding case reports, reviews, narrowly focused articles, and duplicate reports, there remained 29 articles, which are the corpus of this review. With one exception, all studies reported higher rates of H. pylori infection in HIV-negative subjects. Five studies also examined the CD4 lymphocyte counts and found an inverse correlation between the degree of immunosuppression and the prevalence of active H. pylori infection. Current evidence suggests that it is likely that H. pylori needs a functional immune system to successfully and persistently colonize the human gastric mucosa. © 2014 John Wiley & Sons Ltd.
Xie, Chuan; Lu, Nong-Hua
Helicobacter pylori (H. pylori) infection has been associated with gastric disorders. The situation of H. pylori infection in China-where a high prevalence of H. pylori infection, a high incidence of gastric cancer, and widespread resistance to clarithromycin, metronidazole, and levofloxacin exist-is quite different from that in Western countries. In order for Chinese clinicians to better manage H. pylori infection, a Chinese Study Group on H. pylori published four consensus reports regarding the management of H. pylori infection in China between 1999 and 2012. The eradication rate with standard triple therapy was <80% in most areas of China. Bismuth is available in China, and bismuth-containing quadruple therapy has been shown to produce a high eradication rate; thus, bismuth quadruple therapy could be recommended both as an initial and as a rescue therapy in China. There is no advantage of sequential therapy over triple therapy in Chinese patients, but the efficacy of concomitant therapy must be studied further. This review introduces the epidemiology, diagnosis, indicators, and therapies for the eradication of H. pylori in China in recent years. © 2014 John Wiley & Sons Ltd.
Coelho, Luiz Gonzaga Vaz; Zaterka, Schlioma
Significant progress has been obtained since the First Brazilian Consensus Conference on H. pylori Infection held in 1995, in Belo Horizonte, MG, and justify a second meeting to establish updated guidelines on the current management of H. pylori infection. The Second Brazilian Consensus Conference on H. pylori Infection was organized by the Brazilian Federation of Gastroenterology and Brazilian Nucleus for the Study of Helicobacter and took place on June, 19-20, 2004 in São Paulo, SP. Thirty six delegates coming from 15 different Brazilian states including gastroenterologists, pathologists, microbiologists and pediatricians undertook the meeting. The participants were allocated in one the five main topics of the meeting: H. pylori and dyspepsia, H. pylori and NSAIDs, H. pylori and gastroesophageal reflux disease, H. pylori treatment, and H. pylori retreatment. Seventy per cent and more votes were considered as acceptance for the final statement. The results were presented during a special session on the VI Brazilian Week of Digestive System, in Recife, PE (October 2004), and this publication represents the summary of the main recommendations and conclusions emerged from the meeting.
Lee, Jin-Uk; Kim, Okjin
AIM: To investigate maternal H pylori infection status to determine the potential of maternal transmission. METHODS: In the present study, we examined these issues in an experimental murine model, which is a Mongolian gerbil model that has been reported as an optimal laboratory animal model to study H pylori. Pregnant Mongolian gerbils, infected experimentally with H pylori, were divided into as four groups. Following the experimental design, the stomachs of the mother and litters were isolated and assessed for transmission of H pylori at the prenatal period, parturition day, 1-wk old and 3-wk old respectively. Bacterial culture and polymerase chain reaction (PCR) were used to examine the presence of transmitted H pylori. RESULTS: All litters showed no transmission of H pylori during pregnancy and at parturition day. However, they revealed 33.3% and 69.6% at 1-wk and 3-wk of age respectively by PCR. CONCLUSION: These results suggested that vertical infection during the prenatal period or delivery procedure is unlikely as a route of mother-to-child H pylori infection. It may be that H pylori is acquired through breast-feeding, contaminated saliva and fecal-oral transmission during co-habitation. PMID:17007019
Anand, Pradeep S.; Kamath, Kavitha P.; Patil, Shankargouda; Preethanath, R. S.; Anil, Sukumaran
Background. Several studies were reported on the prevalence, and relationship between the existence of Helicobacter pylori (H. pylori) in oral cavity and in stomach of patients. The purpose of this study was to systematically review the existing literature on the presence of H. pylori in the oral cavity and its link to gastric infection, the existence of coinfection, and the impact of anti-H. pylori therapy on the dental plaque and vice versa. Method. Two authors independently searched the Medline, EMBASE, Cochrane Library, Web of Science, Google Scholar, and Scopus databases for relevant studies. The articles were analyzed critically and all qualified studies were included. The search was carried out by using a combined text and the MeSH search strategies: using the key words Helicobacter, Helicobacter pylori, and H. pylori in combination with dental plaque, periodontitis, and oral hygiene. Results. The data was presented in 8 tables and each topic separately discussed. Conclusion. Based on the systematic review of the available literature on H. pylori infection and its presence in the oral cavity, it can be concluded that dental plaque can act as a reservoir, and proper oral hygiene maintenance is essential to prevent reinfection. Due to the diversified methods and population groups involved in the available literature, no concrete evidence can be laid down. Further studies are necessary to establish the role of H. pylori in the oral cavity and its eradication on preventing the gastroduodenal infection. PMID:24701355
Brown, Joseph C; Huang, Guohui; Haley-Zitlin, Vivian; Jiang, Xiuping
Anti-Helicobacter pylori activities were determined by agar dilution, confocal laser scanning microscopy, and cell proliferation assays following treatment with various grape extracts. Muscadine grape skin possessed the strongest activity, followed by grape synergy (skin and seed) and seed, suggesting that higher phenolic levels do not necessarily determine overall anti-H. pylori efficacy.
Helicobacter pylori and Aeromonas hydrophila are contaminants listed on the USEPA's 1998 Contaminant Candidate List (CCL).The sensitivity of H. pylori to chlorine and of Aeromonas spp. to inactivation by free chlorine, chloramine and ultraviolet (UV) was examined. Selective and...
A few reports have been written stating that H. pylori can be found in waters. However, detection and identification of H. pylori from water samples remains a very difficult task. One method that seems to work successfully is immunomagnetic capture. Water samples were concentr...
Ng, Chow Goon; Loke, Mun Fai; Goh, Khean Lee; Vadivelu, Jamuna; Ho, Bow
To date, the exact route and mode of transmission of Helicobacter pylori remains elusive. The detection of H. pylori in food using molecular approaches has led us to postulate that the gastric pathogen may survive in the extragastric environment for an extended period. In this study, we show that H. pylori prolongs its survival by forming biofilm and micro-colonies on vegetables. The biofilm forming capability of H. pylori is both strain and vegetable dependent. H. pylori strains were classified into high and low biofilm formers based on their highest relative biofilm units (BU). High biofilm formers survived longer on vegetables compared to low biofilm formers. The bacteria survived better on cabbage compared to other vegetables tested. In addition, images captured on scanning electron and confocal laser scanning microscopes revealed that the bacteria were able to form biofilm and reside as micro-colonies on vegetable surfaces, strengthening the notion of possible survival of H. pylori on vegetables for an extended period of time. Taken together, the ability of H. pylori to form biofilm on vegetables (a common food source for human) potentially plays an important role in its survival, serving as a mode of transmission of H. pylori in the extragastric environment. Copyright Â© 2016 Elsevier Ltd. All rights reserved.
Sonnenberg, Amnon; Genta, Robert M
Inflammatory bowel disease is known to be inversely associated with Helicobacter pylori infection of the upper gastrointestinal tract. We hypothesized that a similar inverse association also applied to microscopic colitis. The associations between microscopic colitis and presence of H. pylori-positive chronic active gastritis (CAG), H. pylori-negative CAG, intestinal metaplasia, or gastric atrophy were expressed as odds ratios with their 95% confidence intervals. Multivariate logistic regression analyses were used to adjust these associations for sex, age, percentage residents per ZIP code with white, black, Hispanic, or Asian ethnicity, percentage with college education, average housing values, annual income, and population size of individual ZIP codes. H. pylori-positive CAG was less common among patients with than without microscopic colitis (odds ratio = 0.61; 95% confidence interval, 0.52-0.70). Intestinal metaplasia also occurred less frequently among patients with than without microscopic colitis (0.75, 0.65-0.86). These inverse associations remained unaffected by adjustments for parameters of ethnicity and socioeconomic status. In contradistinction with H. pylori-positive CAG, H. pylori-negative CAG was more common in patients with than without microscopic colitis (1.54, 1.17-1.97). H. pylori infection and microscopic colitis are inversely associated. This observation is consistent with similar inverse associations found between H. pylori and inflammatory bowel disease. These relationships may provide clues about the yet unknown etiology of microscopic colitis.
Kiesslich, Ralf; Goetz, Martin; Burg, Juergen; Stolte, Manfred; Siegel, Ekkehard; Maeurer, Markus J; Thomas, Steven; Strand, Dennis; Galle, Peter R; Neurath, Markus F
Confocal laser endomicroscopy enables subsurface microscopic imaging of living tissue during ongoing endoscopy. This case report describes the in vivo detection of Helicobacter pylori by endomicroscopy. Endomicroscopy (Pentax, Tokyo, EC-3870CIFK) was performed by using two different contrast stains: Topical Acriflavine in addition to intravenously applied fluorescein netted the surface and allowed identification of focal accumulation of Helicobacter pylori at the surface and in deeper layer of the gastric epithelium. Biopsies were performed at the antrum and corpus for urease testing and histology. In addition, biopsies were cultured for Helicobacter pylori. Cultured bacteria were re-assessed ex vivo using confocal microscopy with and without acriflavine staining. Helicobacter pylori infection could be detected in a 70-year-old male by endomicroscopy. Accumulated, as well as single bacteria, could be observed and the distinct shape and flagella of Helicobacter pylori could be identified. Helicobacter pylori infection was proved by histology. Furthermore, ex vivo examination of cultures proved the presence of Helicobacter pylori and the active uptake of acriflavine into the bacteria. Endomicroscopy is a new diagnostic approach, which enables the immediate diagnosis of Helicobacter pylori in vivo during standard video endoscopy.
SHIOTA, Seiji; SUZUKI, Rumiko; YAMAOKA, Yoshio
Helicobacter pylori (H. pylori) infection is linked to various gastroduodenal diseases; however, only a small fraction of these patients develop associated diseases. Despite the high prevalence of H. pylori infection in Africa and South Asia, the incidence of gastric cancer in these areas is much lower than those in other countries. The incidence of gastric cancer tends to decrease from north to south in East Asia. Such geographic differences in the pathology can be explained, at least in part, by the presence of different types of H. pylori virulence factors in addition to the host and environmental factors. Virulence factors of H. pylori, such as cagA, vacA, dupA, iceA, oipA and babA, have been demonstrated to be predictors of severe clinical outcomes. Interestingly, meta-analysis showed that CagA seropositivity was associated with gastric cancer compared with gastritis even in East Asian countries where almost of the strains possessing cagA. Meta-analysis also confirmed the significance of vacA, dupA and iceA. However, there remains the possibility that additional important pathogenic genes can be existed because H. pylori consists of approximately 1 600 genes. Despite advances in our understanding of the development of H. pylori-related diseases, further work is required to clarify the roles of H. pylori virulence factors. PMID:23452293
Adler, Isabel; Muiño, Andrea; Aguas, Silvia; Harada, Laura; Diaz, Mariana; Lence, Adriana; Labbrozzi, Mario; Muiño, Juan Manuel; Elsner, Boris; Avagnina, Alejandra; Denninghoff, Valeria
Helicobacter pylori (H. pylori) has been found in the oral cavity and stomach, and its infection is one of the most frequent worldwide. We reviewed the literature and conducted a Topic Highlight, which identified studies reporting an association between H. pylori-infection in the oral cavity and H. pylori-positive stomach bacterium. This work was designed to determine whether H. pylori is the etiologic agent in periodontal disease, recurrent aphthous stomatitis (RAS), squamous cell carcinoma, burning and halitosis. Record selection focused on the highest quality studies and meta-analyses. We selected 48 articles reporting on the association between saliva and plaque and H. pylori-infection. In order to assess periodontal disease data, we included 12 clinical trials and 1 meta-analysis. We evaluated 13 published articles that addressed the potential association with RAS, and 6 with squamous cell carcinoma. Fourteen publications focused on our questions on burning and halitosis. There is a close relation between H. pylori infection in the oral cavity and the stomach. The mouth is the first extra-gastric reservoir. Regarding the role of H. pylori in the etiology of squamous cell carcinoma, no evidence is still available. PMID:25110422
Carbone, M; Fera, M T; Cecchetti, V; Tabarrini, O; Losi, E; Cusumano, V; Teti, G
Compounds belonging to a new class of quinolones in which the fundamental C-6 fluorine atom was replaced were evaluated for in vitro antibacterial activity against 32 Helicobacter pylori strains. Since these substitutions resulted in higher inhibitory activities, these new desfluoroquinolones may be useful in eradicating H. pylori infections. PMID:9420062
Velapatiño, Billie; Balqui, Jacqueline; Gilman, Robert H; Bussalleu, Alejandro; Quino, Willi; Finger, S Alison; Santivañez, Livia; Herrera, Phabiola; Piscoya, Alejandro; Valdivia, Jose; Cok, Jaime; Berg, Douglas E
The method of recovering Helicobacter pylori DNA or viable cells absorbed on a string that a person has swallowed and that is retrieved an hour later (string test) should be a useful alternative to traditional analysis of cells or DNA obtained by endoscopy, which is invasive, uncomfortable, relatively costly, and ill-suited for community-based and pediatric studies. Here we assayed the sensitivity and validity of the string test versus conventional endoscopic biopsy for detecting and analyzing H. pylori infection. Forty-four people with gastric complaints were studied using both H. pylori culture and urease gene (ureB) PCR. H. pylori organisms cultured from strings and biopsy specimens from the same patients were fingerprinted by the randomly amplified polymorphic DNA (RAPD) method. Biopsy sections were also hematoxylin and eosin and silver stained for H. pylori detection. H. pylori was cultured from 80% of strings and detected by PCR from 91% of strings from participants whose biopsies had been H. pylori positive by culture, PCR, and/or histology. Strains recovered from strings and biopsy specimens yielded identical or closely related RAPD profiles in each of the 24 cases tested. We conclude that the string test is a useful method for H. pylori recovery and analysis when relatively noninvasive procedures are needed.
Shiota, Seiji; Yamaoka, Yoshio
The eradication of Helicobacter pylori not only heals peptic ulcers but also prevents their recurrence and reduces the risk of development of gastric cancer and other H. pylori-associated disorders. H. pylori eradication heals gastritis and may prevent the spread of infection, reducing the future costs required for the treatment of subsequent H. pylori-associated diseases. There are various guidelines for the management of H. pylori infection worldwide, such as the guidelines of the American College of Gastroenterology, Maastricht IV, the Second Asia-Pacific Consensus Conference, and Japan. The Japanese health insurance system approved H. pylori eradication therapy for H. pylori-related chronic gastritis in 2013. Triple therapy regimens comprising 1 proton pump inhibitor and 2 antimicrobial agents such as amoxicillin, clarithromycin, metronidazole, levofloxacin, or tetracycline have been widely used to eradicate this bacterium. The rate of successful eradication has declined owing to the increased rate of drug resistance stemming from the wide usage of antibiotics. This issue is of particular relevance with regard to clarithromycin. In worldwide, clarithromycin-based triple therapy should be abandoned, as it is no longer effective. Quadruple therapy and sequential therapy are reasonable alternatives for initial therapy. First-line treatment should be recommended on the basis of an understanding of the local prevalence of H. pylori antimicrobial resistance.
Goldman, Cinthia G; Mitchell, Hazel M
Over the last 12 months, new insights into the association of non-Helicobacter pylori Helicobacters with a range of human diseases in children and adults, including hepatobiliary disease, Crohn's disease, sepsis, and gastric disease were published. Studies investigating the presence of non-H. pylori Helicobacters in domestic animals reinforce previous findings that cats and dogs harbor gastric Helicobacter species and thus may be an important source of these organisms in humans. The confounding effect of enterohepatic Helicobacters on the outcome of biomedical research was investigated in several studies and led to recommendations that animals should be screened prior to performing experiments. A number of important and novel investigations regarding pathogenic mechanisms and immune responses to enterohepatic Helicobacters were conducted. Genomic advances in non-H. pylori Helicobacters included description of the complete genome of Helicobacter canadensis, delineation of two Helicobacter bilis genomospecies, and identification of a novel cis-regulatory RNA. New insights concerning growth conditions, biochemical characterization, and the effect of certain dietary compounds on Helicobacter spp. have also been reported. © 2010 Blackwell Publishing Ltd.
