ArticleInfection and immunity2002
Functional analysis of the Helicobacter pylori cag pathogenicity island reveals both VirD4-CagA-dependent and VirD4-CagA-independent mechanisms.
Article in Infection and immunity, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed.
- Deciphering the initiation pathway of CagT4SS assembly by in vitro reconstitution of subcomplexes.Nature communications · 2026Article
- A vicious cycle inducer in gastric pathogenesis: implication of Helicobacter pylori.Archives of microbiology · 2026Review
- Infection and herbicide exposure implicate c-Abl kinase in α-Synuclein Ser129 phosphorylation.Cell communication and signaling : CCS · 2025Article
- Whole-Genome Sequencing and Phenotypic Analysis ofMicroorganisms · 2024Article
- Genetic diversity of Helicobacter pylori type IV secretion system cagI and cagN genes and their association with clinical diseases.Scientific reports · 2023Article
- Helicobacter pylori CagA oncoprotein interacts with SHIP2 to increase its delivery into gastric epithelial cells.Cancer science · 2020Article
- Oral and intestinal bacterial exotoxins: Potential linked to carcinogenesis.Progress in molecular biology and translational science · 2020Review
- Anti-Laboratory animal research · 2020Article
- Tailor-Made Detection of Individual Phosphorylated and Non-Phosphorylated EPIYA-Motifs ofCancers · 2019Article
- Fragment-based screening identifies inhibitors of ATPase activity and of hexamer formation of Cagα from the Helicobacter pylori type IV secretion system.Scientific reports · 2019Article
- α-Difluoromethylornithine reduces gastric carcinogenesis by causing mutations inProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Cot kinase plays a critical role in Helicobacter pylori-induced IL-8 expression.Journal of microbiology (Seoul, Korea) · 2017Article
- Genetic variants ofGut pathogens · 2017Article
- Article
- A C-Terminal Coiled-Coil Region of CagL is Responsible forEuropean journal of microbiology & immunology · 2016Article
- The Helicobacter pylori cytotoxin CagA is essential for suppressing host heat shock protein expression.Cell stress & chaperones · 2016Article
- Article
- Roles of the Putative Type IV-like Secretion System Key Component VirD4 and PrsA in Pathogenesis ofFrontiers in cellular and infection microbiology · 2016Article
- Expression of cagA, virB/D Complex and/or vacA Genes in Helicobacter pylori Strains Originating from Patients with Gastric Diseases.PloS one · 2016Article
- Article
8 more citing papers are in PubMed but not listed here.
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4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The type IV secretion machinery encoded by the cag pathogenicity island (PAI) of Helicobacter pylori has been implicated in a series of host responses during infection. Here, we analyzed the function of 12 cag PAI genes from both cag I and cag II loci, including the complete virB/D complex (virB4, virB7, virB8, virB9, virB10, virB11, and virD4). We monitored interleukin-8 (IL-8) secretion, CagA translocation and tyrosine phosphorylation, and induction of a scattering ("hummingbird") phenotype upon H. pylori infection of AGS gastric epithelial cells. For the first time, we have complemented individual cag PAI gene knockout mutants with their intact genes expressed from a shuttle vector and showed that complemented CagA and VirD4 restored wild-type function. Our results demonstrate that phenotypic changes and phosphorylation of CagA depended on all virB/D genes and several other genes of the cag PAI. Induction of IL-8 secretion depended largely on the same set of genes but was independent of CagA and VirD4. Thus, CagA translocation and induction of IL-8 secretion are regulated by VirD4-CagA-dependent and VirD4-CagA-independent mechanisms, respectively. The function of VirD4 as a possible adapter protein which guides CagA into the type IV secretion channel is presented in a model.
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