H. pylori Virulence Factors
Lyudmila Boyanova
from: Helicobacter pylori (Edited by: Lyudmila Boyanova). Caister Academic Press, U.K. (2011)
Abstract
H. pylori infection outcomes strongly depend on the strain virulence. H. pylori displays enormous genetic diversity by frequent mutations, intra- or intergenomic recombinations and natural transformation, and additional phase variations by slipped-strand mispairing. H. pylori spiral shape, urease, motility, lipopolysaccharide (LPS) and outer membrane adhesins enable the establishment of the infection. H. pylori genetic diversity and induced immunomodulation contribute to the infection chronicity. Prevalence of virulence factors varies according to the patient disease, ethnicity, age and country. H. pylori VacA causes vacuolation, pore formation, disruption of endo-lysosomal activity, apoptosis in gastric cells and immunomodulation. CagA oncoprotein alters cell-signalling pathways and induces morphological changes, chromosomal instability, cell proliferation and apoptosis, interleukin (IL)-8 release and proto-oncogene activation. CagA type D EPIYA and increased number of C repeats have been linked to increased SHP-2 phosphatase activity and hence high risk for gastric cancer. In East Asia, nearly all strains have been highly virulent, carrying intact cagPAI, East Asian CagA and vacA s1/i1/m1 type, which can help to explain the high gastric cancer incidence there. Although the infection outcomes have shown strong association with cagA, cagPAI and vacA status of the strains, mainly in Western countries, the combined activity of all H. pylori virulence factors, involving also dupA, oipA, iceA, homB, babA, sabA, hopQ and other genes/gene status appears to be crucial for the infection pathogenesis. Tipα protein, HP-NAP, heat-shock-proteins, LPS mimicry and interaction with toll-like receptors influence the infection course as well. By the complex and well-coordinated interplay of its virulence factors, H. pylori adapts to the changing environment and can either increase or suppress the gastric inflammation. Moreover, microevolution of the virulence genes emerges in the individual patient over years. Briefly, the direct effects of H. pylori virulence factors and the chronic gastric inflammation can lead to the development of peptic ulcers or malignancy. Targeting the virulent strains in a country or region is important to explain better the clinical significance of some virulence factors and their interaction, to choose local diagnostic markers, to imply aggressive eradication strategies in the concerned patients and to provide new agents and improved regimens to control the infection read more ...