Recurrence of H pylori after eradication is rare in developed countries and more frequent in developing countries. Recrudescence (recolonization of the same strain within 12 mo after eradication) rather than reinfection (colonization with a new strain, more than 12 mo after eradication) is considered to be responsible for most of the cases. This observation was confirmed only in developed countries, while in developing countries a recent meta-analysis demonstrated a high rate of reinfection. The proportion of H pylori annual recurrence was 2.67% and 13.00% in developed and developing countries, respectively. Nested meta-analysis (only cases with a longer follow-up and a negative 13CUBT a year after eradication) revealed annual recurrence rate of 1.45% [relative risk (RR), 0.54] and 12.00% (RR, 0.92) in developed and developing countries, respectively. These findings support the notion that in developed countries many cases of recurrence are due to recrudescence within the first year after eradication, with a 46% drop in the recurrence rate after the first year post eradication, while in developing countries reinfection is more pronounced, and continue at the same rate since eradication. A different approach for follow-up after H pylori eradication is probably needed in patients of developing countries, since reinfection is highly prevalent. PMID:18330934
Ayala, Guadalupe; Escobedo-Hinojosa, Wendy Itzel; de la Cruz-Herrera, Carlos Felipe; Romero, Irma
Helicobacter pylori (H. pylori) is a successful pathogen that can persist in the stomach of an infected person for their entire life. It provokes chronic gastric inflammation that leads to the development of serious gastric diseases such as peptic ulcers, gastric cancer and Mucosa associated lymphoid tissue lymphoma. It is known that these ailments can be avoided if the infection by the bacteria can be prevented or eradicated. Currently, numerous antibiotic-based therapies are available. However, these therapies have several inherent problems, including the appearance of resistance to the antibiotics used and associated adverse effects, the risk of re-infection and the high cost of antibiotic therapy. The delay in developing a vaccine to prevent or eradicate the infection has furthered research into new therapeutic approaches. This review summarises the most relevant recent studies on vaccine development and new treatments using natural resources such as plants, probiotics and nutraceuticals. In addition, novel alternatives based on microorganisms, peptides, polysaccharides, and intragastric violet light irradiation are presented. Alternative therapies have not been effective in eradicating the bacteria but have been shown to maintain low bacterial levels. Nevertheless, some of them are useful in preventing the adverse effects of antibiotics, modulating the immune response, gastroprotection, and the general promotion of health. Therefore, those agents can be used as adjuvants of allopathic anti-H. pylori eradication therapy.
O'Connor, Anthony; Fischbach, Wolfgang; Gisbert, Javier P; O'Morain, Colm
Many interesting articles have been published from different parts of the world over the last year assessing various issues around Helicobacter pylori eradication therapy. This article will address the published literature over the last year pertaining to the topic of treatment of H. pylori infection. The main themes that emerge are assessing the efficacy of standard triple therapy, as well as exploring new first-line treatments, mainly optimized nonbismuth-containing and bismuth-containing quadruple therapies with some promising data also emerging on dual therapy. There was also considerable progress in investigating antibiotic resistance rates with much more data emerging from varied parts of the world compared to recent years. Advances in the use of adjunctive therapies, especially probiotic therapies have also been made. Undoubtedly, the eradication of H. pylori remains a worthwhile goal to alleviate the burden of diseases caused by the complications of this infection, including dyspepsia, peptic ulcer disease, and gastric cancer. © 2016 John Wiley & Sons Ltd.
Ayala, Guadalupe; Escobedo-Hinojosa, Wendy Itzel; de la Cruz-Herrera, Carlos Felipe; Romero, Irma
Helicobacter pylori (H. pylori) is a successful pathogen that can persist in the stomach of an infected person for their entire life. It provokes chronic gastric inflammation that leads to the development of serious gastric diseases such as peptic ulcers, gastric cancer and Mucosa associated lymphoid tissue lymphoma. It is known that these ailments can be avoided if the infection by the bacteria can be prevented or eradicated. Currently, numerous antibiotic-based therapies are available. However, these therapies have several inherent problems, including the appearance of resistance to the antibiotics used and associated adverse effects, the risk of re-infection and the high cost of antibiotic therapy. The delay in developing a vaccine to prevent or eradicate the infection has furthered research into new therapeutic approaches. This review summarises the most relevant recent studies on vaccine development and new treatments using natural resources such as plants, probiotics and nutraceuticals. In addition, novel alternatives based on microorganisms, peptides, polysaccharides, and intragastric violet light irradiation are presented. Alternative therapies have not been effective in eradicating the bacteria but have been shown to maintain low bacterial levels. Nevertheless, some of them are useful in preventing the adverse effects of antibiotics, modulating the immune response, gastroprotection, and the general promotion of health. Therefore, those agents can be used as adjuvants of allopathic anti-H. pylori eradication therapy. PMID:24587621
Minkara, Mona S; Ucisik, Melek N; Weaver, Michael N; Merz, Kenneth M
Helicobacter pylori have been implicated in an array of gastrointestinal disorders including, but not limited to, gastric and duodenal ulcers and adenocarcinoma. This bacterium utilizes an enzyme, urease, to produce copious amounts of ammonia through urea hydrolysis in order to survive the harsh acidic conditions of the stomach. Molecular dynamics (MD) studies on the H. pylori urease enzyme have been employed in order to study structural features of this enzyme that may shed light on the hydrolysis mechanism. A total of 400 ns of MD simulation time were collected and analyzed in this study. A wide-open flap state previously observed in MD simulations on Klebsiella aerogenes [Roberts et al. J. Am. Chem. Soc.2012, 134, 9934] urease has been identified in the H. pylori enzyme that has yet to be experimentally observed. Critical distances between residues on the flap, contact points in the closed state, and the separation between the active site Ni(2+) ions and the critical histidine α322 residue were used to characterize flap motion. An additional flap in the active site was elaborated upon that we postulate may serve as an exit conduit for hydrolysis products. Finally we discuss the internal hollow cavity and present analysis of the distribution of sodium ions over the course of the simulation.
Kim, Sung Bum; Lee, Si Hyung; Bae, Seung Il; Jeong, Yo Han; Sohn, Se Hoon; Kim, Kyeong Ok; Jang, Byung Ik; Kim, Tae Nyeun
AIM To investigate the effect of Helicobacter pylori (H. pylori) status test and H. pylori eradication on the occurrence of metachronous gastric cancer (MGC) after endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) and risk factors of MGC. METHODS The authors retrospectively reviewed the medical records of 433 patients (441 lesions) who underwent ESD for EGC from January 2005 to January 2015 in Yeungnam University Hospital. Patients were categorized into two groups; the H. pylori tested group (n = 257) and the H. pylori non-tested group (n = 176) based on performance of H. pylori status test after ESD of EGC. The H. pylori tested group was further categorized into three subgroups based on H. pylori status; the H. pylori-eradicated subgroup (n = 120), the H. pylori-persistent subgroup (n = 42), and the H. pylori-negative subgroup (n = 95). Incidences of MGC and risk factors of MGC were identified. RESULTS Median follow-up duration after ESD was 30.00 mo (range, 6-107 mo). Total 15 patients developed MGC during follow-up. MGC developed in 11 patients of the H. pylori tested group (7 in the H. pylori-negative subgroup, 3 in the H. pylori-eradicated subgroup, and 1 in the H. pylori-persistent subgroup) and 4 patients of the H. pylori non-tested group (P > 0.05). The risk factors of MGC were endoscopic mucosal atrophy in the H. pylori tested group and intestinal metaplasia in all patients. CONCLUSION H. pylori eradication and H. pylori status test seems to have no preventive effect on the development of MGC after ESD for EGC. The risk factors of MGC development were endoscopic mucosal atrophy in the H. pylori tested group alone and intestinal metaplasia in all patients. PMID:27956803
Tiwari, Shridhar; Ghoshal, Ujjala; Ghoshal, Uday C; Dhingra, Sadhna; Pandey, Rakesh; Singh, Manisha; Ayyagari, Archana; Naik, Sita
Despite a possible role of Helicobacter pylori in gastric carcinoma (GC), its pathogenesis is not clear. There is scanty data on apoptosis in GC in relation to H. pylori and CagA antibody. Therefore, we studied gastric epithelial apoptosis in GC and non-ulcer dyspepsia (NUD) with or without H. pylori infection, and the degree of apoptosis in relation to CagA antibody status. 20 patients each with GC and NUD were investigated for H. pylori using rapid urease test (RUT), IgG anti-H. pylori and anti-CagA antibodies, histology of endoscopically normal-looking mucosa for H. pylori, intestinal metaplasia (IM), and apoptosis using TUNEL assay. Positivity to one tissue-based (RUT or histology) and one serology based (anti-H. pylori or CagA IgG) test was taken as diagnostic of active H. pylori infection, and negative result in both tissue-based tests suggested its absence. Patients with GC more often had anti-H. pylori IgG (16 of 20 vs. 8 of 20; p=0.02) and a trend towards higher apoptotic index (AI) (48.6 [19.2 to 71.7] vs. 41.4 [11.7 to 63.6]; p=0.06) than NUD. AI was higher in GC (66.7 [57.5 to 71.7] vs. 32.6 [19.2 to 39.8]; p<0.0001) and NUD (58.6 [50.7 to 63.6] vs. 24.4 [11.7 to 32.2]; p<0.0001) infected with H. pylori than in those without infection. AI was also higher in GC than in NUD with H. pylori infection (66.7 [57.5 to 71.7] vs. 58.6 [50.7 to 63.6]; p=0.01). Four of the 20 patients with GC and none with NUD had IM (p=ns). There was no difference in AI in relation to CagA antibody. AI positively correlated with patients' age in presence of H. pylori infection (correlation coefficient=0.5, p=0.03) but not in its absence. Exaggerated apoptosis may play a role in H. pylori-mediated gastric diseases including carcinogenesis. AI increases with aging in patients infected with H. pylori.
Missall, Tricia A; Pruden, Samuel; Nelson, Christine; Fohn, Laurel; Vidal, Claudia I; Hurley, M Yadira
A 23-year-old Chinese man presented with a 3-year history of a pruritic eruption. On examination, pink urticarial papules associated with hyperpigmented reticulated patches were noted on his neck, back, and upper chest. Histopathology revealed vacuolar interface dermatitis and numerous gram-negative rods within a dilated hair follicle. The organisms were reactive with anti-Helicobacter pylori immunohistochemisty. The histologic findings and clinical presentation support the diagnosis of prurigo pigmentosa. Additional testing demonstrated a positive urease breath test and serum H. pylori IgG antibodies. The patient was referred to gastroenterology and treated with appropriate antibiotics. After treatment, esophagogastroduodenoscopy revealed chronic gastritis without evidence of H. pylori infection and his skin showed reticulated hyperpigmented patches without evidence of active inflammatory papules. Although previous reports have associated prurigo pigmentosa to H. Pylori gastritis, this is the first report of H. pylori organisms identified in a skin biopsy of prurigo pigmentosa.
Bayerdörffer, E; Miehlke, S; Mannes, G A
Combined therapy with the proton pump inhibitor omeprazole and amoxicillin has become an important alternative in the treatment of ulcer disease associated with Helicobacter pylori infection. Due to the high efficacy in eradicating H.pylori, missing resistance of H.pylori against amoxicillin and high tolerability and digestibility this regimen may be recommended for widespread routine use. In a randomized, double-blind multicenter trial an H.pylori eradication rate of over 90% has been achieved for the first time by dual therapy using a daily omeprazole dose of 120 mg (3x40 mg) in combination with 3 x 750 mg amoxicillin for 14 days, which is comparable with classical triple therapy containing bismuth and two antibiotics. On the basis of an "intention-to-treat-analysis" dual therapy of omeprazole 3x40 mg + 3x750 mg amoxicillin is considered at present to be the most effective regimen for the treatment of H.pylori-associated diseases.
Tsukamoto, Tetsuya; Nakagawa, Mitsuru; Kiriyama, Yuka; Toyoda, Takeshi; Cao, Xueyuan
Although its prevalence is declining, gastric cancer remains a significant public health issue. The bacterium Helicobacter pylori is known to colonize the human stomach and induce chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Results using a Mongolian gerbil model revealed that H. pylori infection increased the incidence of carcinogen-induced adenocarcinoma, whereas curative treatment of H. pylori significantly lowered cancer incidence. Furthermore, some epidemiological studies have shown that eradication of H. pylori reduces the development of metachronous cancer in humans. However, other reports have warned that human cases of atrophic metaplastic gastritis are already at risk for gastric cancer development, even after eradication of these bacteria. In this article, we discuss the effectiveness of H. pylori eradication and the morphological changes that occur in gastric dysplasia/cancer lesions. We further assess the control of gastric cancer using various chemopreventive agents. PMID:28771198
Leonard, M B; Neithercut, W D; Gillen, D; McColl, K E
AIM: To determine whether Helicobacter pylori releases cysteamine into gastric juice as cysteamine is known to be ulcerogenic. METHODS: Samples of fasting gastric juice were collected from 22 individuals (four women); 10 subjects were H pylori negative. The presence of infection was confirmed by examination and culture of gastric biopsies. Cysteamine in gastric juice was measured by reversed phase gradient high performance liquid chromatography with a detection limit of 10 mumol/l. RESULTS: Cysteamine was not detected in any of the gastric juice samples or in extracts of cultured H pylori. CONCLUSIONS: If H pylori produces cysteamine then the amounts produced are insignificant and are unlikely to explain the association between H pylori infection and the development of duodenal ulcer disease. PMID:9389979
Czajkowski, A; Piotrowski, J; Yotsumoto, F; Slomiany, A; Slomiany, B L
Sulglycotide, a potent antiulcer agent derived from duodenal mucus glycopeptide through sulfation of the carbohydrate moieties, was evaluated with respect to its ability to interfere with H. pylori mucosal attachment. H. pylori cells were incubated with sulglycotide or human gastric mucin and then examined for their inhibitory capacity of H. pylori attachment to erythrocytes. Titration data revealed that the mucin inhibitory activity was confined to its sulfomucin fraction, the titer of which was found to be 16-fold higher than that of intact mucin. The data with sulglycotide showed that the inhibitory titer of this agent against H. pylori attachment was at least 30-fold higher than that of the sulfated gastric mucin fraction. The results point towards the involvement of sulfomucins in the protection of gastric mucosa from H. pylori colonization and demonstrate that sulglycotide, because of structural similarities, is ideally suited to augment the inherent mucosal defenses against this pathogen.
Milani, Morteza; Sharifi, Yaeghob; Rahmati-Yamchi, Mohammad; Somi, Mohammad H; Akbarzadeh, Abolfazl
Helicobacter pylori infection is very common worldwide and is an important cause of gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma, and gastric adenocarcinoma. Since the eradication requires treatment with multidrug regimens, prevention of primary infection by a suitable vaccine is attractive. Developing vaccines on the spot when and where an infection is breaking out might be possible, thanks to engineered nanoparticles. In this review, the nature of the host immune response to H. pylori infection is considered. We explain recent candidate vaccines and prophylactic or therapeutic immunization strategies for use against H. pylori. We also describe identification of different types of immune responses that may be related to protection against H. pylori infection. Thus, it seems that there is still a strong need to clarify the main protective immune response against H. pylori.
