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The cag Pathogenicity Island.


In: Mobley HLT, Mendz GL, Hazell SL, editors.


Helicobacter pylori: Physiology and Genetics. Washington (DC): ASM Press; 2001. Chapter 31.


The function of the cag PAI in H. pylori-associated disease has been the subject of controversy ever since its discovery in 1993. Clinical studies with different outcomes have been performed to test whether the presence of the cag PAI is connected with peptic ulcer disease or gastric cancer. Often these studies were based on PCR amplifications of the cagA gene, which was used as a marker for the cag PAI. In some of these studies, clear proof of the involvement of cag in severe forms of gastric diseases often was not provided. The problem in some of these studies was that cag was examined as a static DNA region (cagA present or not) rather than as a DNA sequence encoding a sophisticated secretion apparatus with the function of injecting virulence factors into the host cell (Fig. 4). The work of various laboratories during the past year therefore has provided better insight into the biological complexity of H. pylori-host interactions and the molecular function of the cag PAI in pathogenesis. Future approaches have to consider that the presence of the cagA gene alone is not equal to virulence. A single point mutation anywhere in the 40-kbp region may abolish the function of the type IV secretion system and CagA transloction into the host cell (Fig. 4). We may assume that the majority of type I strains are de facto less virulent due to an abrogated function of the secretion system or of the cagA gene. Additionally, we have to consider that bacteria are just one term of the equation. No matter how many virulence factors they possess, the host has receptors and targets for these factors and allelic polymorphism may dictate resistance. If we restrict our attention to the group of patients with peptic ulcer disease and who are infected with H. pylori, we will find that more than 90% of the individuals carry type I strains. On the basis of the nature of the cag-encoded factors, it is most likely that the translocation of virulence proteins including CagA through the type IV secretion system is one important molecular mechanism by which H. pylori can, in the long term, influence the clinical outcome of the infection.

Copyright © 2001, ASM Press.

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