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Fuchs S, Fiedler MK, Heiduk N, Wanisch A, Mibus C, Singh D, Debowski AW, Marshall BJ, Vieth M, Josenhans C, Suerbaum S, Sieber SA, Gerhard M, Mejías-Luque R. Helicobacter pylori γ-glutamyltransferase is linked to proteomic adaptions important for colonization. Gut Microbes 2025; 17:2488048. [PMID: 40205659 PMCID: PMC11988274 DOI: 10.1080/19490976.2025.2488048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 03/18/2025] [Accepted: 03/28/2025] [Indexed: 04/11/2025] Open
Abstract
Helicobacter pylori γ-glutamyltransferase (gGT) is a virulence factor that promotes bacterial colonization and immune tolerance. Although some studies addressed potential functional mechanisms, the supportive role of gGT for in vivo colonization remains unclear. Additionally, it is unknown how different gGT expression levels may lead to compensatory mechanisms ensuring infection and persistence. Hence, it is crucial to unravel the in vivo function of gGT. We assessed acid survival under conditions mimicking the human gastric fluid and elevated the pH in the murine stomach prior to H. pylori infection to link gGT-mediated acid resistance to colonization. By comparing proteomes of gGT-proficient and -deficient isolates before and after infecting mice, we investigated proteomic adaptations of gGT-deficient bacteria during infection. Our data indicate that gGT is crucial to sustain urease activity in acidic environments, thereby supporting survival and successful colonization. Absence of gGT triggers expression of proteins involved in the nitrogen and iron metabolism and boosts the expression of adhesins and flagellar proteins during infection, resulting in increased motility and adhesion capacity. In summary, gGT-dependent mechanisms confer a growth advantage to the bacterium in the gastric environment, which renders gGT a valuable target for the development of new treatments against H. pylori infection.
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Affiliation(s)
- Sonja Fuchs
- Institute for Medical Microbiology, Immunology and Hygiene, Department of Preclinical Medicine, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany
| | - Michaela K. Fiedler
- Center for Functional Protein Assemblies (CPA), Chair of Organic Chemistry II, Department Biosciences, TUM School of Natural Sciences, Technical University of Munich (TUM), Garching, Germany
| | - Nicole Heiduk
- Institute for Medical Microbiology, Immunology and Hygiene, Department of Preclinical Medicine, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany
| | - Andreas Wanisch
- Institute for Medical Microbiology, Immunology and Hygiene, Department of Preclinical Medicine, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany
| | - Cora Mibus
- Institute for Medical Microbiology, Immunology and Hygiene, Department of Preclinical Medicine, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany
| | - Dharmesh Singh
- Institute for Medical Microbiology, Immunology and Hygiene, Department of Preclinical Medicine, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany
| | - Aleksandra W. Debowski
- Marshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, The University of Western Australia, Nedlands, Australia
- School of Molecular Sciences, The University of Western Australia, Crawley, Australia
| | - Barry J. Marshall
- Marshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, The University of Western Australia, Nedlands, Australia
| | - Michael Vieth
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg, Klinikum Bayreuth, Bayreuth, Germany
| | - Christine Josenhans
- Max von Pettenkofer Institute, Faculty of Medicine, Medical Microbiology and Hospital Epidemiology, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- DZIF - German Center for Infection Research, Partner Site Munich, Munich, Germany
| | - Sebastian Suerbaum
- Max von Pettenkofer Institute, Faculty of Medicine, Medical Microbiology and Hospital Epidemiology, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- DZIF - German Center for Infection Research, Partner Site Munich, Munich, Germany
| | - Stephan A. Sieber
- Center for Functional Protein Assemblies (CPA), Chair of Organic Chemistry II, Department Biosciences, TUM School of Natural Sciences, Technical University of Munich (TUM), Garching, Germany
| | - Markus Gerhard
- Institute for Medical Microbiology, Immunology and Hygiene, Department of Preclinical Medicine, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany
| | - Raquel Mejías-Luque
- Institute for Medical Microbiology, Immunology and Hygiene, Department of Preclinical Medicine, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany
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Krzysiek-Maczka G, Brzozowski T, Ptak-Belowska A. Helicobacter pylori-activated fibroblasts as a silent partner in gastric cancer development. Cancer Metastasis Rev 2023; 42:1219-1256. [PMID: 37460910 PMCID: PMC10713772 DOI: 10.1007/s10555-023-10122-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 06/20/2023] [Indexed: 12/18/2023]
