Helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is though ...

'' virulence factor CagA (cytotoxin-associated gene A) is a 120–145kDa protein encoded on the 40kb ''cag''

pathogenicity island Pathogenicity islands (PAIs), as termed in 1990, are a distinct class of genomic islands acquired by microorganisms through horizontal gene transfer. Pathogenicity islands are found in both animal and plant pathogens. Additionally, PAIs are found i ...

(PAI). ''H. pylori'' strains can be divided into CagA positive or negative strains. Approximately 60% of ''H. pylori'' strains isolated in Western countries carry ''cag'' PAI, whereas almost all of the East Asian isolates are ''cag'' PAI-positive. The ''cag'' PAI also encodes for a

type IV secretion system The bacterial type IV secretion system, also known as the type IV secretion system or the T4SS, is a secretion protein complex found in gram negative bacteria, gram positive bacteria, and archaea. It is able to transport proteins and DNA across t ...

which is used to "inject" CagA into a target cell upon ''H. pylori'' attachment. After translocation, CagA localises to the inner surface of the cell membrane and undergoes tyrosine phosphorylation by

Src family kinase Src kinase family is a family of non-receptor tyrosine kinases that includes nine members: Src, Yes, Fyn, and Fgr, forming the SrcA subfamily, Lck, Hck, Blk, and Lyn in the SrcB subfamily, and Frk in its own subfamily. Frk has homologs i ...

s (e.g.

Fyn Funen ( da, Fyn, ), with an area of , is the third-largest island of Denmark, after Zealand and Vendsyssel-Thy. It is the 165th-largest island in the world. It is located in the central part of the country and has a population of 469,947 as ...

and Lyn).

Role in Cancer

''H. pylori'' infection is associated with

MALT lymphoma MALT lymphoma (MALToma) is a form of lymphoma involving the mucosa-associated lymphoid tissue (MALT), frequently of the stomach, but virtually any mucosal site can be affected. It is a cancer originating from B cells in the marginal zone of the MAL ...

and

gastric adenocarcinoma Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lymph ...

and CagA is thought to be involved in cancer development. Phosphorylated CagA is able to interact with the SHP-2 tyrosine phosphatase, rendering it functionally active, triggering a host cell morphological change to a more motile phenotype known as the "hummingbird phenotype". This phenotype mimics an effect produced by

hepatocyte growth factor Hepatocyte growth factor (HGF) or scatter factor (SF) is a paracrine cellular growth, motility and morphogenic factor. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts o ...

which may participate in various aspects of cancer, including

metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

. CagA is also a highly antigenic protein that is associated with a prominent inflammatory response by eliciting interleukin-8 production.

The ''Cag'' PAI

References

External links

* {{cite web , title=Search: "cytotoxin-associated gene A" "Helicobacter pylori" , work=Protein , publisher=NCBI , url=https://www.ncbi.nlm.nih.gov/protein/?term=%22cytotoxin-associated+gene+A%22+%22Helicobacter+pylori%22 Virulence factors Helicobacter pylori Infectious causes of cancer