Wermeille, J; Zelger, G; Cunningham, M
The eradication of Helicobacter pylori is at present widely recognized as the adequate therapeutic approach for gastric and duodenal ulcers in infected patients. In those with dyspepsia but no ulcer as well as in those with type B chronic gastritis, eradication remains controversial. It is difficult to have a clear opinion on the advantages and disadvantages of the numerous existing therapies. Therefore, a systematic review of published treatments has been made by the authors. Ideally, the eradication treatment of H. pylori should have the following advantages: 1. eradication superior to 90%, 2. simplicity, 3. short duration, 4. safety, 5. low cost, 6. reproducibility of results. Dual therapies (2 antibiotics or a proton pump inhibitor in combination with an antibiotic) rarely allow an eradication greater than 90% and the results have poor reproducibility. Consequently, they do not represent an ideal anti-H. pylori treatment. Triple therapies come closer to the requirements for an ideal treatment, with eradication rates generally close to 90%, varying little between studies and the countries in which they were performed. The triple therapy bismuth-imidazole-tetracycline (or amoxicillin) still represents for many authors the standard reference therapy. It has the advantage of low cost, high efficacy and widespread use. It is the therapy that has been the most studied. However, the increasing emergence of strains resistant to imidazoles, the complexity of the treatment (10 to 12 tablets per day), the numerous adverse effects and the lack of availability of bismuth salts in certain countries has led to the elaboration of therapeutic schemes combining an antisecretory drug with 2 antibiotics. Among these, the combination PPI-clarithromycine-imidazole during 7 days represents the most studied triple therapy of short duration for some authors, it already represents a new standard. However, the efficacy of this therapy seems dependent on the sensitivity of the bacteria to
Gisbert, Javier P
Below is a summary of the main conclusions that came from reports presented at this year's Digestive Disease Week (2014) relating to Helicobacter pylori infection. Despite the undeniable decline of the infection's frequency, in the near future, developed countries--or at least some sub-populations--will continue to have a significant prevalence of the infection. Clarithromycin, metronidazole and quinolone resistance rates are considerably high in most countries and these rates are on the rise. The eradication of H. pylori improves symptoms of functional dyspepsia, although only in a minority of patients; adding antidepressants to eradication therapy could improve long-term response. In patients who were admitted with gastrointestinal bleeding from peptic ulcers, it is necessary to thoroughly study the presence of H. pylori infection and administer eradication therapy as early as possible. Eradication of H. pylori in patients undergoing endoscopic resection of early-stage gastric cancer reduces incidence of metachronous tumors. We have some diagnostic innovations, such as carrying out various techniques--a rapid urease test, culture or PCR--based on gastric samples obtained by scraping the mucosa. The effectiveness of conventional triple therapy is clearly insufficient and continues to decline. The superiority of sequential therapy over conventional triple therapies has not been definitively established. Concomitant therapy is simpler and more effective than sequential therapy. Optimized concomitant therapy (with high doses of proton-pump inhibitors [PPI] and over 14 days) is highly effective, more so than standard concomitant therapy. For patients who are allergic to penicillin, 2 treatment options were essentially described: PPI-clarithromycin-metronidazole (clarithromycin-sensitive strains) and quadruple therapy with bismuth (when the bacterial sensitivity is unknown). If conventional triple therapy fails, second-line therapy with levofloxacin is effective and is
Gião, M S; Azevedo, N F; Wilks, S A; Vieira, M J; Keevil, C W
Although the route of transmission of Helicobacter pylori remains unknown, drinking water has been considered a possible transmission vector. It has been shown previously that, in water, biofilms are a protective niche for several pathogens, protecting them from stressful conditions, such as low carbon concentration, shear stress, and less-than-optimal temperatures. In this work, the influence of these three parameters on the persistence and cultivability of H. pylori in drinking-water biofilms was studied. Autochthonous biofilm consortia were formed in a two-stage chemostat system and then inoculated with the pathogen. Total numbers of H. pylori cells were determined by microscopy using a specific H. pylori 16S rRNA peptide nucleic acid probe, whereas cultivable cells were assessed by standard plating onto selective H. pylori medium. Cultivable H. pylori could not be detected at any time point, but the ability of H. pylori cells to incorporate, undergo morphological transformations, persist, and even agglomerate in biofilms for at least 31 days without a noticeable decrease in the total cell number (on average, the concentration was between 1.54 x 10(6) and 2.25 x 10(6) cells cm(-2)) or in the intracellular rRNA content may indicate that the loss of cultivability was due to entry into a viable but noncultivable state. Unlike previous results obtained for pure-culture H. pylori biofilms, shear stress did not negatively influence the numbers of H. pylori cells attached, suggesting that the autochthonous aquatic bacteria have an important role in retaining this pathogen in the sessile state, possibly by providing suitable microaerophilic environments or linking biomolecules to which the pathogen adheres. Therefore, biofilms appear to provide not only a safe haven for H. pylori but also a concentration mechanism so that subsequent sloughing releases a concentrated bolus of cells that might be infectious and that could escape routine grab sample microbiological
Khatoon, Jahanarah; Rai, Ravi Prakash; Prasad, Kashi Nath
Helicobacter pylori (H. pylori) infection is highly prevalent in human, affecting nearly half of the world’s population; however, infection remains asymptomatic in majority of population. During its co-existence with humans, H. pylori has evolved various strategies to maintain a mild gastritis and limit the immune response of host. On the other side, presence of H. pylori is also associated with increased risk for the development of various gastric pathologies including gastric cancer (GC). A complex combination of host genetics, environmental agents, and bacterial virulence factors are considered to determine the susceptibility as well as the severity of outcome in a subset of individuals. GC is one of the most common cancers and considered as the third most common cause of cancer related death worldwide. Many studies had proved H. pylori as an important risk factor in the development of non-cardia GC. Although both H. pylori infection and GC are showing decreasing trends in the developed world, they still remain a major threat to human population in the developing countries. The current review attempts to highlight recent progress in the field of research on H. pylori induced GC and aims to provide brief insight into H. pylori pathogenesis, the role of major virulence factors of H. pylori that modulates the host environment and transform the normal gastric epithelium to neoplastic one. This review also emphasizes on the mechanistic understanding of how colonization and various virulence attributes of H. pylori as well as the host innate and adaptive immune responses modulate the diverse signaling pathways that leads to different disease outcomes including GC. PMID:26909129
Toyonaga, A; Okamatsu, H; Sasaki, K; Kimura, H; Saito, T; Shimizu, S; Fukuizumi, K; Tsuruta, O; Tanikawa, K; Sata, M
We conducted an epidemiological study to investigate the relation of food intake to Helicobacter pylori (H. pylori) infection in an area endemic for H. pylori. In this study, 365 subjects, 104 men and 261 women, were randomly selected from 7,389 adult (over age 20) inhabitants of town A, Japan. The prevalence of immunoglobulin G (IgG) class antibody to H. pylori (anti-H. pylori) was 83.7% and the prevalence of anti-H. pylori increased with age significantly (P < 0.05). Subjects with anamnesis of gastritis, gastroduodenal ulcer and gastric cancer tended to have a higher anti-H. pylori positive ratio (93.5%) than those without (81.0%). But there was no relationship between anti-H. pylori prevalence and sex, blood type, smoking or drinking habits. Daily intake of foods by food groups, nutrients and the concentrations of serum ingredients were compared between 37 anti-H. pylori-positive and 40 negative subjects selected from 365 inhabitants by matching up according to sex and age. The daily intake of cereals, potatoes and starches, and milks tended to be higher in positive than negative subjects, while the daily intake of algae and tea appeared to be a little higher in negative than in positive subjects. The daily zinc intake of antibody-positive subjects was significantly higher (P < 0.05) than in antibody negative subjects. On the other hand, the daily iron intake in negative subjects was significantly higher (P < 0.05) than in positive subjects. The serum concentrations of copper, zinc, and vitamin E tended to be higher in positive than negative subjects. But there were no significant differences in serum ingredients concentrations between antibody negative and positive subjects. Our findings suggest that iron and zinc intakes may effect on H. pylori infection.
Dorer, Marion S; Talarico, Sarah; Salama, Nina R
The discovery of a bacterium, Helicobacter pylori, that is resident in the human stomach and causes chronic disease (peptic ulcer and gastric cancer) was radical on many levels. Whereas the mouth and the colon were both known to host a large number of microorganisms, collectively referred to as the microbiome, the stomach was thought to be a virtual Sahara desert for microbes because of its high acidity. We now know that H. pylori is one of many species of bacteria that live in the stomach, although H. pylori seems to dominate this community. H. pylori does not behave as a classical bacterial pathogen: disease is not solely mediated by production of toxins, although certain H. pylori genes, including those that encode exotoxins, increase the risk of disease development. Instead, disease seems to result from a complex interaction between the bacterium, the host, and the environment. Furthermore, H. pylori was the first bacterium observed to behave as a carcinogen. The innate and adaptive immune defenses of the host, combined with factors in the environment of the stomach, apparently drive a continuously high rate of genomic variation in H. pylori. Studies of this genetic diversity in strains isolated from various locations across the globe show that H. pylori has coevolved with humans throughout our history. This long association has given rise not only to disease, but also to possible protective effects, particularly with respect to diseases of the esophagus. Given this complex relationship with human health, eradication of H. pylori in nonsymptomatic individuals may not be the best course of action. The story of H. pylori teaches us to look more deeply at our resident microbiome and the complexity of its interactions, both in this complex population and within our own tissues, to gain a better understanding of health and disease.
Kim, Songhee H; Langford, Melanie L; Boucher, Jean-Luc; Testerman, Traci L; McGee, David J
AIM: To investigate the role of host and bacterial arginases in the colonization of mice by Helicobacter pylori (H. pylori). METHODS: H. pylori produces a very powerful urease that hydrolyzes urea to carbon dioxide and ammonium, which neutralizes acid. Urease is absolutely essential to H. pylori pathogenesis; therefore, the urea substrate must be in ample supply for urease to work efficiently. The urea substrate is most likely provided by arginase activity, which hydrolyzes L-arginine to L-ornithine and urea. Previous work has demonstrated that H. pylori arginase is surprisingly not required for colonization of wild-type mice. Hence, another in vivo source of the critical urea substrate must exist. We hypothesized that the urea source was provided by host arginase II, since this enzyme is expressed in the stomach, and H. pylori has previously been shown to induce the expression of murine gastric arginase II. To test this hypothesis, wild-type and arginase (rocF) mutant H. pylori strain SS1 were inoculated into arginase II knockout mice. RESULTS: Surprisingly, both the wild-type and rocF mutant bacteria still colonized arginase II knockout mice. Moreover, feeding arginase II knockout mice the host arginase inhibitor S-(2-boronoethyl)-L-cysteine (BEC), while inhibiting > 50% of the host arginase I activity in several tissues, did not block the ability of the rocF mutant H. pylori to colonize. In contrast, BEC poorly inhibited H. pylori arginase activity. CONCLUSION: The in vivo source for the essential urea utilized by H. pylori urease is neither bacterial arginase nor host arginase II; instead, either residual host arginase I or agmatinase is probably responsible. PMID:21876618
Abadi, Amin Talebi Bezmin
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
Link, Alexander; Langner, Cosima; Schirrmeister, Wiebke; Habendorf, Wiebke; Weigt, Jochen; Venerito, Marino; Tammer, Ina; Schlüter, Dirk; Schlaermann, Philipp; Meyer, Thomas F; Wex, Thomas; Malfertheiner, Peter
To evaluate the frequency of Helicobacter pylori (H. pylori) CagA antibodies in H. pylori infected subjects and to identify potential histopathological and bacterial factors related to H. pylori CagA-immune response. Systematic data to H. pylori isolates, blood samples, gastric biopsies for histological and molecular analyses were available from 99 prospectively recruited subjects. Serological profile (anti-H. pylori, anti-CagA) was correlated with H. pylori isolates (cagA, EPIYA, vacA s/m genotype), histology (Sydney classification) and mucosal interleukin-8 (IL-8) mRNA and protein expression. Selected H. pylori strains were assessed for H. pylori CagA protein expression and IL-8 induction in co-cultivation model with AGS cells. Thirty point three percent of microbiologically confirmed H. pylori infected patients were seropositive for CagA. Majority of H. pylori isolates were cagA gene positive (93.9%) with following vacA polymorphisms: 42.4% vacA s1m1, 23.2% s1m2 and 34.3% s2m2. Anti-CagA-IgG seropositivity was strongly associated with atrophic gastritis, increased mucosal inflammation according to the Sydney score, IL-8 and cagA mRNA expression. VacA s and m polymorphisms were the major determinants for positive (vacA s1m1) or negative (vacA s2m2) anti-CagA serological immune response, which also correlated with the in vitro inflammatory potential in AGS cells. In vitro co-cultivation of representative H. pylori strains with AGS cells confirmed functional CagA translocation, which showed only partial correlation with CagA seropositivity in patients, supporting vacA as major co-determinant of the immune response. Serological immune response to H. pylori cagA+ strain in H. pylori infected patients is strongly associated with vacA polymorphism, suggesting the crucial role of bacterial factors in immune and clinical phenotype of the infection.
Safaei, Hajieh Ghasemian; Rahimi, Ebrahim; Zandi, Ashkan; Rashidipour, Alireza
The prevalence of Helicobacter pylori infection, which may increase the risk of gastritis, peptic ulcers, and cancer, has increased worldwide. This number is estimated to be around 70-90% in developing countries and 25-50% in developed countries. It is possible that the bacterium can be transmitted via food and water as well as zoonotically and iatrogenically. Because of high prevalence of this infection in Iran, the aim of this study is to examine whether H. pylori infection might be transmitted from cow's milk and faeces. The existence of the H. pylori antibody and antigen was investigated in samples of serum, milk, and faeces from 92 lactating Holstein cows in Shahrekord, Iran. The H. pylori antigen and antibody were detected using ELISA and were confirmed by PCR. It was found that out of 92 serum specimens, 25 (27%) of the cows were positive for the H. pylori antibody and 67 specimens were negative. From these 25 seropositive cows, 10 (40%) faeces samples and four (16%) milk samples were antigen positive for H. pylori. Four of the antigen-positive milk specimens were also antigen positive for faeces. The existence of the UreC gene was also confirmed in positive samples of milk and faeces. There is a possibility that cow's milk is a transmission mode in H. pylori infection and faecal contamination and inappropriate management processes could transfer H. pylori to humans. The awareness of the H. pylori epidemiology and its method of distribution are necessary for public health measures and controlling the spread of this bacterium. Further investigation with a greater sample number is necessary to verify the ability of H. pylori transmission via milk consumption.
Shang, Xiaodong; Tan, Qi; Liu, Ruina; Yu, Kangying; Li, Pingzuo; Zhao, Guo-Ping
Although the medicinal mushroom Hericium erinaceus is used extensively in traditional Chinese medicine to treat chronic superficial gastritis, the underlining pharmaceutical mechanism is yet to be fully understood. In this study, minimum inhibitory concentration (MIC) values of extracts prepared from the fruiting bodies of 14 mushroom species (H. erinaceus, Ganoderma lucidum, Cordyceps militaris, Pleurotus eryngii, P. ostreatus, Agrocybe aegerita, Lentinus edodes, Agaricus brasiliensis, A. bisporus, Coprinus comatus, Grifola frondosa, Phellinus igniarius, Flammulina velutipes, and Hypsizygus marmoreus) were determined against Helicobacter pylori using laboratory strains of ATCC 43504 and SS1 as well as 9 clinical isolates via an in vitro microplate agar diffusion assay. Ethanol extracts (EEs) of 12 mushrooms inhibited the growth of H. pylori in vitro, with MIC values <3 mg/mL. EEs of H. erinaceus and G. lucidum also inhibited Staphylococcus aureus (MIC 7360;10 mg/mL) but had no effect on the growth of two Escherichia coli test strains (MIC >10 mg/mL). MIC values of ethyl acetate fractions (EAFs) of H. erinaceus against 9 clinical isolates of H. pylori ranged between 62.5 and 250 µg/mL. The bacteriostatic activity of EAFs was found to be concentration-dependant, and the half maximal inhibitory concentration and minimum bactericidal concentration values for H. pylori ATCC 43504 were 73.0 and 200 µg/mL, respectively. The direct inhibitory effect of EEs and EAFs of H. erinaceus against H. pylori could be another pharmaceutical mechanism of medicinal mushrooms-besides the immunomodulating effect of polysaccharides, suggested previously-in the treatment of H. pylori-associated gastrointestinal disorders. Further research to identify the active component(s) is currently undertaking in our laboratory.
