Category Archives: Cag PAI

Summary

Similar to the cag PAI, this region displays a lower guanine and cytosine content than the rest of the genome, suggesting this region may also contain horizontally acquired PAIs. Knowledge of the genes encoded within the plasticity region is limited but growing. Genes coding for proteins with homology to type IV secretion system components unique from those encoded on the cag PAI have been localized to the plasticity region. A gene of unknown function found in the plasticity region, named JHP947, may be associated with duodenal ulcer and gastric cancer.

Cag PAI (5)

There are also instances whereby functional effects have yet to be associated with a specific bacterial factor, such as suppression of IL-4-induced signal transduction by H pylori infection, indicating a need for more work in the signal transduction area. Future directions should employ multiple experimental techniques to characterize signalling pathways and functional outcomes modulated by H pylori infection. For example, signature tagged mutagenesis could reveal which H pylori genes are important during infection in vivo.

Cag PAI (4)

Interestingly, the number of tyrosine residues on which CagA can be phosphorylated shows variation among strains, and more phosphorylation sites lead to increased CagA biological activity and association with disease. Functionally, CagA is implicated in cytoskeletal rearrangements through binding Src homology-2-containing phosphatase and dephosphorylation of host cell cytoskeletal proteins. CagA also binds to tight junction proteins, including zonula occludens 1 and junctional adhesion molecule to increase paracellular permeability of an epithelial monolayer.

Cag PAI (3)

While understanding of CagA is improving, our knowledge of other Cag proteins is minimal. For example, CagF associates with the bacterial outer membrane and induces an antibody response from infected humans, but its precise function remains unknown. Isogenic mutants lacking CagG, CagL, CagH, CagI or CagM all show a reduced capacity to stimulate DNA-binding activity of the host cell transcription factor AP-1 compared with the wild-type strain.

Cag PAI (2)

The precise functions of genes encoded on the cag PAI remains incompletely characterized. Deletion of the cag PAI reduces the ability of H pylori to induce IL-8 secretion from host cells . Some genes on the cag PAI also show similarity to known genes in Agrobacterium tumefaciens that encode a type IV secretion system , which is a filamentous bacterial surface appendage that can breach the host cell membrane to inject bacterial proteins.

Cag PAI (1)

Sequencing of the H pylori genome in 1997 facilitated a closer look at the cag PAI, an approximately 40 kb segment of DNA integrated into the H pylori chromosome that encodes about 30 genes . This PAI likely was acquired by horizontal transfer, as indicated by a guanine and cytosine content that is different from the remainder of the bacterial genome (35% versus 39% ) and by the transposable elements that flank its sequence . It is present only in some H pylori strains and, thus, serves as a marker to classify strains, whereby type I strains carry the cag PAI and type II strains do not.