Abstract
The discovery of Helicobacter pylori (Hp) infection of gastric mucosa leading to active chronic gastritis, gastroduodenal ulcers, and MALT lymphoma laid the groundwork for understanding of the general relationship between chronic infection, inflammation, and cancer. Nevertheless, this sequence of events is still far from full understanding with new players and mediators being constantly identified. Originally, the Hp virulence factors affecting mainly gastric epithelium were proposed to contribute considerably to gastric inflammation, ulceration, and cancer. Furthermore, it has been shown that Hp possesses the ability to penetrate the mucus layer and directly interact with stroma components including fibroblasts and myofibroblasts. These cells, which are the source of biophysical and biochemical signals providing the proper balance between cell proliferation and differentiation within gastric epithelial stem cell compartment, when exposed to Hp, can convert into cancer-associated fibroblast (CAF) phenotype. The crosstalk between fibroblasts and myofibroblasts with gastric epithelial cells including stem/progenitor cell niche involves several pathways mediated by non-coding RNAs, Wnt, BMP, TGF-β, and Notch signaling ligands. The current review concentrates on the consequences of Hp-induced increase in gastric fibroblast and myofibroblast number, and their activation towards CAFs with the emphasis to the altered communication between mesenchymal and epithelial cell compartment, which may lead to inflammation, epithelial stem cell overproliferation, disturbed differentiation, and gradual gastric cancer development. Thus, Hp-activated fibroblasts may constitute the target for anti-cancer treatment and, importantly, for the pharmacotherapies diminishing their activation particularly at the early stages of Hp infection.
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Affiliation(s)
- Gracjana Krzysiek-Maczka
- Department of Physiology, the Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Kraków, Poland.
| | - Tomasz Brzozowski
- Department of Physiology, the Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Kraków, Poland.
| | - Agata Ptak-Belowska
- Department of Physiology, the Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Kraków, Poland
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Bonsor DA, Sundberg EJ. Roles of Adhesion to Epithelial Cells in Gastric Colonization by Helicobacter pylori. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1149:57-75. [PMID: 31016628 DOI: 10.1007/5584_2019_359] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori adherence to host epithelial cells is essential for its survival against the harsh conditions of the stomach and for successful colonization. Adherence of H. pylori is achieved through several related families of outer membrane proteins and proteins of a type IV secretion system (T4SS), which bridge H. pylori to host cells through protein-protein and other protein-ligand interactions. Local environmental conditions such as cell type, available host cell surface proteins and/or ligands, as well as responses by the host immune system force H. pylori to alter expression of these proteins to adapt quickly to the local environment in order to colonize and survive. Some of these host-pathogen interactions appear to function in a "catch-and-release" manner, regulated by reversible binding at varying pH and allowing H. pylori to detach itself from cells or debris sloughed off the gastric epithelial lining in order to return for subsequent productive interactions. Other interactions between bacterial adhesin proteins and host adhesion molecules, however, appear to function as a committed step in certain pathogenic processes, such as translocation of the CagA oncoprotein through the H. pylori T4SS and into host gastric epithelial cells. Understanding these adhesion interactions is critical for devising new therapeutic strategies, as they are responsible for the earliest stage of infection and its maintenance. This review will discuss the expression and regulation of several outer membrane proteins and CagL, how they engage their known host cell protein/ligand targets, and their effects on clinical outcome.
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Affiliation(s)
- Daniel A Bonsor
- Institute of Human Virology, University of Maryland School of Medicine, University of Maryland, Baltimore, MD, USA
| | - Eric J Sundberg
- Institute of Human Virology, University of Maryland School of Medicine, University of Maryland, Baltimore, MD, USA. .,Department of Medicine, University of Maryland School of Medicine, University of Maryland, Baltimore, MD, USA. .,Department of Microbiology and Immunology, University of Maryland School of Medicine, University of Maryland, Baltimore, MD, USA.