Panpetch, Wimonrat; Spinler, Jennifer K; Versalovic, James; Tumwasorn, Somying
Interleukin (IL)-8 is the key agent for initiating an inflammatory response to infection with Helicobacter pylori. Some strains of Lactobacillus spp. are known to colonize the stomach and suppress inflammation caused by H. pylori. In this study, we characterized two gastric-derived lactobacilli, Lactobacillus salivarius (LS) strains B37 and B60, capable of inhibiting H. pylori-induced IL-8 production by gastric epithelial cells. Conditioned media from LS-B37 and LS-B60 suppressed H. pylori-induced IL-8 production and mRNA expression from AGS cells without inhibiting H. pylori growth. These conditioned media suppressed the activation of NF-κB but did not suppress c-Jun activation. IL-8 inhibitory substances in conditioned media of LS-B37 and LS-B60 are heat-stable and larger than 100 kDa in size. The inhibitory activity of LS-B37 was abolished when the conditioned medium was treated with α-amylase but still remained when treated with either proteinase K, trypsin, lipase or lysozyme. The activity of LS-B60 was abolished when the conditioned medium was treated with either amylase or proteinase K but still remained when treated with lysozyme. Treatment with lipase and trypsin also significantly affected the inhibitory activity of LS-B60 although the conditioned medium retained IL-8 suppression statistically different from media control. These results suggest that L. salivarius strains B37 and B60 produce different immunomodulatory factors capable of suppressing H. pylori-induced IL-8 production from gastric epithelial cells. Our results suggest that the large, heat-stable immunomodulatory substance(s) present in the LCM of LS-B37 is a polysaccharide, while the one(s) of LS-B60 is either complex consisting of components of polysaccharide, lipid and protein or includes multiple components such as glycoprotein and lipoprotein.
McNulty, Shannon L.; Mole, Beth M.; Dailidiene, Daiva; Segal, Issy; Ally, Reid; Mistry, Rajesh; Secka, Ousman; Adegbola, Richard A.; Thomas, Julian E.; Lenarcic, Erik M.; Peek, Richard M.; Berg, Douglas E.; Forsyth, Mark H.
Helicobacter pylori is a genetically diverse bacterial species that chronically infects human stomachs and sometimes causes severe gastroduodenal disease. Studies of polymorphic DNA sequences can suggest geographic origins of individual strains. Here, we describe a 180-bp insertion (ins180), which is just after the translation stop of a gene of unknown function, near the promoter of jhp0152-jhp0151 two-component signal transduction genes in strain J99, and absent from this site in strain 26695. This ins180 insertion was found in 9 of 9 Gambian (West African), 9 of 20 (45%) South African, and 9 of 40 (23%) Spanish strains but in only 2 of 20 (10%) North American strains and none of 20 Lithuanian, 20 Indian, and 20 Japanese strains. Four South African isolates that lacked ins180 and that belonged to an unusual outlier group contained a 480-bp insertion at this site (ins480), whereas none of 181 other strains screened contained ins480. In further tests 56% (10 of 18) of strains from African Americans but only 17% (3 of 18) of strains from Caucasian Americans carried ins180 (P < 0.05). Thus, the H. pylori strains of modern African Americans seem to retain traces of African roots, despite the multiple generations since their ancestors were taken from West Africa. Fragmentary ins180-like sequences were found at numerous sites in H. pylori genomes, always between genes. Such sequences might affect regulation of transcription and could facilitate genome rearrangement by homologous recombination. Apparent differences between African-American and Caucasian-American H. pylori gene pools may bear on our understanding of H. pylori transmission and disease outcome. PMID:15583296
McNulty, Shannon L; Mole, Beth M; Dailidiene, Daiva; Segal, Issy; Ally, Reid; Mistry, Rajesh; Secka, Ousman; Adegbola, Richard A; Thomas, Julian E; Lenarcic, Erik M; Peek, Richard M; Berg, Douglas E; Forsyth, Mark H
Helicobacter pylori is a genetically diverse bacterial species that chronically infects human stomachs and sometimes causes severe gastroduodenal disease. Studies of polymorphic DNA sequences can suggest geographic origins of individual strains. Here, we describe a 180-bp insertion (ins180), which is just after the translation stop of a gene of unknown function, near the promoter of jhp0152-jhp0151 two-component signal transduction genes in strain J99, and absent from this site in strain 26695. This ins180 insertion was found in 9 of 9 Gambian (West African), 9 of 20 (45%) South African, and 9 of 40 (23%) Spanish strains but in only 2 of 20 (10%) North American strains and none of 20 Lithuanian, 20 Indian, and 20 Japanese strains. Four South African isolates that lacked ins180 and that belonged to an unusual outlier group contained a 480-bp insertion at this site (ins480), whereas none of 181 other strains screened contained ins480. In further tests 56% (10 of 18) of strains from African Americans but only 17% (3 of 18) of strains from Caucasian Americans carried ins180 (P < 0.05). Thus, the H. pylori strains of modern African Americans seem to retain traces of African roots, despite the multiple generations since their ancestors were taken from West Africa. Fragmentary ins180-like sequences were found at numerous sites in H. pylori genomes, always between genes. Such sequences might affect regulation of transcription and could facilitate genome rearrangement by homologous recombination. Apparent differences between African-American and Caucasian-American H. pylori gene pools may bear on our understanding of H. pylori transmission and disease outcome.
Kim, Aeryun; Servetas, Stephanie L; Kang, Jieun; Kim, Jinmoon; Jang, Sungil; Choi, Yun Hui; Su, Hanfu; Jeon, Yeong-Eui; Hong, Youngmin A; Yoo, Yun-Jung; Merrell, D Scott; Cha, Jeong-Heon
The array of outer membrane proteins (OMPs) found in Helicobacter pylori provides a crucial component for persistent colonization within the gastric niche. Not only does H. pylori harbor a wide number of OMPs, but these OMPs often vary across strains; this likely contributes to immune evasion, adaptation during long term colonization, and potentially differential disease progression. Previous work from our group described OMP differences among the Bab family (babA, babB, and babC) and Hom family (homA and homB) from 80 American H. pylori clinical isolates (AH) and 80 South Korean H. pylori clinical isolates (KH). In the current study, we expanded our investigation to include the less well characterized Hom family member, HomC.Overall, we identified and genotyped three homC variants: homC (S) , homC (L) , and homC (M) , in both populations. Similar to other polymorphic genes, the KH group showed less overall diversity, with 97.5% of strains harboring homC (L) . In contrast, a more heterogeneous profile was observed in strains derived from an American population; we found nearly equal distribution of homC (S) and homC (L) . Further analysis of the AH group identified associations between homC polymorphism and bab genotype; in AH strains, there was a significant association between homC (L) and carriage of babA at locus A. Since babA is an important virulence factor for the development of severe gastric disease, these data may suggest that homC polymorphism plays a role in H. pylori pathogenesis.
Fernández de Larrea-Baz, Nerea; Pérez-Gómez, Beatriz; Michel, Angelika; Romero, Beatriz; Lope, Virginia; Pawlita, Michael; Fernández-Villa, Tania; Moreno, Victor; Martín, Vicente; Willhauck-Fleckenstein, Martina; López-Abente, Gonzalo; Castilla, Jesús; Fernández-Tardón, Guillermo; Dierssen-Sotos, Trinidad; Santibáñez, Miguel; Peiró, Rosana; Jiménez-Moleón, José Juan; Navarro, Carmen; Castaño-Vinyals, Gemma; Kogevinas, Manolis; Pollán, Marina; de Sanjosé, Silvia; Del Campo, Rosa; Waterboer, Tim; Aragonés, Nuria
Helicobacter pylori infection is one of the main risk factors for non-cardia gastric cancer. However, only a minority of infected persons develop the disease. This study aims at identifying H. pylori related serological biomarkers of risk for gastric cancer. Incident gastric cancer cases and population controls (age, sex and region frequency-matched) from the MCC-Spain multicase-control Study were included. Seroreactivities against 16H. pylori proteins were determined using multiplex serology. Infection was defined as seropositivity against≥4 proteins. Relation of serological results to non-cardia and cardia gastric cancer was assessed using multivariable mixed logistic regression and principal components analysis. Seroprevalence was 88% among 2071 controls, 95% among 202 non-cardia gastric cancer cases (OR=1.9 (95% CI: 1.0-3.6)) and 85% among 62 cardia cancer cases (OR=0.5 (95% CI: 0.3-1.1)). In infected subjects, seropositivity for UreA, HP231, NapA and Cagδ was associated with lower non-cardia gastric cancer risk, while seropositivity for CagA and VacA was associated with higher risk. Seropositivity for CagA and seronegativity for Cagδ maintained the association after additional adjustment by serostatus of significant proteins. We identified two antibody reactivity patterns: the "virulent-pattern", related to a threefold higher risk of non-cardia gastric cancer and the "non-virulent pattern", related to a 60% decreased risk (4th vs. first quartile). In our population, people seropositive for H. pylori were characterized by two patterns of antibody reactivity against H. pylori proteins: 1) Combined high seroreactivity against several proteins, associated with a lower non-cardia gastric cancer risk, and 2) High seroreactivity against CagA and VacA, associated with an increased risk. Copyright © 2017 Elsevier Ltd. All rights reserved.
Suarez, Giovanni; Romero-Gallo, Judith; Piazuelo, M. Blanca; Wang, Ge; Maier, Robert J.; Forsberg, Lennart S.; Azadi, Parastoo; Gomez, Martin A.; Correa, Pelayo; Peek, Jr., Richard M.
Helicobacter pylori is the strongest known risk factor for gastric carcinogenesis. One cancer-linked locus is the cag pathogenicity island, which translocates components of peptidoglycan (PGN) into host cells. NOD1 is an intracellular immune receptor that senses PGN from Gram-negative bacteria and responds by inducing autophagy and activating NF-κB, leading to inflammation-mediated bacterial clearance; however chronic pathogens can evade NOD1-mediated clearance by altering PGN structure. We previously demonstrated that the H. pylori cag+ strain 7.13 rapidly induces gastric cancer in Mongolian gerbils. Using 2D-DIGE and mass spectrometry, we identified a novel mutation within the gene encoding the peptidoglycan deacetylase PgdA; therefore, we sought to define the role of H. pylori PgdA in NOD1-dependent activation of NF-κB, inflammation, and cancer. Co-culture of H. pylori strain 7.13 or its pgdA$-$ isogenic mutant with AGS gastric epithelial cells or HEK293 epithelial cells expressing a NF-κB reporter revealed that pgdA inactivation significantly decreased NOD1-dependent NF-κB activation and autophagy. Infection of Mongolian gerbils with an H. pylori pgdA$-$ mutant strain led to significantly decreased levels of inflammation and malignant lesions in the stomach; however, pre-activation of NOD1 prior to bacterial challenge reciprocally suppressed inflammation and cancer in response to wild-type H. pylori. Expression of NOD1 differs in human gastric cancer specimens compared to non-cancer samples harvested from the same patients. In conclusion, these results indicate that PGN deacetylation plays an important role in modulating host inflammatory responses to H. pylori, allowing the bacteria to persist and induce carcinogenic consequences in the gastric niche.
Helicobacter pylori (H. pylori) infection is associated with a variety of upper gastrointestinal diseases, including gastric cancer. With the wide application of antibiotics in H. pylori eradication treatment, drug-resistant strains of H. pylori are increasing. H. pylori eradication treatment failure affects the outcome of a variety of diseases of the upper gastrointestinal tract. Therefore, antibiotic resistance that affects H. pylori eradication treatment is a challenging situation for clinicians. The ideal H. pylori eradication therapy should be safe, effective, simple, and economical. The eradication rate of triple antibiotic therapy is currently less than 80% in most parts of the world. Antibiotic resistance is the main reason for treatment failure, therefore the standard triple regimen is no longer suitable as a first-line treatment in most regions. H. pylori eradication treatment may fail for a number of reasons, including H. pylori strain factors, host factors, environmental factors, and inappropriate treatment.
ZHAO, WEIDONG; ZHONG, XIAOQIN; ZHUANG, XINYING; JI, HONGMEI; LI, XINXIN; LI, ANQING; WANG, RUICAI; ZHU, JIANYOU; LI, YANQING
The aim of this study was to assess the effect of Helicobactor pylori (H. pylori) infection and drug therapy on functional dyspepsia (FD) symptoms and gastrointestinal eosinophil count. In this study, 215 continuous FD patients fulfilling Rome III criteria were enrolled. The patients were divided into a H. pylori-positive group and a H. pylori-negative group. The H. pylori-positive group was divided into H. pylori-eradicated and H. pylori-uneradicated groups following H. pylori-eradication treatment, and the H. pylori-negative group was randomly divided into esomeprazole and teprenone treatment groups. The symptom scores of the esomeprazole group were significantly lower compared with those of the teprenone group at week 6 but not at baseline and week 2. Compared with the H. pylori-uneradicated group, eosinophil counts in the antrum and body were significantly reduced in the H. pylori-eradicated group at week 6. The number of gastric eosinophil clusters was significantly higher in the H. pylori-positive group than in the H. pylori-negative group. Eradication was associated with gastric eosinophil counts but did not affect duodenal eosinophil levels. Neither esomeprazole nor teprenone treatments reduced eosinophil levels in the stomach and duodenum of H. pylori-negative patients. PMID:23935715
Cravedi, Pietro; Mori, Giulia; Fischer, Frédéric; Percudani, Riccardo
By competing for the acquisition of essential nutrients, Helicobacter pylori has the unique ability to persist in the human stomach, also causing nutritional insufficiencies in the host. Although the H. pylori genome apparently encodes selenocysteine synthase (SelA, HP1513), a key pyridoxal phosphate (PLP)-dependent enzyme for the incorporation of selenium into bacterial proteins, nothing is known about the use of this essential element in protein synthesis by this pathogen. We analyzed the evolution of the complete machinery for incorporation of selenium into proteins and the selenoproteome of several H. pylori strains and related Epsilonproteobacteria. Our searches identified the presence of selenoproteins—including the previously unknown DUF466 family—in various Epsilonproteobacteria, but not in H. pylori. We found that a complete system for selenocysteine incorporation was present in the Helicobacteriaceae ancestor and has been recently lost before the split of Helicobacter acinonychis and H. pylori. Our results indicate that H. pylori, at variance with other gastric and enterohepatic Helicobacter, does not use selenocysteine in protein synthesis and does not use selenium for tRNA wobble base modification. However, selA has survived as a functional gene, having lost the domain for the binding of selenocysteine tRNA, but maintaining the ability to bind the PLP cofactor. The evolutionary modifications described for the SelA protein of H. pylori find parallels in other bacterial and archaeal species, suggesting that an alternative enzymatic function is hidden in many proteins annotated as selenocysteinyl-tRNA synthase. PMID:26342139
Zhang, Rong-Guang; Duan, Guang-Cai; Fan, Qing-Tang; Chen, Shuai-Yin
Gastric cancer (GC) is one of the most common carcinoma and the second leading cause of cancer-related deaths worldwide. Helicobacter pylori (H. pylori) infection causes a series of precancerous lesions like gastritis, atrophy, intestinal metaplasia and dysplasia, and is the strongest known risk factor for GC, as supported by epidemiological, preclinical and clinical studies. However, the mechanism of H. pylori developing gastric carcinoma has not been well defined. Among infected individuals, approximately 10% develop severe gastric lesions such as peptic ulcer disease, 1%-3% progresses to GC. The outcomes of H. pylori infection are determined by bacterial virulence, genetic polymorphism of hosts as well as environmental factors. It is important to gain further understanding of the pathogenesis of H. pylori infection for developing more effective treatments for this common but deadly malignancy. The recent findings on the bacterial virulence factors, effects of H. pylori on epithelial cells, genetic polymorphism of both the bacterium and its host, and the environmental factors for GC are discussed with focus on the role of H. pylori in gastric carcinogenesis in this review. PMID:26909232
Safavi, Maliheh; Sabourian, Reyhaneh; Foroumadi, Alireza
Helicobacter pylori (H. pylori) is an important major cause of peptic ulcer disease and gastric malignancies such as mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma worldwide. H. pylori treatment still remains a challenge, since many determinants for successful therapy are involved such as individual primary or secondary antibiotics resistance, mucosal drug concentration, patient compliance, side-effect profile and cost. While no new drug has been developed, current therapy still relies on different mixture of known antibiotics and anti-secretory agents. A standard triple therapy consisting of two antibiotics and a proton-pump inhibitor proposed as the first-line regimen. Bismuth-containing quadruple treatment, sequential treatment or a non-bismuth quadruple treatment (concomitant) are also an alternative therapy. Levofloxacin containing triple treatment are recommended as rescue treatment for infection of H. pylori after defeat of first-line therapy. The rapid acquisition of antibiotic resistance reduces the effectiveness of any regimens involving these remedies. Therefore, adding probiotic to the medications, developing anti-H. pylori photodynamic or phytomedicine therapy, and achieving a successful H. pylori vaccine may have the promising to present synergistic or additive consequence against H. pylori, because each of them exert different effects. PMID:26798626
Franceschi, Francesco; Annalisa, Tortora; Teresa, Di Rienzo; Giovanna, D’Angelo; Ianiro, Gianluca; Franco, Scaldaferri; Viviana, Gerardi; Valentina, Tesori; Riccardo, Lopetuso Loris; Antonio, Gasbarrini
Helicobacter pylori (H. pylori) is a gram-negative pathogen that is widespread all over the world, infecting more than 50% of the world’s population. It is etiologically associated with non-atrophic and atrophic gastritis, peptic ulcer and shows a deep association with primary gastric B-cell lymphoma and gastric adenocarcinoma. Recently, the medical research focused on the modification of the gastric environment induced by H. pylori infection, possibly affecting the absorption of nutrients and drugs as well as the production of hormones strongly implicated in the regulation of appetite and growth. Interestingly, the absorption of iron and vitamin B12 is impaired by H. pylori infection, while infected subjects have lower basal and fasting serum levels of ghrelin and higher concentration of leptin compared to controls. Since leptin is an anorexigenic hormone, and ghrelin stimulates powerfully the release of growth hormone in humans, H. pylori infection may finally induce growth retardation if acquired very early in the childhood and in malnourished children. This review is focused on the nutritional effects of H. pylori infection, such as the reduced bioavailability or the malabsorbption of essential nutrients, and of gastrointestinal hormones, as well as on the relationship between H. pylori and the metabolic syndrome. PMID:25278679
Ohno, Tomoyuki; Kita, Masakazu; Yamaoka, Yoshio; Imamura, Shigeyoshi; Yamamoto, Toshiro; Mitsufuji, Shoji; Kodama, Tadashi; Kashima, Kei; Imanishi, JirO
Helicobacter pylori is an important pathogen responsible for gastroduodenal diseases in humans. Although the eradication of H. pylori using antibiotics often improves gastroduodenal diseases, resistance to the antibiotics is emerging. The antimicrobial effect of essential oils and the development of resistance to the essential oils were evaluated in vitro and in vivo. Thirteen essential oils used in this study completely inhibited the growth of H. pylori in vitro at a concentration of 0.1% (v/v). Cymbopogon citratus (lemongrass) and Lippia citriodora (lemon verbena) were bactericidal against H. pylori at 0.01% at pH 4.0 and 5.0. Resistance to lemongrass did not develop even after 10 sequential passages, whereas resistance to clarithromycin developed under the same conditions. In in vivo studies, the density of H. pylori in the stomach of mice treated with lemongrass was significantly reduced compared with untreated mice. These results demonstrate that the essential oils are bactericidal against H. pylori without the development of acquired resistance, suggesting that essential oils may have potential as new and safe agents for inclusion in anti-H. pylori regimens.
