Heliobactor pylori Virulence Factors and Their Role in Pathogenesis
Uniformed Services University Of The Health Sciences Bethesda United States
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Helicobacter pylori is a Gram negative, microaerophilic, spiral shaped bacterium that is the causative agent of a variety of gastric maladies gastritis, peptic ulcers both duodenal and gastric, and two forms of gastric cancer. Currently, several bacterial virulence factors have been associated with more severe gastric disease, including specific polymorphismic forms of two bacterial toxins, CagA and VacA. These toxins have been shown to have numerous effects on host cells, including modulation of multiple cellular pathways that appear to ultimately lead to disease. Through the process of completing this thesis, we were the first group to show an association between East Asian CagA EPIYA-ABD and progression to gastric cancer in a South Korean population. We also examined the role of VacA polymorphisms within that population, and found that while the distribution of vacA alleles was not associated with disease state, it was associated with the distribution of cagA alleles and was integral in a three way interaction with the distribution of cagA alleles and disease state. Next, we analyzed the contribution of the newly described i region of VacA to disease development, and identified an amino acid 196 that was important for the development of gastric cancer. Additionally, we identified some associations that were CagA-dependent, such as the association of VacA and disease state in the EPIYA-ABD population and the association of the distribution of amino acids at position 231 and disease state in the non EPIYAABD population. Moreover, we were able to optimize techniques that will ultimately be used to characterize CagA isogenic strains. Those future studies will serve to define the role of specific EPIYA motifs in H. pylori-induced host cellular damages both in vitro and in vivo.