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Padra M, Adamczyk B, Benktander J, Flahou B, Skoog EC, Padra JT, Smet A, Jin C, Ducatelle R, Samuelsson T, Haesebrouck F, Karlsson NG, Teneberg S, Lindén SK. Helicobacter suis binding to carbohydrates on human and porcine gastric mucins and glycolipids occurs via two modes. Virulence 2018; 9:898-918. [PMID: 29638186 PMCID: PMC5955484 DOI: 10.1080/21505594.2018.1460979] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Helicobacter suis colonizes the stomach of most pigs and is the most prevalent non-Helicobacter pylori Helicobacter species found in the human stomach. In the human host, H. suis contributes to the development of chronic gastritis, peptic ulcer disease and MALT lymphoma, whereas in pigs it is associated with gastritis, decreased growth and ulcers. Here, we demonstrate that the level of H. pylori and H. suis binding to human and pig gastric mucins varies between individuals with species dependent specificity. The binding optimum of H. pylori is at neutral pH whereas that of H. suis has an acidic pH optimum, and the mucins that H. pylori bind to are different than those that H. suis bind to. Mass spectrometric analysis of mucin O-glycans from the porcine mucin showed that individual variation in binding is reflected by a difference in glycosylation; of 109 oligosaccharide structures identified, only 14 were present in all examined samples. H. suis binding to mucins correlated with glycans containing sulfate, sialic acid and terminal galactose. Among the glycolipids present in pig stomach, binding to lactotetraosylceramide (Galβ3GlcNAcβ3Galβ4Glcβ1Cer) was identified, and adhesion to Galβ3GlcNAcβ3Galβ4Glc at both acidic and neutral pH was confirmed using other glycoconjugates. Together with that H. suis bound to DNA (used as a proxy for acidic charge), we conclude that H. suis has two binding modes: one to glycans terminating with Galβ3GlcNAc, and one to negatively charged structures. Identification of the glycan structures H. suis interacts with can contribute to development of therapeutic strategies alternative to antibiotics.
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Affiliation(s)
- Médea Padra
- a Department of Medical Biochemistry and Cell Biology , Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - Barbara Adamczyk
- a Department of Medical Biochemistry and Cell Biology , Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - John Benktander
- a Department of Medical Biochemistry and Cell Biology , Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - Bram Flahou
- b Department of Pathology , Bacteriology and Avian Diseases, Ghent University , Belgium
| | - Emma C Skoog
- a Department of Medical Biochemistry and Cell Biology , Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - János Tamás Padra
- a Department of Medical Biochemistry and Cell Biology , Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - Annemieke Smet
- b Department of Pathology , Bacteriology and Avian Diseases, Ghent University , Belgium.,c Laboratorium of Experimental Medicine and Pediatrics , Faculty of Medicine and Health Sciences, University of Antwerp , Antwerp
| | - Chunsheng Jin
- a Department of Medical Biochemistry and Cell Biology , Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - Richard Ducatelle
- b Department of Pathology , Bacteriology and Avian Diseases, Ghent University , Belgium
| | - Tore Samuelsson
- a Department of Medical Biochemistry and Cell Biology , Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - Freddy Haesebrouck
- b Department of Pathology , Bacteriology and Avian Diseases, Ghent University , Belgium
| | - Niclas G Karlsson
- a Department of Medical Biochemistry and Cell Biology , Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - Susann Teneberg
- a Department of Medical Biochemistry and Cell Biology , Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - Sara K Lindén
- a Department of Medical Biochemistry and Cell Biology , Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
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Gutiérrez-Escobar AJ, Trujillo E, Acevedo O, Bravo MM. Phylogenomics of Colombian Helicobacter pylori isolates. Gut Pathog 2017; 9:52. [PMID: 28912838 PMCID: PMC5594506 DOI: 10.1186/s13099-017-0201-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Accepted: 09/03/2017] [Indexed: 12/27/2022] Open
Abstract
Background 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. Results 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. Conclusions 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. Electronic supplementary material The online version of this article (doi:10.1186/s13099-017-0201-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Andrés Julián Gutiérrez-Escobar
- Grupo de Investigaciones Biomédicas y Genética Humana Aplicada, Programa de Medicina, Universidad de Ciencias Aplicadas y Ambientales, Calle 222 55-37, Bogotá, Colombia.,Programa de Doctorado en Ciencias Biológicas, Universidad Javeriana, Carrera 7 40-62, Bogotá, Colombia
| | - Esperanza Trujillo
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Calle 1 9-85, Bogotá, Colombia
| | - Orlando Acevedo
- Grupo de Biofísica y Bioquímica Estructural, Facultad de Ciencias, Pontificia Universidad Javeriana, Carrera 7 40-62, Bogotá, Colombia
| | - María Mercedes Bravo
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Calle 1 9-85, Bogotá, Colombia
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Chmiela M, Karwowska Z, Gonciarz W, Allushi B, Stączek P. Host pathogen interactions in Helicobacter pylori related gastric cancer. World J Gastroenterol 2017; 23:1521-1540. [PMID: 28321154 PMCID: PMC5340805 DOI: 10.3748/wjg.v23.i9.1521] [Citation(s) in RCA: 89] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Revised: 10/26/2016] [Accepted: 02/16/2017] [Indexed: 02/06/2023] Open
Abstract
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.