Hu, Yue; Zhang, Meng; Lu, Bin; Dai, Jinfeng
Helicobacter pylori, a human pathogen with a high global prevalence, is the causative pathogen for multiple gastrointestinal diseases, especially chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric malignancies. Antibiotic therapies remain the mainstay for H. pylori eradication; however, this strategy is hampered by the emergence and spread of H. pylori antibiotic resistance. Exploring the mechanistic basis of this resistance is becoming one of the major research questions in contemporary biomedical research, as such knowledge could be exploited to devise novel rational avenues for counteracting the existing resistance and devising strategies to avoid the development of a novel anti-H. pylori medication. Encouragingly, important progress in this field has been made recently. Here, we attempt to review the current state and progress with respect to the molecular mechanism of antibiotic resistance for H. pylori. A picture is emerging in which mutations of various genes in H. pylori, resulting in decreased membrane permeability, altered oxidation-reduction potential, and a more efficient efflux pump system. The increased knowledge on these mechanisms produces hope that antibiotic resistance in H. pylori can ultimately be countered. © 2016 John Wiley & Sons Ltd.
Delitala, Alessandro P.; Pes, Giovanni M.; Malaty, Hoda M.; Pisanu, Gavino; Delitala, Giuseppe; Dore, Maria P.
Background. Type 1 diabetes (T1D) and type 2 diabetes (T2D) have been linked to Helicobacter pylori infection, although results are conflicting. No previous study addressed a possible link between H. pylori infection and latent autoimmune diabetes in adults (LADA). In this study, a correlation among H. pylori infection and the risk of autoimmune diabetes in comparison with T2D was investigated. Methods. Sera from 234 LADA patients, 105 patients with late-onset T1D, and 156 patients with T2D were analyzed for anti-H. pylori and the cytotoxin-associated antigen (CagA) IgG antibodies. Results. H. pylori seroprevalence was comparable in LADA (52%), late-onset T1D (45%), and T2D (49%) with no gender differences. The seroprevalence of CagA IgG was significantly higher in autoimmune diabetes (late-onset T1D: 45%, LADA: 40%) compared to T2D (25%; p < 0.028). Conclusions. Although H. pylori seroprevalence was similar in LADA, T1D, and T2D, anti-CagA positivity was significantly increased among patients with autoimmune diabetes, suggesting that more virulent H. pylori strains might be a trigger for immune mechanisms involved in their pathogenesis. PMID:26824048
Rathbone, B.; Martin, D.; Stephens, J.; Thompson, J. R.; Samani, N. J.
OBJECTIVE: To determine whether Helicobacter pylori infection increases the risk of myocardial infarction. DESIGN: Case-control study. SETTING: University teaching hospital. METHODS: Serological evidence of H pylori infection was determined in 342 consecutive patients with acute myocardial infarction admitted into the coronary care unit and in 236 population-based controls recruited from visitors to patients on medical and surgical wards. RESULTS: 206/342 (60.2%) of cases were H pylori positive compared with 132/236 (55.9%) of controls (P = 0.30). Age and sex stratified odds ratio for myocardial infarction associated with H pylori seropositivity was 1.05 (95% CI 0.7 to 1.53, P = 0.87) and this remained non-significant (P = 0.46) when other risk factors for ischaemic heart disease were taken into account using logistic regression analysis. H pylori seropositivity was not associated with several coronary risk factors in either cases or controls. CONCLUSION: No increase was found in H pylori seropositivity in subjects with acute myocardial infarction. This suggests that previous H pylori infection is not a major risk factor for acute myocardial infarction. Images PMID:8983674
Camargo, M Constanza; Constanza, Camargo M; Lazcano-Ponce, Eduardo; Eduardo, Lazcano-Ponce; Torres, Javier; Javier, Torres; Velasco-Mondragon, Eduardo; Eduardo, Velasco-Mondragón; Quiterio, Manuel; Manuel, Quiterio; Correa, Pelayo; Pelayo, Correa
Helicobacter pylori infection is one of the most common human infections and is considered to play an etiologic role in several gastroduodenal diseases. In this study we determined the H. pylori seroprevalence among adolescents in Morelos, Mexico, and explored the association between seroprevalence and socioeconomic, dietary and lifestyle variables. A cross-sectional study was conducted in 5861 Mexican subjects aged 11-21 years. H. pylori infection was determined by an enzyme-linked immunosorbent assay previously validated in Mexico. A self-administered questionnaire was used to collect information on sociodemographic factors, housing, living conditions and food consumption. Multivariate logistic regression methods were used to obtain odds ratios and 95% confidence intervals. The overall H. pylori seroprevalence was 47.6%; 40.6% in preadolescents (11-14 years), 48.6% in adolescents (15-17 years), and 59.8% in young adults (18-24 years). A positive association was found between age and H. pylori seroprevalence. Inverse associations were found for availability of drinking water, sewerage, and home appliances at the time of the subject's birth, a proxy variable of socioeconomic status. Intake of milk products and total fats was positively associated with infection. This large seroprevalence study showed that H. pylori infection is frequent among adolescents in Mexico. An early acquisition of infection is indirectly suggested. Some variables denoting low socioeconomic status were inversely associated with H. pylori seroprevalence. Associations with intake of milk products and total fats suggest new hypotheses in this field of research.
Rispo, Antonio; Capone, Pietro; Castiglione, Fabiana; Pasquale, Luigi; Rea, Matilde; Caporaso, Nicola
Helicobacter pylori (H. pylori) is a widespread pathogen infecting about 40% of people living in urban areas and over 90% of people living in the developing regions of the world. H. pylori is well-documented as the main factor in the pathogenesis of peptic ulcer disease, chronic gastritis, and gastric malignancies such as cancer and mucosa-associated lymphoid tissue-lymphoma; hence, its eradication is strongly recommended. The Maastricht IV consensus, which focused on the management of H. pylori infection, set important new strategies in terms of treatment approaches, particularly with regards to first- and second-line treatment protocols and led to improved knowledge and understanding of H. pylori resistance to antibiotics. In recent years, various fluoroquinolone-based protocols, mainly including levofloxacin, have been proposed and effectively tested at all therapeutic lines for H. pylori eradication. The aim of the present paper is to review the scientific literature focused on the use of fluoroquinolones in eradicating H. pylori. PMID:25083067
Goswami, Suchandra; Chinniah, Annalakshmi; Pal, Anirban; Kar, Sudip K.
The antimalarial drug artemisinin from Artemisia annua demonstrated remarkably strong activity against Helicobacter pylori, the pathogen responsible for peptic ulcer diseases. In an effort to develop a novel antimicrobial chemotherapeutic agent containing such a sesquiterpene lactone endoperoxide, a series of analogues (2 natural and 15 semisynthetic molecules), including eight newly synthesized compounds, were investigated against clinical and standard strains of H. pylori. The antimicrobial spectrum against 10 H. pylori strains and a few other bacterial and fungal strains indicated specificity against the ulcer causing organism. Of five promising molecules, a newly synthesized ether derivative β-artecyclopropylmether was found to be the most potent compound, which exhibited MIC range, MIC90, and minimum bactericidal concentration range values of 0.25 to 1.0 μg/ml, 1.0 μg/ml, and 1 to 16 μg/ml, respectively, against both resistant and sensitive strains of H. pylori. The molecule demonstrated strong bactericidal kinetics with extensive morphological degeneration, retained functional efficacy at stomach acidic pH unlike clarithromycin, did not elicit drug resistance unlike metronidazole, and imparted sensitivity to resistant strains. It is not cytotoxic and exhibits in vivo potentiality to reduce the H. pylori burden in a chronic infection model. Thus, β-artecyclopropylmether could be a lead candidate for anti-H. pylori therapeutics. Since the recurrence of gastroduodenal ulcers is believed to be mainly due to antibiotic resistance of the commensal organism H. pylori, development of a candidate drug from this finding is warranted. PMID:22687518
Poutahidis, T; Tsangaris, T; Kanakoudis, G; Vlemmas, I; Iliadis, N; Sofianou, D
A conventional nonmutant animal that could be experimentally infected with Helicobacter pylori isolates would be a useful animal model for human H. pylori-associated gastritis. Gnotobiotic and barrier-born pigs are susceptible to H. pylori infection, but attempts to infect conventional pigs with this bacterium have been unsuccessful. In the present study, a litter of eight 20-day-old crossbreed piglets were purchased from a commercial farm. Six of them were orally challenged two to five times at different ages, between 29 and 49 days, with doses of H. pylori inoculum containing approximately 10(9) bacterial cells. Two animals served as controls. The inoculation program began 2 days postweaning when the piglets were 29 days of age. Prior to every inoculation, the piglets were fasted and pretreated with cimetidine, and prior to the first and second inoculation each piglet also was pretreated with dexamethasone. The challenged piglets were euthanasized between 36 and 76 days of age. H. pylori colonized all six inoculated piglets. The pathology of the experimentally induced gastritis was examined macroscopically and by light and electron microscopy. H. pylori induced a severe lymphocytic gastritis in the conventional piglets and reproduced the large majority of the pathologic features of the human disease. Therefore, the conventional piglet represents a promising new model for study of the various pathogenic mechanisms involved in the development of lesions of the human H. pylori-associated gastritis.
Elseweidy, Mohamed M; Taha, Mona M; Younis, Nahla N; Ibrahim, Khadiga S; Hamouda, Hamdi A; Eldosouky, Mohamed A; Soliman, Hala
Gastritis, an inflammation of gastric mucosa, may be due to many pathological factors and infection, such as with Helicobacter pylori. The use of experimental models of gastritis is important to evaluate the biochemical changes and study chemotherapeutic intervention. In a previous study we demonstrated an acute gastritis model induced by iodoacetamide. Our objective in this study was to evaluate a new gastritis model induced by H. pylori infection in experimental rats in terms of certain biomarkers in serum and mucosal tissues in addition to histopathological examination. Gastritis was induced in 20 albino Wistar rats by H. pylori isolated from antral biopsy taken from a 49-year-old male patient endoscopically diagnosed as having H. pylori infection. Another ten rats were used as controls. Serum gastrin, pepsinogen I activity, interleukin-6 (IL-6) and gastric mucosal myeloperoxidase (MPO) activity and prostaglandin E(2) (PGE(2)) were measured. Immunostaining for inducible nitric oxide synthase (iNOS), nitrotyrosine and DNA fragmentation were used to further evaluate H. pylori-induced gastritis. Serum gastrin, IL-6, mucosal MPO activity, and PGE(2) demonstrated significant increases joined with a decreased serum pepsinogen I activity (P < 0.001). Immunohistochemistry demonstrated positive reaction for iNOS, nitrotyrosine and DNA fragmentation. Helicobacter pylori-induced gastritis models demonstrated massive oxidative stress and pronounced injury in mucosal tissue. Since our model in rats reflected the clinical picture of H. pylori infection, it can be considered as a consistent model to study chemotherapeutic intervention for this type of gastritis.
Bui, David; Brown, Heidi E.; Harris, Robin B.; Oren, Eyal
Helicobacter pylori infection is among the most prevalent infections in the world and a key cause of gastric diseases; however, its route of transmission remains unclear. This study aimed to assess the potential for fecal–oral transmission of H. pylori by leveraging its association with a disease with known etiology. Utilizing serology data from the National Health and Nutrition Examination Survey (NHANES 1999; N = 6,347), the association between H. pylori and hepatitis A virus (HAV), a sensitive indicator for fecal–oral exposure, was assessed. Survey-weighted kappa and multiple logistic regression were used to quantify the association between H. pylori and HAV after controlling for age, sex, race, poverty, birthplace, crowding, smoking, and alcohol use. Concordant serological results were found among 69.8% of participants (survey-weighted κ = 0.30, 95% confidence interval [CI] = 0.26, 0.35). The adjusted odds of H. pylori seropositivity were over two times higher after adjusting for confounders (odds ratio = 2.27, 95% CI = 1.79, 2.87). Results from this study suggest H. pylori and HAV infections are strongly associated. Since HAV is primarily transmitted through the fecal–oral route, fecal–oral transmission may be an important pathway for H. pylori spread. PMID:26598563
Wang, Jing; Wang, Wei-Hong; Li, Jiang; Liu, Fang-Xun
AIM: To investigate the effect of celecoxib, a selective COX-2 inhibitor, on Helicobacter pylori (H. pylori) colonization-related factors and its mechanism. METHODS: After co-incubation with celecoxib, morphology of H. pylori strain 26695 was observed under a transmission electron microscope. Flagella motility was assessed by stab agar motility test. Adherence of H. pylori to AGS cells was determined by enzyme linked immunosorbent assay. Levels of mRNA expression in flagellar genes (flaA, flaB), urease genes (ureA, ureB) and adhesin genes (babA, sabA, alpA, alpB, hpaA, hopZ) were measured by real-time polymerase chain reaction. RESULTS: Separation and non-integrity of bacterial cell wall, rarefaction and asymmetry of cytoplasm, and even lysis of H. pylori were observed in the presence of celecoxib. When H. pylori strains were incubated in the presence of celecoxib, their flagellar motility and adherence to AGS cells were inhibited. The expression of ureA, ureB, babA, sabA, alpA, alpB, hpaA, hopZ was up-regulated while the expression of flaA, flaB was down-regulated in the presence of celecoxib. CONCLUSION: Celecoxib inhibits flagellar motility and adherence of H. pylori to AGS cells, and destructs their normal structure in vitro. PMID:20143463
Dunn, B. E.; Phadnis, S. H.
