Translocation of the Helicobacter pylori CagA protein in gastric epithelial cells by a type IV secretion apparatus

Backert, Steffen; Ziska, Elke; Brinkmann, Volker; Zimny‐Arndt, Ursula; Fauconnier, A; Jungblut, Peter P.R.; Naumann, Michael; Meyer, Thomas F.

doi:10.1046/j.1462-5822.2000.00043.x

Cited by 384 publications

(344 citation statements)

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“…In parallel, studies by several laboratories are generating extensive information about the cellular consequences of CagA translocation. On transfer, CagA localizes on the inner surface of the plasma membrane where it interacts with and is phosphorylated by the Src family of protein tyrosine kinases, such as c-Src [84][85][86][87][88][89][90][91] . The CagA phosphorylation sites have been mapped to the so-called EPIYA motifs that share homology with c-Src consensus phosphorylation sites and are present in variable numbers in the carboxy-terminal half of the protein 89,91 .…”

Section: H Pylori Caga Transfermentioning

confidence: 99%

The versatile bacterial type IV secretion systems

Cascales¹,

Christie²

2003

Nat Rev Microbiol

597

559

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Bacteria use type IV secretion systems for two fundamental objectives related to pathogenesisgenetic exchange and the delivery of effector molecules to eukaryotic target cells. Whereas gene acquisition is an important adaptive mechanism that enables pathogens to cope with a changing environment during invasion of the host, interactions between effector and host molecules can suppress defence mechanisms, facilitate intracellular growth and even induce the synthesis of nutrients that are beneficial to bacterial colonization. Rapid progress has been made towards defining the structures and functions of type IV secretion machines, identifying the effector molecules, and elucidating the mechanisms by which the translocated effectors subvert eukaryotic cellular processes during infection. The year 2003 marks the fiftieth anniversary of the first description of a TYPE IV SECRETION (T4S)SYSTEM: the CONJUGATION apparatus of the F plasmid 1 . This is a dynamic bacterial surface organelle, the activities of which are now known to include the contact-dependent delivery of DNA to bacterial recipients and the assembly and retraction of a conjugal PILUS 2 . In the past decade, reports describing systems that are ancestrally related to the F-transfer system and other conjugation machines have emerged. Instead of mediating DNA transfer between bacteria, these systems deliver DNA or protein substrates, known as effectors, to eukaryotic target cells during infection [3][4][5] . More recently, several new T4S systems have been described that are also ancestrally related to the conjugation machines, but these systems mediate the exchange of DNA with the extracellular milieu [6][7][8] . Collectively, this diversity of function in the face of a common ancestry makes the T4S machines attractive subjects for comparative studies that explore the dynamics of organelle assembly and action. Additionally, from a medical perspective, it is of enormous interest to develop a detailed understanding of how the inter-kingdom transfer of type IV effector molecules contributes to pathogenesis. This review will summarize the recent advances in our knowledge of T4S, NIH Public Access Author ManuscriptNat Rev Microbiol. Author manuscript; available in PMC 2013 December 27. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscriptwith an emphasis on machine structure and function, and the activities of effectors after translocation into the eukaryotic host. The T4S familyThis fascinatingly versatile translocation family can be classified into three subfamilies, each of which contributes in unique ways to pathogenesis ( Fig. 1; Table 1). The largest subfamily, the conjugation systems, are found in most species of Gram-negative and Grampositive bacteria. These systems mediate DNA transfer both within and between phylogenetically diverse species, and some systems even deliver DNA to fungi, plants and human cells 2,9-13 . Conjugation is an important contributor to genome plasticity, and therefore bacterial fitness under changing en...

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Section: H Pylori Caga Transfermentioning

confidence: 99%

The versatile bacterial type IV secretion systems

Cascales¹,

Christie²

2003

Nat Rev Microbiol

597

559

View full text Add to dashboard Cite

show abstract

“…Following the attachment of cagA-positive H. pylori to the surface of gastric epithelial cells, CagA is delivered from the bacterium into the cytoplasm of host cells through the type IV secretion system (Segal et al, 1999;Asahi et al, 2000;Backert et al, 2000;Odenbreit et al, 2000;Stein et al, 2000). This process is mediated at least partly through an interaction of H. pylori CagL with integrins (Kwok et al, 2007).…”

Section: Translocation Of H Pylori Caga Into Gastric Epithelial Cellsmentioning

confidence: 99%

Linking epithelial polarity and carcinogenesis by multitasking Helicobacter pylori virulence factor CagA

Hatakeyama

2008

Oncogene

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“…Its genome contains a cagpathogenicity island (cagPAI), encoding proteins for a specialized type IV secretion system (T4SS), which injects virulence factors directly into the host cytoplasm of infected epithelial cells. So far, peptidoglycans (Viala et al, 2004) and the CagA protein (Asahi et al, 2000;Backert et al, 2000;Odenbreit et al, 2000;Stein et al, 2000) are known to translocate into the infected epithelial host cell. Translocated CagA induces cellular processes, which lead to stimulation of cell dissemination followed by cell motility, and invasive growth in gastric epithelial cells (Segal et al, 1999;Bagnoli et al, 2005).…”

Section: Introductionmentioning

confidence: 99%