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Vannini A, Roncarati D, Danielli A. The cag-pathogenicity island encoded CncR1 sRNA oppositely modulates Helicobacter pylori motility and adhesion to host cells. Cell Mol Life Sci 2016; 73:3151-68. [PMID: 26863876 PMCID: PMC11108448 DOI: 10.1007/s00018-016-2151-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2015] [Revised: 01/13/2016] [Accepted: 01/28/2016] [Indexed: 02/08/2023]
Abstract
Small regulatory RNAs (sRNAs) are emerging as key post-transcriptional regulators in many bacteria. In the human pathobiont Helicobacter pylori a plethora of trans- and cis-encoded sRNAs have been pinpointed by a global transcriptome study. However, only two have been studied in depth at the functional level. Here we report the characterization of CncR1, an abundant and conserved sRNA encoded by the virulence-associated cag pathogenicity island (cag-PAI) of H. pylori. Growth-phase dependent transcription of CncR1 is directed by the PcagP promoter, which resulted to be a target of the essential transcriptional regulator HsrA (HP1043). We demonstrate that the 213 nt transcript arising from this promoter ends at an intrinsic terminator, few bases upstream of the annotated cagP open reading frame, establishing CncR1 as the predominant gene product encoded by the cagP (cag15) locus. Interestingly, the deletion of the locus resulted in the deregulation en masse of σ(54)-dependent genes, linking CncR1 to flagellar functions. Accordingly, the enhanced motility recorded for cncR1 deletion mutants was complemented by ectopic reintroduction of the allele in trans. In silico prediction identified fliK, encoding a flagellar checkpoint protein, as likely regulatory target of CncR1. The interaction of CncR1 with the fliK mRNA was thus further investigated in vitro, demonstrating the formation of strand-specific interactions between the two RNA molecules. Accordingly, the full-length translational fusions of fliK with a lux reporter gene were induced in a cncR1 deletion mutant in vivo. These data suggest the involvement of CncR1 in the post-transcriptional modulation of H. pylori motility functions through down-regulation of a critical flagellar checkpoint factor. Concurrently, the cncR1 mutant revealed a decrease of transcript levels for several H. pylori adhesins, resulting in a phenotypically significant impairment of bacterial adhesion to a host gastric cell line. The data presented support a model in which the cag-PAI encoded CncR1 sRNA is able to oppositely modulate bacterial motility and adhesion to host cells.
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Affiliation(s)
- Andrea Vannini
- Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, via Selmi 3, 40126, Bologna, Italy
| | - Davide Roncarati
- Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, via Selmi 3, 40126, Bologna, Italy
| | - Alberto Danielli
- Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, via Selmi 3, 40126, Bologna, Italy.
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Lactobacilli Reduce Helicobacter pylori Attachment to Host Gastric Epithelial Cells by Inhibiting Adhesion Gene Expression. Infect Immun 2016; 84:1526-1535. [PMID: 26930708 DOI: 10.1128/iai.00163-16] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Accepted: 02/25/2016] [Indexed: 02/06/2023] Open
Abstract
The human gastrointestinal tract, including the harsh environment of the stomach, harbors a large variety of bacteria, of which Lactobacillus species are prominent members. The molecular mechanisms by which species of lactobacilli interfere with pathogen colonization are not fully characterized. In this study, we aimed to study the effect of lactobacillus strains upon the initial attachment of Helicobacter pylori to host cells. Here we report a novel mechanism by which lactobacilli inhibit adherence of the gastric pathogen H. pylori In a screen with Lactobacillus isolates, we found that only a few could reduce adherence of H. pylori to gastric epithelial cells. Decreased attachment was not due to competition for space or to lactobacillus-mediated killing of the pathogen. Instead, we show that lactobacilli act on H. pylori directly by an effector molecule that is released into the medium. This effector molecule acts on H. pylori by inhibiting expression of the adhesin-encoding gene sabA Finally, we verified that inhibitory lactobacilli reduced H. pylori colonization in an in vivo model. In conclusion, certain Lactobacillus strains affect pathogen adherence by inhibiting sabA expression and thereby reducing H. pylori binding capacity.