Helicobacter pylori is the causative agent of most cases of gastritis. Once acquired, H. pylori establishes chronic persistent infection; it is this long-term infection that, is a subset of patients, leads to gastric or duodenal ulcer, gastric cancer or gastric MALT lymphoma. All fresh isolates of H. pylori express significant urease activity, which is essential to survival and pathogenesis of the bacterium. A significant fraction of urease is associated with the surface of H. pylori both in vivo and in vitro. Surface-associated urease is essential for H. pylori to resist exposure to acid in the presence of urea. The mechanism whereby urease becomes associated with the surface of H. pylori is unique. This process, which we term "altruistic autolysis," involves release of urease (and other cytoplasmic proteins) by genetically programmed autolysis with subsequent adsorption of the released urease onto the surface of neighboring intact bacteria. To our knowledge, this is the first evidence of essential communal behavior in pathogenic bacteria; such behavior is crucial to understanding the pathogenesis of H. pylori. PMID:10378351
Ranjbar, Reza; Behzadi, Payam; Farshad, Shohreh
Helicobacter pylori is a Gram-negative motile bacterium causative agent of acute and chronic digestive and extra-digestive human infections. According to different reports worldwide, H. pylori symptomatic and asymptomatic infections are a global problem. The statistical investigations show a percentage of 50 for people who are involved in H. pylori acute/chronic digestive and/or extra-digestive infections around the world. This review focuses on digestive and extra-digestive diseases caused by H. pylori, the related virulence factors, diagnostic techniques including non-invasive and invasive diagnostics and treatment. There is an abundance of diagnostics for detection and identification of H. pylori. The availability, cost, and the condition of test performance may differ from place to place. To increase the level of reliability in association with diagnostic tools for detecting H. pylori, several techniques must be applied at once as multi-diagnostic technique. Furthermore, there are several pharmacotherapies which can be used for complete eradication of H. pylori infection.
Enany, Shymaa; Abdalla, Salah
Helicobacter pylori is one of the most common causes of chronic infections in humans. Curing H. pylori infection is difficult because of the habitat of the organism below the mucus adherent layer of gastric mucosa. Lactobacilli are known as acid-resistant bacteria and can remain in stomach for a long time than any other organism, we aimed in this study to examine the efficacy of Lactobacillus casei as a probiotic against H. pylori in humans. Particularly, L. casei was opted as it is considered to be one of the widely used probiotics in dairy products. One hundred and seven strains of H. pylori were isolated from dyspeptic patients and were tested for their antibiotic susceptibility to metronidazole (MTZ), clarithromycin (CLR), tetracycline (TET), and amoxicillin (AMX) by the disc diffusion method. The strains were examined for their susceptibility toward L. casei - present in fermented milk products - by well diffusion method. It was found that 74.7% strains were resistant to MTZ; 1.8% to MTZ, TET, and CLR; 3.7% to MTZ and CLR; 4.6% to MTZ and TET; and 0.9% were resistant to MTZ, TET, and AMX. The antibacterial activity of L. casei against H. pylori was determined on all the tested H. pylori isolates including antibiotic resistant strains with different patterns. Our study proposed the use of probiotics for the treatment of H. pylori infection as an effective approach. PMID:26691482
Kuipers, E J; Uyterlinde, A M; Peña, A S; Roosendaal, R; Pals, G; Nelis, G F; Festen, H P; Meuwissen, S G
Chronic Helicobacter pylori gastritis has been put forward as a risk factor for development of gastric mucosal atrophy and gastric cancer. The purpose of our study was to investigate the long-term effects of H pylori gastritis on the gastric mucosa. We prospectively studied 49 subjects negative for H pylori and 58 positive subjects for a mean follow-up of 11.5 years (range 10-13 years). Serum samples were obtained at the initial and follow-up visits for determination of H pylori IgG antibodies. Gastroscopies with biopsy sampling were done in all patients at both visits. Biopsy specimens were used for assessment of H pylori infection and histology. Development of atrophic gastritis and intestinal metaplasia occurred in 2 (4%) uninfected and 16 (28%) infected subjects. Regression of atrophy was noted in 4 (7%) infected subjects. Development of atrophic gastritis and intestinal metaplasia was significantly associated with H pylori infection (p = 0.0014; odds ratio 9.0, 95% CI 1.9-41.3). The proportion of atrophic gastritis in the study population showed an annual increase of 1.15% (0.5-1.8%). We conclude that H pylori infection is a significant risk factor for development of atrophic gastritis and intestinal metaplasia. Our findings support strongly the causative role of this infection in gastric carcinogenesis.
Boehnke, Kevin F; Eaton, Kathryn A; Valdivieso, Manuel; Baker, Laurence H; Xi, Chuanwu
Helicobacter pylori infection has been consistently associated with lack of access to clean water and proper sanitation, but no studies have demonstrated that the transmission of H. pylori can occur from drinking contaminated water. In this study, we used a laboratory mouse model to test whether waterborne H. pylori could cause gastric infection. Groups of immunocompetent C57/BL6 Helicobacter-free mice were exposed to static concentrations (1.29 × 10(5), 10(6), 10(7), 10(8), and 10(9) CFU/L) of H. pylori in their drinking water for 4 weeks. One group of Helicobacter-free mice was exposed to uncontaminated water as a negative control. H. pylori morphology changes in water were examined using microscopy Live/Dead staining. Following exposure, H. pylori infection and inflammation status in the stomach were evaluated using quantitative culture, PCR, the rapid urease test, and histology. None of the mice in the negative control or 10(5) groups were infected. One of 20 cages (one of 40 mice) of the 10(6) group, three of 19 cages (four of 38 mice) of the 10(7) CFU/L group, 19 of 20 cages (33 of 40 mice) of the 10(8) group, and 20 of 20 cages (39 of 40 mice) of the 10(9) CFU/L group were infected. Infected mice had significantly higher gastric inflammation than uninfected mice (27.86% higher inflammation, p < .0001). We offer proof that H. pylori in water is infectious in mice, suggesting that humans drinking contaminated water may be at risk of contracting H. pylori infection. Much work needs to be performed to better understand the risk of infection from drinking H. pylori-contaminated water. © 2015 John Wiley & Sons Ltd.
Suzuki, Rumiko; Shiota, Seiji; Yamaoka, Yoshio
Helicobacter pylori infection is linked to various gastroduodenal diseases; however, only approximately 20% of infected individuals develop severe diseases. Despite the high prevalence of H. pylori infection in Africa and South Asia, the incidence of gastric cancer in these areas is much lower than in other countries. Furthermore, the incidence of gastric cancer tends to decrease from north to south in East Asia. Such geographic differences in the pathology can be explained, at least in part, by the presence of different types of H. pylori virulence factors, especially cagA, vacA, and the right end of the cag pathogenicity island. The genotype of the virulence genes is also useful as a tool to track human migration utilizing the high genetic diversity and frequent recombination between different H. pylori strains. Multilocus sequence typing (MLST) analysis using 7 housekeeping genes can also help predict the history of human migrations. Population structure analysis based on MLST has revealed 7 modern population types of H. pylori, which derived from 6 ancestral populations. Interestingly, the incidence of gastric cancer is closely related to the distribution of H. pylori populations. The different incidence of gastric cancer can be partly attributed to the different genotypes of H. pylori circulating in different geographic areas. Although approaches by MLST and virulence factors are effective, these methods focus on a small number of genes and may miss information conveyed by the rest of the genome. Genome-wide analyses using DNA microarray or whole-genome sequencing technology give a broad view on the genome of H. pylori. In particular, next-generation sequencers, which can read DNA sequences in less time and at lower costs than Sanger sequencing, enabled us to efficiently investigate not only the evolution of H. pylori, but also novel virulence factors and genomic changes related to drug resistance. PMID:22197766
Helicobacter pylori is one of the most common human infections worldwide. It has been established as etiology of chronic gastritis and peptic ulcer disease, gastric adenocarcinoma and mucosal associated lymphoid tissue lymphoma (MALT). During this decade, there have been some reports showing a decline in global prevalence of H. pylori infection and peptic diseases including in many Asian countries. To study the H. pylori infection in patients with peptic diseases, association with other factors and comparison to previous data. Retrospective observational study of endoscopic reports for upper gastrointestinal tract diseases in patients with peptic diseases from October 2009 to September 2010 at the Endoscopic Unit, Department of Medicine, Rajavithi Hospital. Patients were examined for the presence of H. pylori infection by rapid urease test (RUT) or histology staining. Five hundred and seventy patients with a mean age of 55.0 +/- 16.02 years with peptic diseases were studies. Endoscopic findings showed 106 GU patients (18.6%), 29 DU patients (5.1%), 3 combined GU and DU patients (0.5%) and 432 NUD patients (75.8%). The prevalence of H. pylori infection were 64% (365 of 570 patients). Prevalence of H. pylori infection were 61.3% of NUD cases, 68.9% of GU cases, 82.8% in DU cases and 100% in combined GU and DU cases. Comparison with previous data (Anantapunpong S. Rajavithi Med J 1999; 10: 17-26), the prevalence of H. pylori infection overall and in DU are not changed but in NUD and GU are increased. The prevalence of H. pylori infection is still high in peptic diseases. The patients with age more than 50 years have more GU, less NUD than the younger groups. In comparison with a previous study, the prevalence of H. pylori infection in overall and in DU are not changed but in NUD and GU are increased.
Slomiany, B L; Murty, V L; Piotrowski, J; Slomiany, A
1. Convincing evidence now exists that infection with H. pylori plays a major role in the pathogenesis of gastric disease. Having a niche bordering two major perimeters of mucosal defenses, the bacterium apparently exerts its detrimental effect on the mucus layer as well as the gastric epithelium. Therefore, gastroprotective agents capable of counteracting these detrimental effects of H. pylori are gaining importance in the treatment of gastric disease. 2. The colonization of gastric mucosa by H. pylori involves specific glycolipid receptors bearing acidic substituents, a process inhibited by gastric sulfomucins. Two antiulcer agents bearing sulfated sugar groups have been demonstrated to possess the ability to interfere with H. pylori colonization process. These are sucralfate and sulglycotide. The two agents are also potent inhibitors of H. pylori glycosulfatase activity directed against indigenous mucosal defenses. 3. A variety of extracellular enzymes such as proteases, lipases and phospholipases, elaborated by H. pylori cause the weakening of the integrity of gastric mucus coat and render the underlying epithelium vulnerable to noxious luminal contents. Among the most potent agents capable of countering the proteolytic activity of H. pylori are nitecapone, ebrotidine and sulglycotide, while ebrotidine and sulglycotide were found to be most effective inhibitors of H. pylori lipolytic activities. 4. The gastric epithelial integrity is compromized by the H. pylori cell-wall lipopolysaccharide untoward effect on the epithelial surface receptors. The interference of the lipopolysaccharide with the laminin receptor was found to be most efficiently countered by ebrotidine, sulglycotide and sucralfate, whereas sulglycotide is the most potent in the reversal of the inhibitory effect of the lipopolysaccharide on mucin receptor binding.
Mangia, Anita; Chiriatti, Annalisa; Ranieri, Girolamo; Abbate, Ines; Coviello, Maria; Simone, Giovanni; Zito, Francesco Alfredo; Montemurro, Severino; Rucci, Antonello; Leo, Alfredo Di; Tommasi, Stefania; Berloco, Pasquale; Xu, Jian Ming; Paradiso, Angelo
AIM: To investigate H pylori expression in gastric cancer patients in relation to primary tumor angiogenic markers, such as microvessel density (MVD), thymidine phosphorylase (TP), vascular endothelial growth factor receptor-1 (VEGF-R1), p53 and circulating VEGF levels. METHODS: Angiogenic markers were analyzed immunohistochemically in 56 primary gastric cancers. H pylori cytotoxin (vacA) and the cytotoxin-associated gene (cagA) amplification were evaluated using PCR assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels were detected in 39 and 38 patients by ELISA, respectively. RESULTS: A total of 69% of patients were positive for circulating IgG antibodies against H pylori. cagA-positive H pylori strains were found in 41% of gastric patients. vacA was found in 50% of patients; s1 strains were more highly expressed among vacA-positive patients. The presence of the s1 strain was significantly associated with cagA (P = 0.0001). MVD was significantly correlated with both tumor VEGF expression (r = 0.361, P = 0.009) and serum VEGF levels (r = -0.347, P = 0.041). Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression. However, H pylori was not related to any angiogenic markers except for the plasma VEGF level (P = 0.026). CONCLUSION: H pylori antigen is related to higher plasma VEGF levels, but not to angiogenic characteristics. It can be hypothesized that the toxic effects of H pylori on angiogenesis occurs in early preclinical disease phase or in long-lasting aggressive infections, but only when high H pylori IgG levels are persistent. PMID:17006982
Lupu, V V; Ignat, A; Ciubotariu, G; Ciubară, A; Moscalu, M; Burlea, M
Some studies suggest that Helicobacter pylori (H. pylori) infection would be a protective factor for the gastroesophageal reflux. The aim of this study was to explore this fact. A group of 72 children, admitted in a pediatric gastroenterology regional center in Northeast Romania, diagnosed with gastroesophageal reflux by 24-hour continuous esophageal pH monitoring (results were interpreted using the Boix-Ochoa score), underwent upper endoscopy with gastric biopsy to detect the presence of H. pylori by the rapid urease testing and for bacteriological and histologic examination. 19 children (26.39%) had H. pylori infection, while 53 (73.61%) did not. The grade of esophagitis was classified according to the Los Angeles classification system. Out of 47 children with esophagitis A, 16 (34.04%) had H. pylori infection, while out of the 25 children with esophagitis B, only 3 (12%) had H. pylori infection, with statistic significance (χ(2) = 54.69, P < 0.05, 95% confidence interval [CI]). Regarding the value of the Boix-Ochoa score, it appears that the presence of the H. pylori determines lower pH-metry scores (F = 8.13, P = 0.0015, 95% CI). The presence of the H. pylori was not an important factor in the gastroesophageal reflux. On the other hand its relationship with esophagitis appears to be inverse ratio. The fact that the H. pylori presence is statistically greater in the grade A esophagitis could confirm the hypothesis that the bacteria would slow down the development of the esophagitis. © 2015 International Society for Diseases of the Esophagus.
Kalkan, Ismail Hakki; Sapmaz, Ferdane; Güliter, Sefa; Atasoy, Pınar
In several studies, different risk factors other than antibiotic resistance have been documented with Helicobacter pylori eradication failure. We aimed in this study to investigate the relationship of gastric density of H. pylori, the occurrence/degree of gastric atrophy, and intestinal metaplasia (IM) with success rate of H. pylori eradication. Two hundred consecutive treatment naive patients who received bismuth containing standart quadruple treatment due to H. pylori infection documented by histopathological examination of two antral or two corpal biopsies entered this retrospective study. The updated Sydney system was used to grade the activity of gastritis, density of H. pylori colonization, atrophy, and IM. Stages III and IV of operative link for gastritis assessment (OLGA) or the operative link on gastric intestinal metaplasia assessment (OLGIM) stages was considered as severe gastritis. H. pylori eradication was determined via stool H. pylori antigen test performed 4 weeks after the end of therapy. The presence of gastric atrophy and IM was significantly higher in patients with eradication failure (p = 0.001 and 0.01, respectively). Severe gastritis (OLGA III-IV and OLGIM III-IV) rates were higher in eradication failure group. A multiple linear regression analysis showed that OLGA and OLGIM stages were to be independent risk factors for eradication failure (p = 0.03 and 0.01, respectively). Our results suggested that histopathologically severe gastritis may cause H. pylori eradication failure. In addition, we found that H. pylori density was not a risk factor for treatment failure in patients who receive quadruple treatment.
