Helicobacter pylori exploits human CEACAMs via HopQ for adherence and translocation of CagA

Königer, Verena; Holsten, Lea; Harrison, Ute; Busch, Benjamin; Loell, Eva; Zhao, Qing; Bonsor, Daniel A.; Roth, Alexandra; Tchoupa, Arnaud Kengmo; Smith, Stella I.; Mueller, Susanna; Sundberg, Eric J.; Zimmermann, Wolfgang; Fischer, Wolfgang; Hauck, Christof R.; Haas, Rainer

doi:10.1038/nmicrobiol.2016.188

Cited by 148 publications

(180 citation statements)

References 38 publications

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“…Based on the crystal structure of the extracellular domain of HopQ, a β-hairpin insertion in the extracellular 3 + 4 helix bundle domain of HopQ is important for CEACAM binding, and this determines the type of HopQ allele. A peptide derived from this domain competitively inhibits HopQ-mediated Cag translocation, similar to that observed with genetic or antibody-mediated abrogation of HopQ function [53,54]. This suggests the possibility that CagA translocation is mediated not only by the T4SS, but also by membrane proteins (Figure 1).…”

Section: Hopqsupporting

confidence: 64%

Helicobacter pylori Outer Membrane Protein-Related Pathogenesis

Matsuo

Kido

Yamaoka

2017

Toxins

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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.

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Section: Hopqsupporting

confidence: 64%

Helicobacter pylori Outer Membrane Protein-Related Pathogenesis

Matsuo

Kido

Yamaoka

2017

Toxins

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“…The Hop family includes adhesins the blood group antigen binding adhesin (BabA), the sialic acid-binding adhesin (SabA), the adherence-associated lipoproteins A and B (AlpA and AlpB), HopZ, HopQ, outer inflammatory protein (OipA) and five Hop porins [47,48]. HopQ binds to the carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) 1, 3, 5 and 6 on the host cell surface, which strongly supports H. pylori adherence and can potentiate thereby T4SS function [48,49,50]. OipA can activate NF-κB in gastric epithelial cells cag PAI-independently [51].…”

Section: Infections and Nf-κb Regulation In Gastric Mucosamentioning

confidence: 99%

NF‐κB Signaling in Gastric Cancer

Sokolova

Naumann

2017

Toxins

182

122

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Gastric cancer is a leading cause of cancer death worldwide. Diet, obesity, smoking and chronic infections, especially with Helicobacter pylori, contribute to stomach cancer development. H. pylori possesses a variety of virulence factors including encoded factors from the cytotoxin-associated gene pathogenicity island (cagPAI) or vacuolating cytotoxin A (VacA). Most of the cagPAI-encoded products form a type 4 secretion system (T4SS), a pilus-like macromolecular transporter, which translocates CagA into the cytoplasm of the host cell. Only H. pylori strains carrying the cagPAI induce the transcription factor NF-κB, but CagA and VacA are dispensable for direct NF-κB activation. NF-κB-driven gene products include cytokines/chemokines, growth factors, anti-apoptotic factors, angiogenesis regulators and metalloproteinases. Many of the genes transcribed by NF-κB promote gastric carcinogenesis. Since it has been shown that chemotherapy-caused cellular stress could elicit activation of the survival factor NF-κB, which leads to acquisition of chemoresistance, the NF-κB system is recommended for therapeutic targeting. Research is motivated for further search of predisposing conditions, diagnostic markers and efficient drugs to improve significantly the overall survival of patients. In this review, we provide an overview about mechanisms and consequences of NF-κB activation in gastric mucosa in order to understand the role of NF-κB in gastric carcinogenesis.

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“…[30, 31] Furthermore, H. pylori is also known to gain adhesion through defined members of the carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) on gastric epithelial cells via HopQ for adherence and subsequent translocation of cytotoxin-associated gene A (CagA) for virulence. [32] …”

Section: Introductionmentioning

confidence: 99%

Coating Nanoparticles with Gastric Epithelial Cell Membrane for Targeted Antibiotic Delivery against Helicobacter pylori Infection

Angsantikul

Thamphiwatana

Zhang

et al. 2018

Advanced Therapeutics

127

103

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Inspired by the natural pathogen-host interactions and adhesion, this study reports on the development of a novel targeted nanotherapeutics for the treatment of Helicobacter pylori (H. pylori) infection. Specifically, plasma membranes of gastric epithelial cells (e.g. AGS cells) are collected and coated onto antibiotic-loaded polymeric cores, the resulting biomimetic nanoparticles (denoted AGS-NPs) bear the same surface antigens as the source AGS cells and thus have inherent adhesion to H. pylori bacteria. When incubated with H. pylori bacteria in vitro, the AGS-NPs preferentially accumulate on the bacterial surfaces. Using clarithromycin (CLR) as a model antibiotic and a mouse model of H. pylori infection, the CLR-loaded AGS-NPs demonstrate superior therapeutic efficacy as compared the free drug counterpart as well as non-targeted nanoparticle control group. Overall, this work illustrates the promise and strength of using natural host cell membranes to functionalize drug nanocarriers for targeted drug delivery to pathogens that colonize on the host cells. As host-pathogen adhesion represents a common biological event for various types of pathogenic bacteria, the bioinspired nanotherapeutic strategy reported here represents a versatile delivery platform that may be applied to treat numerous infectious diseases.

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Helicobacter pylori exploits human CEACAMs via HopQ for adherence and translocation of CagA

Cited by 148 publications

References 38 publications

Helicobacter pylori Outer Membrane Protein-Related Pathogenesis

Helicobacter pylori Outer Membrane Protein-Related Pathogenesis

NF‐κB Signaling in Gastric Cancer

Coating Nanoparticles with Gastric Epithelial Cell Membrane for Targeted Antibiotic Delivery against Helicobacter pylori Infection

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