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Tenguria S, Ansari SA, Khan N, Ranjan A, Devi S, Tegtmeyer N, Lind J, Backert S, Ahmed N. Helicobacter pylori cell translocating kinase (CtkA/JHP0940) is pro-apoptotic in mouse macrophages and acts as auto-phosphorylating tyrosine kinase. Int J Med Microbiol 2014; 304:1066-76. [PMID: 25172221 DOI: 10.1016/j.ijmm.2014.07.017] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Revised: 06/26/2014] [Accepted: 07/28/2014] [Indexed: 12/16/2022] Open
Abstract
The Helicobacter pylori gene JHP0940 has been shown to encode a serine/threonine kinase which can induce cytokines in gastric epithelial cells relevant to chronic gastric inflammation. Here we demonstrate that JHP0940 can be secreted by the bacteria, triggers apoptosis in cultured mouse macrophages and acts as an auto-phosphorylating tyrosine kinase. Recombinant JHP0940 protein was found to decrease the viability of RAW264.7 cells (a mouse macrophage cell line) up to 55% within 24h of co-incubation. The decreased cellular viability was due to apoptosis, which was confirmed by TUNEL assay and Fas expression analysis by flow-cytometry. Further, we found that caspase-1 and IL-1beta were activated upon treatment with JHP0940. These results point towards possible action through the host inflammasome. Our in vitro studies using tyrosine kinase assays further demonstrated that JHP0940 acts as auto-phosphorylating tyrosine kinase and induces pro-inflammatory cytokines in RAW264.7 cells. Upon exposure with JHP0940, these cells secreted IL-1beta, TNF-alpha and IL-6, in a dose- and time-dependent manner, as detected by ELISA and transcript profiling by q-RT-PCR. The pro-inflammatory, pro-apoptotic and other regulatory responses triggered by JHP0940 lead to the assumption of its possible role in inducing chronic inflammation for enhanced bacterial persistence and escape from host innate immune responses by apoptosis of macrophages.
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Affiliation(s)
- Shivendra Tenguria
- Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad 500046, India
| | - Suhail A Ansari
- Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad 500046, India
| | - Nooruddin Khan
- Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad 500046, India
| | - Amit Ranjan
- Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad 500046, India
| | - Savita Devi
- Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad 500046, India
| | - Nicole Tegtmeyer
- Division of Microbiology, Department of Biology, Friedrich Alexander University Nuremberg, D-91058 Erlangen, Germany
| | - Judith Lind
- Division of Microbiology, Department of Biology, Friedrich Alexander University Nuremberg, D-91058 Erlangen, Germany
| | - Steffen Backert
- Division of Microbiology, Department of Biology, Friedrich Alexander University Nuremberg, D-91058 Erlangen, Germany
| | - Niyaz Ahmed
- Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad 500046, India.
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Posselt G, Backert S, Wessler S. The functional interplay of Helicobacter pylori factors with gastric epithelial cells induces a multi-step process in pathogenesis. Cell Commun Signal 2013; 11:77. [PMID: 24099599 PMCID: PMC3851490 DOI: 10.1186/1478-811x-11-77] [Citation(s) in RCA: 151] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2013] [Accepted: 10/01/2013] [Indexed: 12/16/2022] Open
Abstract
Infections with the human pathogen Helicobacter pylori (H. pylori) can lead to severe gastric diseases ranging from chronic gastritis and ulceration to neoplastic changes in the stomach. Development and progress of H. pylori-associated disorders are determined by multifarious bacterial factors. Many of them interact directly with host cells or require specific receptors, while others enter the host cytoplasm to derail cellular functions. Several adhesins (e.g. BabA, SabA, AlpA/B, or OipA) establish close contact with the gastric epithelium as an important first step in persistent colonization. Soluble H. pylori factors (e.g. urease, VacA, or HtrA) have been suggested to alter cell survival and intercellular adhesions. Via a type IV secretion system (T4SS), H. pylori also translocates the effector cytotoxin-associated gene A (CagA) and peptidoglycan directly into the host cytoplasm, where cancer- and inflammation-associated signal transduction pathways can be deregulated. Through these manifold possibilities of interaction with host cells, H. pylori interferes with the complex signal transduction networks in its host and mediates a multi-step pathogenesis.
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Affiliation(s)
- Gernot Posselt
- Division of Molecular Biology, Department of Microbiology, Paris-Lodron University, Salzburg, Austria.