Jiang, Zheng; Tao, Xiao-Hong; Huang, Ai-Long; Wang, Pi-Long
AIM: To construct a recombinant vector which can express Mr26000 outer membrane protein (OMP) from Helicobacter pylori (H. pylori), and to obtain the vaccine protecting against H. pylori infection and a diagnostic reagent kit quickly detecting H. pylori infection. METHODS: The gene encoding the structural Mr26000 outer membrane protein of H. pylori was amplified from H. pylori chromosomal DNA by PCR, and inserted in the prokaryotic expression vector pET32a(+), which was transformed into the Top10 E. coli strain. Recombinant vector was selected, identified and transformed into BL-21(DE3) E. coli strain. The recombinant fusion proteins were expressed. The antigenicity of recombinant protein was studied by ELISA or immunoblotting and immunized Balb/c mice. RESULTS: The gene of Mr26000 OMP was amplified to be 594 base pairs, 1.1% of the cloned genes was mutated and 1.51% of amino acid residues was changed, but there was homogeneity between them. The recombinant fusion protein encoded objective polypeptides of 198 amino acid residues, corresponding to calculated molecular masses of Mr26000. The level of soluble expression products was about 38.96% of the total cell protein. After purification by Ni-NTA agarose resin columniation, the purity of objective protein became about 90%. The ELISA results showed that recombinant fusion protein could be recognized by patient serum infected with H. pylori and rabbit serum immunized with the recombinant protein. Furthermore, Balb/c mice immunized with the recombinant protein were protected against H. pylori infection. CONCLUSION: Mr26000 OMP may be a candidate vaccine preventing H. pylori infection. PMID:11925614
Mearin, F; de Ribot, X; Balboa, A; Salas, A; Varas, M J; Cucala, M; Bartolomé, R; Armengol, J R; Malagelada, J R
The role of Helicobacter pylori infection in the pathogenesis of functional dyspepsia is debated. It is known that a substantial fraction of dyspeptic patients manifest a low discomfort threshold to gastric distension. This study investigated the symptomatic pattern in 27 H pylori positive and 23 H pylori negative patients with chronic functional dyspepsia, and potential relations between infection and gastric hyperalgesia. Specific symptoms (pain, nausea, vomiting, bloating/fullness, early satiety) were scored from 0 to 3 for severity and frequency (global symptom scores: 0-15). The mechanical and perceptive responses to gastric accommodation were evaluated with an electronic barostat that produced graded isobaric distensions from 0 to 20 mm Hg in 2 mm Hg steps up to 600 ml. Gastric compliance (volume/pressure relation) and perception (rating scale: 0-10) were quantified. Standard gastrointestinal manometry and recorded phasic pressure activity at eight separate sites during fasting and postprandially were also assessed. H pylori positive and H pylori negative patients manifested similar severity and frequency of specific symptoms and global symptom scores (mean (SEM)) (severity: 9.5 (2.0) v 9.0 (2.1); frequency: 10.8 (2.0) v 9.7 (2.2)). No differences were seen either in gastric compliance (53 (4) ml/mm Hg v 43 (3) ml/mm Hg) or in gastric perception of distension (slope: 0.50 (0.05) v 0.53 (0.06)). Postprandial antral motility was significantly decreased in H pylori positive patients (two hours motility index: 10.4 (0.6) v 12.6 (0.5); p < 0.05). It is concluded that H pylori infected patients with functional dyspepsia present no distinctive symptoms by comparison with H pylori negative counterparts and H pylori infection is associated with diminished postprandial antral motility but it does not increase perception of gastric distension. PMID:7672680
Jiang, Xiuping; Doyle, Michael P
The survival and growth of Helicobacter pylori under enrichment conditions in fresh, autoclaved and irradiated ground beef were determined. H. pylori grew in autoclaved ground beef at 37 degrees C under microaerobic conditions in brain heart infusion broth with 7% horse serum at pH 7.3 after 3 to 7 days of lag time but did not grow within 7 days in irradiated (10 kGy) ground beef under the same enrichment conditions. Adjustment of the enrichment broth to pH 5.5 enabled the growth (ca. 2 log10 CFU/ml) of H. pylori within 7 days in the presence of irradiated ground beef and the prolific growth (ca. 3 to 4 log10 CFU/ml) of H. pylori within 3 days in the presence of autoclaved beef. H. pylori in fresh ground beef could not be isolated from enrichment media with antibiotics; however. H. pylori ureA could be detected by polymerase chain reaction (PCR) in such enrichment media after 1 to 3 days of incubation at 37 degrees C. The addition of supplements, i.e., 0.3% mucin, 0.05% ferrous sulfate, and 0.05% sodium pyruvate or 0.008 M urea, or the adjustment of the enrichment broth pH to 5.5 or 4.5 enabled the detection of H. pylori ureA in enrichment media incubated for 1, 2, 3, and/or 7 days at 37 degrees C. H. pylori in sterile milk refrigerated at 4 degrees C at an initial level of 10(6) CFU/ml was inactivated to an undetectable level within 6 days; however, H. pylori was not detected either by a PCR assay or by the plating of enrichment cultures of 120 raw bovine milk samples.
Reva, I V; Yamamoto, T; Vershinina, S S; Reva, G V
We present the results of electron microscopic, microbiological, immunohistochemical, and molecular genetic studies of gastric biopsy specimens taken for diagnostic purposes according by clinical indications during examination of patients with gastrointestinal pathology. Immune homeostasis of the gastric mucosa against the background of infection with various pathogen strains of Helicobacter pylori was studied in patients of different age groups with peptic ulcer, gastritis, metaplasia, and cancer. Some peculiarities of Helicobacter pylori contamination in the gastric mucosa were demonstrated. Immune homeostasis of the gastric mucosa in different pathologies was analyzed depending on the Helicobacter pylori genotype.
Franchini, Massimo; Vescovi, Pier Paolo; Garofano, Massimo; Veneri, Dino
The Gram-negative bacterium Helicobacter pylori has a well-demonstrated role in several gastroduodenal diseases, including peptic ulcer disease, chronic active gastritis, mucosa-associated lymphoid tissue lymphoma, and gastric adenocarcinoma. In addition, more recently, several studies have focused on the possible causal role of H. pylori in various extragastric disorders, such as cardiovascular, respiratory, neurological, skin, and autoimmune conditions. The current status of the research on the pathogenesis, clinical and therapeutic aspects of H. pylori-associated idiopathic thrombocytopenic purpura in adults and children will be addressed in this narrative review.
Fock, Kwong Ming; Graham, David Y; Malfertheiner, Peter
Helicobacter pylori leads to chronic gastritis, peptic ulcer disease and gastric cancer. With increasing issues of antibiotic resistance and changing epidemiology of this pathogen, new approaches are needed for effective management. In 1984, Dr Barry Marshall and Dr Robin Warren reported the association of Helicobacter pylori with peptic ulcers in The Lancet--a discovery that earned them the Nobel prize in Physiology or Medicine in 2005--but what progress have we made since then? Here, we have invited three international experts to give their insights into the advances in H. pylori research over the past 30 years and where research should be focused in the future.
Marone, P; Bono, L; Leone, E; Bona, S; Carretto, E; Perversi, L
In this study we evaluated the antibacterial activity of mastic gum, a resin obtained from the Pistacia lentiscus tree, against clinical isolates of Helicobacter pylori. The minimal bactericidal concentrations (MBCs) were obtained by a microdilution assay. Mastic gum killed 50% of the strains tested at a concentration of 125 microg/ml and 90% at a concentration of 500 microg/ml. The influence of sub-MBCs of mastic gum on the morphologies of H. pylori was evaluated by transmission electron microscopy. The lentiscus resin induced blebbing, morphological abnormalities and cellular fragmentation in H. pylori cells.
Ramírez Ramos, Alberto; Sánchez Sánchez, Rolando
We have reviewed Lilacs, PubMed and Google searching for original articles related to Helicobacter pylori published by Latin American investigators from 2003 to 2008. Contributions in the following fields by countries are: Molecular biology: Brasil, Chile, Colombia, Peru y Venezuela. Argentina, Brasil, Colombia, Cuba, Peru y Venezuela. Argentina, Bolivia, Brasil, Chile, Costa Rica, Colombia, Mexico, Peru y Venezuela. Helicobacter pylori and gastroduodenal diseases: Brasil, Cuba, Peru y Venezuela. Helicobacter pylori and extra digestive diseases: Brasil, Colombia and Venezuela. Pediatrics: Brasil, Cuba y Venezuela. Argentina, Brasil, Chile, Colombia, Costa Rica, Mexico, Peru y Venezuela.
Fock, Kwong Ming; Graham, David Y.; Malfertheiner, Peter
Helicobacter pylori leads to chronic gastritis, peptic ulcer disease and gastric cancer. With increasing issues of antibiotic resistance and changing epidemiology of this pathogen, new approaches are needed for effective management. In 1984, Dr Barry Marshall and Dr Robin Warren reported the association of Helicobacter pylori with peptic ulcers in The Lancet—a discovery that earned them the Nobel prize in Physiology or Medicine in 2005—but what progress have we made since then? Here, we have invited three international experts to give their insights into the advances in H. pylori research over the past 30 years and where research should be focused in the future. PMID:23752823
López Pérez, Gerardo; Alcántara Rodríguez, Fernando
The rise in the incidence of atopic diseases in the last years is associated to a greater prevalence of viral and bacterial infections. The infections facilitate a chronic inflammatory process that is directly related to the sensibilization of mast cells which favors manifestations of allergic diseases. Within the proposed bacteriological agents as causes of is Helicobacter pylori. This work is a bibliographical revision and concludes that there is not evidence of the direct causal relation between infection by Helicobacter and allergic diseases; however, it can play an indirect role. Controlled and randomized studies are necessary to know accurately this relation because the eradication treatment could be a real alternative in these patients handling.
Helicobacter pylori (HP) is a common infection of the gastrointestinal system that is usually related to peptic ulcers. However, recent studies have revealed relationships between HP and many other diseases. Although the exact mechanism is unknown, HP can prevent the absorption of certain drugs. A high prevalence of HP has been found in patients with Parkinson's disease, and this bacterium causes motor fluctuations by affecting the absorption of levodopa, which is the main drug used to treat Parkinson's disease. Eradicating HP from patients with Parkinson's disease by applying antibiotic treatment will increase the absorption of levodopa and decrease their motor fluctuations. PMID:26932258
Bin Mohanna, Mabrook A; Al-Zubairi, Lutf M; Sallam, Abdul K
To estimate the prevalence of Helicobacter pylori (H. pylori) and parasites in symptomatic children examined for H. pylori antibodies, antigens, and parasites in Yemen. A record-based study was carried out at Specialized Sam Pediatric Center in Sana'a, Yemen for 3 years between 2011-2013. Out of the 43,200 patients seen for different causes through that period, 1008 (2.3%) (females: 675 [67%]; males: 333 [33%]) had gastric complaints, and were subjected to an examination of blood and stool for H. pylori and parasites. Data regarding age and gender was also collected. The age of the patients ranged from 3-15 years. The prevalence of H. pylori among children examined for H. pylori was 65%, 30% of them were males, and 35% were females (chi square [I2]=142, p<0.01]). The prevalence in the 6-8 years age group was 83%, and it was 52% in the age group of 12-15 years. The prevalence of giardiasis was 10%, and amoebiasis was 25%. Prevalence of H. pylori infection among children was high, and was more prevalent in the age group of 6-8 years than in the other age groups. Females were more affected than males. Parasites (amoebiasis and giardiasis) infestation was less prevalent.
Ulas, Turgay; Tursun, Irfan; Dal, Mehmet Sinan; Eren, Mehmet Ali; Buyukhatipoglu, Hakan
Helicobacter pylori (H. pylori) are one of the most common bacterial infections, seen in humans, worldwide and their possible relationships to different diseases are a focus of attention nowadays. H. pylori may cause some extra intestinal manifestations some of which are dermatological conditions, including Henoch-Schönlein purpura (HSP), chronic urticaria and atopic dermatitis. We describe a 49-year-old man who presented with HSP triggered by gastric H. pylori infection. Treatment of H. Pylori infection was accompanied by prompt resolution of the gastrointestinal manifestations and purpuric rashes. These findings suggest a causative role for H. pylori in the occurrence of HSP. PMID:23833587
Nagasawa, Sayaka; Azuma, Takeshi; Motani, Hisako; Sato, Yayoi; Hayakawa, Mutsumi; Yajima, Daisuke; Kobayashi, Kazuhiro; Ootsuka, Katsura; Iwase, Hirotaro
It is thought that there is a close relationship between regionality and DNA polymorphism of H.pylori. The application of H.pylori DNA to estimate the origin of unidentified cadavers may be possible. Previously, we detected H.pylori DNA in five stomach lesions by PCR in 50% of 100 cadavers in forensic autopsies. Furthermore, to see the localization of H.pylori in the digestive system, we tried to assay H.pylori DNA by real-time PCR. Mucous membranes at 14 points of digestive systems (5 points of the stomach, 1 point of the duodenum, 5 points of the small intestine, 3 points of the large intestine) were obtained from three cadavers whose stools were H.pylori-positive by an ImmunoCardST!HpSA detection kit. Genomic DNA was extracted using a DNA extraction kit. The 23Sr-DNA region was PCR-amplified (320 bp) by a TOYOBO Kit and the same region was assayed by real-time PCR using a Taqman probe. The PCR products were detected in 5 points of the stomach and 1 point of the duodenum in each sample. The more peripheral the intestine lesion was the weaker the band became. The quantitative PCR showed that there were more PCR products in 5 points of the stomach and 1 point of the duodenum than in the other tissues. H.pylori DNA was detected not only in the stomach but also in the duodenum and small intestine. There was a difference in the amount of H.pylori DNA detected in each organ. Further study is required for immunohistochemical staining, and to determine the relationship between a persons natural state and the H.pylori DNA polymorphism (which codes for CagA).
Sachdeva, Aarti; Rawat, Swapnil; Nagpal, Jitender
Helicobacter pylori (H. pylori) eradication is considered a necessary step in the management of peptic ulcer disease, chronic gastritis, gastric adenocarcinoma and mucosa associated lymphoid tissue lymphoma. Standard triple therapy eradication regimens are inconvenient and achieve unpredictable and often poor results. Eradication rates are decreasing over time with increase in antibiotic resistance. Fermented milk and several of its component whey proteins have emerged as candidates for complementary therapy. In this context the current review seeks to summarize the current evidence available on their role in H. pylori eradication. Pertinent narrative/systematic reviews, clinical trials and laboratory studies on individual components including fermented milk, yogurt, whey proteins, lactoferrin, α-lactalbumin (α-LA), glycomacropeptide and immunoglobulin were comprehensively searched and retrieved from Medline, Embase, Scopus, Cochrane Controlled Trials Register and abstracts/proceedings of conferences up to May 2013. A preponderance of the evidence available on fermented milk-based probiotic preparations and bovine lactoferrin suggests a beneficial effect in Helicobacter eradication. Evidence for α-LA and immunoglobulins is promising while that for glycomacropeptide is preliminary and requires substantiation. The magnitude of the potential benefit documented so far is small and the precise clinical settings are ill defined. This restricts the potential use of this group as a complementary therapy in a nutraceutical setting hinging on better patient acceptability/compliance. Further work is necessary to identify the optimal substrate, fermentation process, dose and the ideal clinical setting (prevention/treatment, first line therapy/recurrence, symptomatic/asymptomatic, gastritis/ulcer diseases etc.). The potential of this group in high antibiotic resistance or treatment failure settings presents interesting possibilities and deserves further exploration.
