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Characterization of the Helicobacter pylori Nitric Oxide Induced Outer Membrane Protein Gene, hofD
Horner, Jessica Lynn
Horner, Jessica Lynn
Abstract
Helicobacter pylori is a human stomach pathogen associated with the development of both peptic ulcers and gastric cancer. It infects about 50% of the world’s population and disproportionately impacts developing nations. To initiate infection, H. pylori needs to withstand the hostile gastric environment. Stomach acid and host immune responses normally kill pathogens. Conversely, these signals trigger expression of genes in H. pylori and allow for it to colonize. H. pylori senses environmental changes in the stomach because it utilizes Two Component Systems (TCS). CrdRS is a TCS that senses and responds to nitric oxide. HofD, a relatively uncharacterized outer membrane protein, was demonstrated to be triggered by nitric oxide in a CrdRS dependent manner by previous studies conducted in our lab. Nitric oxide (NO) is an innate human immune response to limit pathogen growth. This project focused on HofD and explored its behavior in both NO environments and in vitro infection models. By creating mutant strains of H. pylori, including 26695 ∆hofD and 26695 hofD-Flag, the function of HofD was elucidated using an assortment of bioassays. Experiments using AGS gastric cancer cells demonstrated the ability of HofD to modulate H. pylori adherence to the gastric epithelium. ELISA assays subsequently demonstrated this modified adherence significantly affected subsequent secretion of the proinflammatory cytokine, IL-8. This novel information provides insight into H. pylori pathogenesis and may assist in the development of new clinical treatments, which is especially important as antibiotic resistance continues to develop in H. pylori infection.
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2024-04-01
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Biology