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Taghvaei T, Talebi Bezmin Abadi A, Ghasemzadeh A, Naderi BK, Mohabbati Mobarez A. Prevalence of horB gene among the Helicobacter pylori strains isolated from dyspeptic patients: first report from Iran. Intern Emerg Med 2012; 7:505-8. [PMID: 21559747 DOI: 10.1007/s11739-011-0614-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2011] [Accepted: 04/22/2011] [Indexed: 12/12/2022]
Abstract
Helicobacter pylori (H. pylori) is globally accepted as an important cause of gastritis in human, and evidence strongly shows an etiological role for H. pylori in gastric cancer and peptic ulceration. In this study, we determined the relationship between digestive diseases and the horB gene of H. pylori infection. Fresh antral biopsy specimens were obtained from 140 dyspeptic patients (67 men and 73 women; mean age 41.5, aged 19-63 years). They were examined for presence of the horB gene of H. pylori clinical isolates. Bacterial DNA content was extracted directly from the antral biopsy. Statistical analysis was performed with SPSS version 16.0. Prevalence of the horB gene in H. pylori isolated from patients with gastric cancer, gastric ulcer, gastritis and duodenal ulcer is (5/32) 15.6%, (4/25) 16%, (30/43) 70%, and (9/40) 22.5%, respectively. No significant relationship is observed between age, pathologic findings and gender factors with respect to the four digestive diseases (P > 0.05). In our examination, a significant association was observed between a horB positive genotype of H. pylori and the occurrence of gastritis; in support of the protective theory. Studies with a higher sample size in different countries of the world should be conducted to obtain a thorough assessment as to whether horB has a role in the progress of gastritis (protective effect) or not. Further tests should be carried out to determine the exact role of horB in infection of H. pylori.
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Affiliation(s)
- Tarang Taghvaei
- Department of Internal Medicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
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Wang Z, Zhang L, Guo Z, Liu L, Ji J, Zhang J, Chen X, Liu B, Zhang J, Ding Q, Wang X, Zhao W, Zhu Z, Yu Y. A unique feature of iron loss via close adhesion of Helicobacter pylori to host erythrocytes. PLoS One 2012. [PMID: 23185604 PMCID: PMC3503993 DOI: 10.1371/journal.pone.0050314] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Iron deficiency anemia is an extra-stomach disease experienced in H. pylori carriers. Individuals with type A blood are more prone to suffering from H. pylori infection than other individuals. To clarify the molecular mechanisms underlying H. pylori-associated anemia, we collected erythrocytes from A, B, O, and AB blood donors and analyzed morphology, the number of erythrocytes with H. pylori colonies attached to them, and iron contents in erythrocytes and H. pylori (NCTC11637 and SS1 strains) by means of optical microscopy, scanning electron microscopy, and synchrotron radiation soft X-ray imaging. The number of type A erythrocytes with H. pylori attached to them was significantly higher than that of other erythrocytes (P<0.05). Far more iron distribution was observed in H. pylori bacteria using dual energy analysis near the iron L2, 3 edges by soft X-ray imaging. Iron content was significantly reduced in host erythrocytes after 4 hours of exposure to H. pylori. H. pylori are able to adhere more strongly to type A erythrocytes, and this is related to iron shift from the host to the bacteria. This may explain the reasons for refractory iron deficiency anemia and elevated susceptibility to H. pylori infection in individuals with type A blood.
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Affiliation(s)
- Zhiwei Wang
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lijuan Zhang
- Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Science, Shanghai, China
| | - Zhi Guo
- Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Science, Shanghai, China
| | - Lei Liu
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Ji
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jianian Zhang
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xuehua Chen
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bingya Liu
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Zhang
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qiulan Ding
- Department of Transfusion and Clinical Biochemistry, Shanghai Ruijin Hospital, Shanghai, China
| | - Xuefeng Wang
- Department of Transfusion and Clinical Biochemistry, Shanghai Ruijin Hospital, Shanghai, China
| | - Wei Zhao
- Department of Medical Microbiology and Parasitology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhenggang Zhu
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- * E-mail: (YY); (ZZ)
| | - Yingyan Yu
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- * E-mail: (YY); (ZZ)
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13
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Helicobacter pylori AlpA and AlpB bind host laminin and influence gastric inflammation in gerbils. Infect Immun 2011; 79:3106-16. [PMID: 21576328 DOI: 10.1128/iai.01275-10] [Citation(s) in RCA: 86] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Helicobacter pylori persistently colonizes humans, causing gastritis, ulcers, and gastric cancer. Adherence to the gastric epithelium has been shown to enhance inflammation, yet only a few H. pylori adhesins have been paired with targets in host tissue. The alpAB locus has been reported to encode adhesins involved in adherence to human gastric tissue. We report that abrogation of H. pylori AlpA and AlpB reduces binding of H. pylori to laminin while expression of plasmid-borne alpA or alpB confers laminin-binding ability to Escherichia coli. An H. pylori strain lacking only AlpB is also deficient in laminin binding. Thus, we conclude that both AlpA and AlpB contribute to H. pylori laminin binding. Contrary to expectations, the H. pylori SS1 mutant deficient in AlpA and AlpB causes more severe inflammation than the isogenic wild-type strain in gerbils. Identification of laminin as the target of AlpA and AlpB will facilitate future investigations of host-pathogen interactions occurring during H. pylori infection.