Sachdeva, Aarti; Rawat, Swapnil; Nagpal, Jitender
Helicobacter pylori (H. pylori) eradication is considered a necessary step in the management of peptic ulcer disease, chronic gastritis, gastric adenocarcinoma and mucosa associated lymphoid tissue lymphoma. Standard triple therapy eradication regimens are inconvenient and achieve unpredictable and often poor results. Eradication rates are decreasing over time with increase in antibiotic resistance. Fermented milk and several of its component whey proteins have emerged as candidates for complementary therapy. In this context the current review seeks to summarize the current evidence available on their role in H. pylori eradication. Pertinent narrative/systematic reviews, clinical trials and laboratory studies on individual components including fermented milk, yogurt, whey proteins, lactoferrin, α-lactalbumin (α-LA), glycomacropeptide and immunoglobulin were comprehensively searched and retrieved from Medline, Embase, Scopus, Cochrane Controlled Trials Register and abstracts/proceedings of conferences up to May 2013. A preponderance of the evidence available on fermented milk-based probiotic preparations and bovine lactoferrin suggests a beneficial effect in Helicobacter eradication. Evidence for α-LA and immunoglobulins is promising while that for glycomacropeptide is preliminary and requires substantiation. The magnitude of the potential benefit documented so far is small and the precise clinical settings are ill defined. This restricts the potential use of this group as a complementary therapy in a nutraceutical setting hinging on better patient acceptability/compliance. Further work is necessary to identify the optimal substrate, fermentation process, dose and the ideal clinical setting (prevention/treatment, first line therapy/recurrence, symptomatic/asymptomatic, gastritis/ulcer diseases etc.). The potential of this group in high antibiotic resistance or treatment failure settings presents interesting possibilities and deserves further exploration. PMID
Dixon, Beverly R. E. A.; Radin, Jana N.; Piazuelo, M. Blanca; Contreras, Diana C.; Algood, Holly M. Scott
Helicobacter pylori colonization of the human stomach can lead to adverse clinical outcomes including gastritis, peptic ulcers, or gastric cancer. Current data suggest that in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonization. Specifically, CD4+ T cell responses impact the pathology elicited in response to H. pylori. Because gastritis is believed to be the initiating host response to more detrimental pathological outcomes, there has been a significant interest in pro-inflammatory T cell cytokines, including the cytokines produced by T helper 17 cells. Th17 cells produce IL-17A, IL-17F, IL-21 and IL-22. While these cytokines have been linked to inflammation, IL-17A and IL-22 are also associated with anti-microbial responses and control of bacterial colonization. The goal of this research was to determine the role of IL-22 in activation of antimicrobial responses in models of H. pylori infection using human gastric epithelial cell lines and the mouse model of H. pylori infection. Our data indicate that IL-17A and IL-22 work synergistically to induce antimicrobials and chemokines such as IL-8, components of calprotectin (CP), lipocalin (LCN) and some β-defensins in both human and primary mouse gastric epithelial cells (GEC) and gastroids. Moreover, IL-22 and IL-17A-activated GECs were capable of inhibiting growth of H. pylori in vitro. While antimicrobials were activated by IL-17A and IL-22 in vitro, using a mouse model of H. pylori infection, the data herein indicate that IL-22 deficiency alone does not render mice more susceptible to infection, change their antimicrobial gene transcription, or significantly change their inflammatory response. PMID:26867135
Correa, P; Piazuelo, M B
This report describes the modalities of chronic gastritis induced by Helicobacter pylori infection in different populations. The full gamut of lesions representing the precancerous cascade is very prevalent in populations of low socioeconomic background experiencing very high gastric cancer risk, as seen in the Latin American Andes Mountains. In populations of high socioeconomic standards and high cancer risk, such as Japan and Korea, the precancerous cascade predominates and "early" cancers are also diagnosed frequently. Some reports describe frequent corpus atrophy, not prominent in the former group. The so-called African enigma is seen in populations of low socioeconomic standards, usually living at low altitudes, with high prevalence of infection but low frequency of cancer and precancerous lesions. In populations in transition from high to low cancer risk, duodenal ulcer and antral non-atrophic gastritis are frequently seen. In affluent societies at low risk of cancer, such as Western Europe, Australia and North America, mild non-atrophic gastritis associated with low virulence Helicobacter pylori genotypes predominate. The varied phenotypes of gastritis may reflect secular changes in the ecology of our species.
Rivas, F; Rivera, P; Hernández, F; Hevia, F; Guillén, F; Tamayo, G
The gastric pathogen Helicobacter pylori has been recognized as the major aetiologic agent of chronic gastritis and peptic ulcers and also a risk factor for gastric cancer; eradication of H pylori prevents peptic ulcer recurrence and may also decrease the prevalence of gastric cancer in high risk populations around the world. Currently the only accepted indication for treatment is ulcer disease and maltosa, infected with Helicobacter pilory. However treatment is difficult and easily develops resistance. The elaboration of an antibiotic profile is recommended after a treatment failure. There is a lack of information in developing countries so the aim of this work was to determine the antibiotic profile of 51 strains isolated from patients gastric biopsies attended at Hospital San Juan de Dios in Costa Rica, using egg yolk broth and finding a resistance of 63.0% to metronidazole with a breakpoint of 8.0 microg/ml and 20.0% resistance to tetracycline (MIC1.0 microg/ml), 6.0% to clarithromicyn with a MIC of 0.125 microg/ml. There was no resistance to amoxicilin (MIC 0.015 microg/ml). The microdilution technique is very laborious, but highly reproducible with results accordingly to previous work, and we recommended it for the designing of therapeutical scheme.
Atherton, John C.; Blaser, Martin J.
Humans have been colonized by Helicobacter pylori for at least 50,000 years and probably throughout their evolution. H. pylori has adapted to humans, colonizing children and persisting throughout life. Most strains possess factors that subtly modulate the host environment, increasing the risk of peptic ulceration, gastric adenocarcinoma, and possibly other diseases. H. pylori genes encoding these and other factors rapidly evolve through mutation and recombination, changing the bacteria-host interaction. Although immune and physiologic responses to H. pylori also contribute to pathogenesis, humans have evolved in concert with the bacterium, and its recent absence throughout the life of many individuals has led to new human physiological changes. These may have contributed to recent increases in esophageal adenocarcinoma and, more speculatively, other modern diseases. PMID:19729845
NCI supported research to solidify the link between H. pylori infections and stomach cancer. As a result, new cancer treatment and prevention strategies are being developed, encouraging scientists to carefully examine other cancers for viral and bacterial connections.
Sarem, Muhannad; Corti, Rodolfo
Helicobacter pylori is a spiral Gram-negative bacillus, which colonizes the human stomach and plays a key role in the pathogenesis of a number of gastroduodenal diseases. However, when expose to environmental stressed conditions, such as increased oxygen tension, extended incubation and exposure to antibiotics, Helicobacter pylori is able to entering the viable but nonculturable state, in which the bacterium modifies its morphology from a spiral to coccoid form, as a manifestation of cell adaptation to these adverse conditions. In gastric tissues, viable coccoid forms may remain latent for long time and retain virulence factors, so these forms possibly contribute to the treatment failures and recurrence of Helicobacter pylori infection and gastroduodenal diseases as well. In this review, we will discuss several aspects of cellular adaptation and survival of Helicobacter pylori, antibiotic susceptibility and virulence of coccoid forms and its involvement with recrudescence. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.
Fernandes, Ricardo M; Silva, Hélder; Oliveira, Ricardo; Almeida, Carina; Azevedo, Nuno F; Vieira, Maria J
This study aims to investigate the morphological transition of Helicobacter pylori during adaptation to water. Different strains were adapted to water. Changes regarding cultivability and cellular morphology were recorded. Expression of 11 genes involved in H. pylori morphological changes was evaluated by real-time PCR. H. pylori presented increased cultivability in water after adaptation. The permanent loss of the spiral shape was observed, but no transition into coccoid form has occurred. Expression levels of genes involved in peptidoglycan assembly of H. pylori 26695 have shown significant changes between adapted and nonadapted strains. Adaption to water favors the culturable phenotype and the morphological transition to the rod shape, into a process that implicates the peptidoglycan turnover.
AlMalki, Ahmad S.
One-half of the world's population has Helicobacter pylori (H. pylori) infection while dyspeptic symptoms affect one-third of the adult population, at least in the Western world. Data from epidemiological studies are controversial in terms of the association of H. pylori with non-ulcer dyspepsia (NUD) symptoms. Despite the frequency of occurrence of this clinical condition, no effective therapy exists in treating this disorder. With the strategic aim of treating NUD, a vast amount of evidence has accumulated towards eradicating H. pylori, while an equally compelling amount of evidence exists that counters this very strategy. It is, therefore, vital that there is reliable evidence for the efficacy of treatments prescribed to NUD patients. The arguments for and against the eradication of this organism continues unabated. We aim to address both sides of this fundamental divide and present the differing perspective in light of the prevalent evidence. PMID:19568510
Matsuo, Yuichi; Kido, Yasutoshi; Yamaoka, Yoshio
Helicobacter pylori colonizes the human stomach and induces inflammation, and in some cases persistent infection can result in gastric cancer. Attachment to the gastric mucosa is the first step in establishing bacterial colonization, and outer membrane proteins (OMPs) play a pivotal role in binding to human cells. Some OMP interaction molecules are known in H. pylori, and their associated host cell responses have been gradually clarified. Many studies have demonstrated that OMPs are essential to CagA translocation into gastric cells via the Type IV secretion system of H. pylori. This review summarizes the mechanisms through which H. pylori utilizes OMPs to colonize the human stomach and how OMPs cooperate with the Type IV secretion system. PMID:28287480
Sheh, Alexander; Fox, James G
The discovery of Helicobacter pylori overturned the conventional dogma that the stomach was a sterile organ and that pH values < 4 were capable of sterilizing the stomach. H. pylori are an etiological agent associated with gastritis, hypochlorhydria, duodenal ulcers, and gastric cancer. It is now appreciated that the human stomach supports a bacterial community with possibly 100s of bacterial species that influence stomach homeostasis. Other bacteria colonizing the stomach may also influence H. pylori-associated gastric pathogenesis by creating reactive oxygen and nitrogen species and modulating inflammatory responses. In this review, we summarize the available literature concerning the gastric microbiota in humans, mice, and Mongolian gerbils. We also discuss the gastric perturbations, many involving H. pylori, that facilitate the colonization by bacteria from other compartments of the gastrointestinal tract, and identify risk factors known to affect gastric homeostasis that contribute to changes in the microbiota. PMID:23962822
Sheh, Alexander; Fox, James G
The discovery of Helicobacter pylori overturned the conventional dogma that the stomach was a sterile organ and that pH values<4 were capable of sterilizing the stomach. H. pylori are an etiological agent associated with gastritis, hypochlorhydria, duodenal ulcers, and gastric cancer. It is now appreciated that the human stomach supports a bacterial community with possibly 100s of bacterial species that influence stomach homeostasis. Other bacteria colonizing the stomach may also influence H. pylori-associated gastric pathogenesis by creating reactive oxygen and nitrogen species and modulating inflammatory responses. In this review, we summarize the available literature concerning the gastric microbiota in humans, mice, and Mongolian gerbils. We also discuss the gastric perturbations, many involving H. pylori, that facilitate the colonization by bacteria from other compartments of the gastrointestinal tract, and identify risk factors known to affect gastric homeostasis that contribute to changes in the microbiota.
Matsuo, Yuichi; Kido, Yasutoshi; Yamaoka, Yoshio
Helicobacter pylori colonizes the human stomach and induces inflammation, and in some cases persistent infection can result in gastric cancer. Attachment to the gastric mucosa is the first step in establishing bacterial colonization, and outer membrane proteins (OMPs) play a pivotal role in binding to human cells. Some OMP interaction molecules are known in H. pylori, and their associated host cell responses have been gradually clarified. Many studies have demonstrated that OMPs are essential to CagA translocation into gastric cells via the Type IV secretion system of H. pylori. This review summarizes the mechanisms through which H. pylori utilizes OMPs to colonize the human stomach and how OMPs cooperate with the Type IV secretion system.
Goddard, A F; Logan, R P H
Helicobacter pylori is the principal cause of peptic ulcer disease and an important risk factor for the development of gastric cancer. The efficacy of 1 week triple therapies, which often have eradication rates of > 90%, is undermined by poor patient compliance and bacterial antimicrobial resistance. The development of new anti-H. pylori therapies presents enormous challenges to clinical pharmacologists, not only in the identification of novel targets, but also in ensuring adequate drug delivery to the unique gastric mucus niche of H. pylori. Animal models of H. pylori infection have been developed but their clinical validity has yet to be established. Vaccination, to prevent or treat infection, has been demonstrated in animal models, but human studies have not been so encouraging. PMID:12919175
Keenan, Jacqueline I; Salm, Nina; Hampton, Mark B; Wallace, Alison J
Eradication of H. pylori can reduce the risk of non-cardia gastric cancer developing in infected humans. Thus, the consumption of foods that inhibit the growth of these bacteria may provide an alternative to current therapies that include antibiotics, proton pump inhibitors and/or bismuth salts. This study describes a simple broth dilution assay developed to screen a range of foods for their individual and combined effects on H. pylori growth. It was found that foods with measurable anti-H. pylori activity have an effect greater in combination than the sum of foods tested singly, and that this was most noticeable with a combination of broccoli sprouts and blackcurrant oil. The results suggest that food synergy should be considered in any nutraceutical approach to H. pylori infection.
Arnold, Donald M.; Bernotas, Ashley; Nazi, Ishac; Stasi, Roberto; Kuwana, Masataka; Liu, Yang; Kelton, John G.; Crowther, Mark A.
Eradication of H. pylori improves thrombocytopenia in some patients with immune thrombocytopenic purpura by mechanisms that remain obscure. Platelet count responses may occur independently of H. pylori infection as a result of the immune modulating effects of macrolide antimicrobials or the removal of other commensal bacteria. We performed a systematic review of the literature to determine the effect of H. pylori eradication therapy in patients with immune thrombocytopenic purpura by comparing the platelet response in patients who were, and who were not infected with H. pylori. MEDLINE, EMBASE, Cochrane central registry and abstracts from the American Society of Hematology (from 2003) were searched in duplicate and independently without language or age restrictions. Eleven studies, 8 from Japan, were included enrolling 282 patients with immune thrombocytopenic purpura who received eradication therapy; 205 were H. pylori-positive and 77 were H. pylori-negative. The odds of achieving a platelet count response following eradication therapy were 14.5 higher (95% confidence interval 4.2 to 83.0) in patients with H. pylori infection (51.2% vs. 8.8%). No study reported bleeding or quality of life. Adverse events were reported in 12 patients. H. pylori eradication therapy was of little benefit for H. pylori-negative patients. These findings strengthen the causal association between H. pylori infection and immune thrombocytopenia in some patients. Randomized trials are needed to determine the applicability of H. pylori eradication therapy across diverse geographical regions. PMID:19483158
Saijo, Yasuaki; Yoshioka, Eiji; Fukui, Tomonori; Kawaharada, Mariko; Sata, Fumihiro; Sato, Hirokazu; Kishi, Reiko
AIM: To investigate whether the pro- and anti-inflammatory cytokine gene polymorphisms, IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G, interact with smoking and drinking habits to influence infection with H pylori. METHODS: The subjects were 410 Japanese transit company employees. C-reactive protein and conventional cardiovascular risk factors were evaluated. Serum anti-H pylori antibodies were measured. The genotypes of IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G polymorphisms were determined by allelic discrimination using fluorogenic probes and a 5´nuclease assay. RESULTS: In gender- and age-adjusted logistic analyses, the subjects with TNF-857T/T had a significantly lower odds ratio (OR) for H pylori seropositivity (reference -857C/C; OR = 0.15, 95%CI: 0.03-0.59, P = 0.007). After stratification according to smoking and drinking status, among never-smokers, the subjects with IL1B-511C/T had a significantly lower OR (reference -511C/C; OR = 0.30, 95%CI: 0.10-0.90, P = 0.032). Among drinkers in the 1-5 times/wk category, the subjects with IL1B-511T/T had a significantly lower OR (reference C/C; OR = 0.38, 95%CI: 0.16-0.95, P = 0.039), and the subjects with IL1B-31C/T and T/T had a significantly higher OR (reference C/C; C/T: OR = 2.59, 95%CI, P = 0.042: 1.04-6.47; C/C: OR = 3.17, 95%CI: 1.23-8.14, P = 0.017). Among current smokers, the subjects with IL6-634C/G had a significantly higher OR (reference C/C; OR = 2.28, 95%CI: 1.13-4.58, P = 0.021). However, the interactions terms between the aforementioned genotypes and lifestyles were not statistically significant. CONCLUSION: Contrary to previous findings, the results herein suggest that the TNF-857T/T genotype may be protective against chronic infection with H pylori. Drinking and smoking habits may influence the effect of cytokine gene polymorphisms. Further studies are required to clarify the effects of the pro- and anti-inflammatory cytokine
Perry, Sharon; de Jong, Bouke C.; Solnick, Jay V.; la Luz Sanchez, Maria de; Yang, Shufang; Lin, Philana Ling; Hansen, Lori M.; Talat, Najeeha; Hill, Philip C.; Hussain, Rabia; Adegbola, Richard A.; Flynn, JoAnne; Canfield, Don; Parsonnet, Julie
Background Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis. Methodology/Principal Findings We first examined M. tuberculosis-specific IFN-γ and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29%) meeting criteria for latent tuberculosis (TB) infection (LTBI), 45 (46%) were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-γ responses (p = 0.04, ANOVA), and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36–0.83, p = 0.005), though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63–2.9] p = 0.44). Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12–0.80], p = 0.04). Conclusions/Significance H. pylori infection may induce bystander effects that modify the risk of active TB in humans and non-human primates. That immunity to TB may be enhanced by exposure to other microbial agents may have important implications for
Montano, Valeria; Maady, Ayas; Nkwescheu, Armand; Siri, Jose; Elamin, Wael F.; Falush, Daniel; Linz, Bodo; Achtman, Mark; Moodley, Yoshan; Suerbaum, Sebastian
Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the d