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14
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Vermoote M, Vandekerckhove TTM, Flahou B, Pasmans F, Smet A, De Groote D, Van Criekinge W, Ducatelle R, Haesebrouck F. Genome sequence of Helicobacter suis supports its role in gastric pathology. Vet Res 2011; 42:51. [PMID: 21414191 PMCID: PMC3065412 DOI: 10.1186/1297-9716-42-51] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2010] [Accepted: 03/17/2011] [Indexed: 01/14/2023] Open
Abstract
Helicobacter (H.) suis has been associated with chronic gastritis and ulcers of the pars oesophagea in pigs, and with gastritis, peptic ulcer disease and gastric mucosa-associated lymphoid tissue lymphoma in humans. In order to obtain better insight into the genes involved in pathogenicity and in the specific adaptation to the gastric environment of H. suis, a genome analysis was performed of two H. suis strains isolated from the gastric mucosa of swine. Homologs of the vast majority of genes shown to be important for gastric colonization of the human pathogen H. pylori were detected in the H. suis genome. H. suis encodes several putative outer membrane proteins, of which two similar to the H. pylori adhesins HpaA and HorB. H. suis harbours an almost complete comB type IV secretion system and members of the type IV secretion system 3, but lacks most of the genes present in the cag pathogenicity island of H. pylori. Homologs of genes encoding the H. pylori neutrophil-activating protein and γ-glutamyl transpeptidase were identified in H. suis. H. suis also possesses several other presumptive virulence-associated genes, including homologs for mviN, the H. pylori flavodoxin gene, and a homolog of the H. pylori vacuolating cytotoxin A gene. It was concluded that although genes coding for some important virulence factors in H. pylori, such as the cytotoxin-associated protein (CagA), are not detected in the H. suis genome, homologs of other genes associated with colonization and virulence of H. pylori and other bacteria are present.
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Affiliation(s)
- Miet Vermoote
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Tom Theo Marie Vandekerckhove
- Laboratory for Bioinformatics and Computational Genomics, Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium
| | - Bram Flahou
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Frank Pasmans
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Annemieke Smet
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Dominic De Groote
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
| | - Wim Van Criekinge
- Laboratory for Bioinformatics and Computational Genomics, Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium
| | - Richard Ducatelle
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Freddy Haesebrouck
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
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15
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Gilbreath JJ, Cody WL, Merrell DS, Hendrixson DR. Change is good: variations in common biological mechanisms in the epsilonproteobacterial genera Campylobacter and Helicobacter. Microbiol Mol Biol Rev 2011; 75:84-132. [PMID: 21372321 PMCID: PMC3063351 DOI: 10.1128/mmbr.00035-10] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Microbial evolution and subsequent species diversification enable bacterial organisms to perform common biological processes by a variety of means. The epsilonproteobacteria are a diverse class of prokaryotes that thrive in diverse habitats. Many of these environmental niches are labeled as extreme, whereas other niches include various sites within human, animal, and insect hosts. Some epsilonproteobacteria, such as Campylobacter jejuni and Helicobacter pylori, are common pathogens of humans that inhabit specific regions of the gastrointestinal tract. As such, the biological processes of pathogenic Campylobacter and Helicobacter spp. are often modeled after those of common enteric pathogens such as Salmonella spp. and Escherichia coli. While many exquisite biological mechanisms involving biochemical processes, genetic regulatory pathways, and pathogenesis of disease have been elucidated from studies of Salmonella spp. and E. coli, these paradigms often do not apply to the same processes in the epsilonproteobacteria. Instead, these bacteria often display extensive variation in common biological mechanisms relative to those of other prototypical bacteria. In this review, five biological processes of commonly studied model bacterial species are compared to those of the epsilonproteobacteria C. jejuni and H. pylori. Distinct differences in the processes of flagellar biosynthesis, DNA uptake and recombination, iron homeostasis, interaction with epithelial cells, and protein glycosylation are highlighted. Collectively, these studies support a broader view of the vast repertoire of biological mechanisms employed by bacteria and suggest that future studies of the epsilonproteobacteria will continue to provide novel and interesting information regarding prokaryotic cellular biology.
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Affiliation(s)
- Jeremy J. Gilbreath
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390
| | - William L. Cody
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390
| | - D. Scott Merrell
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390
| | - David R. Hendrixson
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390
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Douillard FP, Ryan KA, Lane MC, Caly DL, Moore SA, Penn CW, Hinds J, O'Toole PW. The HP0256 gene product is involved in motility and cell envelope architecture of Helicobacter pylori. BMC Microbiol 2010; 10:106. [PMID: 20377912 PMCID: PMC2864241 DOI: 10.1186/1471-2180-10-106] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2009] [Accepted: 04/08/2010] [Indexed: 11/10/2022] Open
Abstract
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.
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Affiliation(s)
- François P Douillard
- Department of Microbiology & Alimentary Pharmabiotic Centre, University College Cork, Ireland
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Duckworth MJ, Okoli AS, Mendz GL. Novel Helicobacter pylori therapeutic targets: the unusual suspects. Expert Rev Anti Infect Ther 2009; 7:835-67. [PMID: 19735225 DOI: 10.1586/eri.09.61] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Understanding the current status of the discovery and development of anti-Helicobacter therapies requires an overview of the searches for therapeutic targets performed to date. A summary is given of the very substantial body of work conducted in the quest to find Helicobacter pylori genes that could be suitable candidates for therapeutic intervention. The products of most of these genes perform metabolic functions, and others have roles in growth, cell motility and colonization. The genes identified as potential targets have been organized into three categories according to their degree of characterization. A short description and evaluation is provided of the main candidates in each category. Investigations of potential therapeutic targets have generated a wealth of information about the physiology and genetics of H. pylori, and its interactions with the host, but have yielded little by way of new therapies.
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Affiliation(s)
- Megan J Duckworth
- School of Medicine, Sydney, The University of Notre Dame Australia, 160 Oxford Street, Darlinghurst, NSW 2010, Australia.
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Abstract
The clinical outcome of Helicobacter pylori infection is determined by a complex scenario of interactions between the bacterium and the host. The main bacterial factors associated with colonization and pathogenicity comprise outer membrane proteins including BabA, SabA, OipA, AlpA/B, as well as the virulence factors CagA in the cag pathogenicity island (cagPAI) and the vacuolating cytotoxin VacA. The multitude of these proteins and allelic variation makes it extremely difficult to test the contribution of each individual factor. Much effort has been put into identifying the mechanism associated with H. pylori-associated carcinogenesis. Interaction between bacterial factors such as CagA and host signal transduction pathways seems to be critical for mediating the induction of membrane dynamics, actin-cytoskeletal rearrangements and the disruption of cell-to-cell junctions as well as proliferative, pro-inflammatory and antiapoptotic nuclear responses. An animal model using the Mongolian gerbil is a useful system to study the gastric pathology of H. pylori infection.
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Affiliation(s)
- Javier Torres
- Unidad de Investigacion en Enfermedades Infecciosas, UMAE Pediatria, IMSS, Mexico
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Shoaf-Sweeney KD, Hutkins RW. Adherence, anti-adherence, and oligosaccharides preventing pathogens from sticking to the host. ADVANCES IN FOOD AND NUTRITION RESEARCH 2008; 55:101-61. [PMID: 18772103 DOI: 10.1016/s1043-4526(08)00402-6] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
For many pathogenic bacteria, infections are initiated only after the organism has first adhered to the host cell surface. If adherence can be inhibited, then the subsequent infection can also be inhibited. This approach forms the basis of anti-adherence strategies, which have been devised to prevent a variety of bacterial infections. In this chapter, the molecular basis by which respiratory, urinary, and gastrointestinal tract pathogens adhere to host cells will be described. The five general types of anti-adherence agents will also be reviewed. The most well-studied are the receptor analogs, which include oligosaccharides produced synthetically or derived from natural sources, including milk, berries, and other plants. Their ability to inhibit pathogen adherence may lead to development of novel, food-grade anti-infective agents that are inexpensive and safe.
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Affiliation(s)
- Kari D Shoaf-Sweeney
- School of Molecular Biosciences, Washington State University, Pullman, Washington 99164, USA
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